Paper - Growth of the human prenatal hypophysis and the hypophyseal fossa

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Covell WP. Growth of the human prenatal hypophysis and the hypophyseal fossa. (1927)

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This historic 1927 paper by Covell describes pituitary and the surrounding fossa development in the human embryo. Amer. J Anat. 38(I): 379- Modern Notes: See pages Pituitary Development Endocrine Links: Introduction | BGD Lecture | Science Lecture | Lecture Movie | pineal | hypothalamus‎ | pituitary | thyroid | parathyroid | thymus | pancreas | adrenal | endocrine gonad‎ | endocrine placenta | other tissues | Stage 22 | endocrine abnormalities | Hormones | Category:Endocrine Historic Embryology - Endocrine   1903 Islets of Langerhans | 1903 Pig Adrenal | 1904 interstitial Cells | 1908 Pancreas Different Species | 1908 Pituitary | 1908 Pituitary histology | 1911 Rathke's pouch | 1912 Suprarenal Bodies | 1914 Suprarenal Organs | 1915 Pharynx | 1916 Thyroid | 1918 Rabbit Hypophysis | 1920 Adrenal | 1935 Mammalian Hypophysis | 1926 Human Hypophysis | 1927 Adrenal | 1927 Hypophyseal fossa | 1930 Adrenal | 1932 Pineal Gland and Cysts | 1935 Hypophysis | 1935 Pineal | 1937 Pineal | 1935 Parathyroid | 1940 Adrenal | 1941 Thyroid | 1950 Thyroid Parathyroid Thymus | 1957 Adrenal

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Growth of the Human Prenatal Hypophysis and the Hypophyseal Fossa

W. P. Covell

Department of Anatomy, Universityof Minnesota

Twenty-One Figures

Introduction

For the most part, morphologic observations on the hypophysis have been confined to qualitative studies of its structure and development. Quantitative data comprise but an exceedingly small portion of the principal contributions to our general knowledge of this gland.

The literature dealing with the dimensional growth of the prenatal gland and its fossa is scanty, as may be seen from the following brief review bearing on the stages involved in this study.

Schoneman (’92), from a study of six apparently normal newborn hypopliyses, determined the weight of the gland as 0.13 gram for the newborn. Comte (’98) found the weights for five glands from postnatal material ranging in age from ten days to five mo11tl1s to average 0.113 gram. Thelrange in weight of the glands was 0.095 to 0.125 gram. Cutore (’10) gives the weights of three hypophyses from fetuses measuring from 49.5 to 52 cm. in total body length. He found the weight of one newborn specimen to be 0.032 gram, tl1e remaining two (of 50 and 52 cm. in body length) were 0.10 gram each.

Among the data collected by Parski (’01) are to be found the weights of three glands from fetuses of about the fifth fetal month. The average weight for the two of 26 cm. total body length he gives as 0.018 gram and the weight of the gland of a fetus of 30 cm. as 0.012 gram. He found the weights of five hypophyses from fetuses measuring about 50 em. in body length to range from 0.05 to 0.1 gram. In four infants averaging 57 cm. in total body length he found the range in gland weight to be between 0.06 and 0.1 gram. ‘

Lucien (’11) described the hypophysis as having a weight of approximately 0.1 gram at birth and as representing 1/44994 of the total body weight in males, from birth to five years of age, and 1/3252 for females of the same range of age. He found the diameters of the gland in the course of the first year of life to be 0.9 cm. transversely, 0.6 cm. a11teroposteri— orly, by 0.4 em. vertically. He conceived of the idea of representing the volume of the hypophysis i11 terms of an ellipsoid form by use of the three diameters in the equation for determining the volume of an ellipse. He found the V-olume in cubic centimeters to be approximated by the following formula:

Transverse >< Antcropostcrior >< Vertical " 0’ 1.91

The computed volume of the hypophysis of a newborn, accord ing to him, is 0.12 cc. GROWTH or HUMAN PRENATAL HYP()PHYSIS 381

Thom (’01) described the average diameters of the anterior lobe for the neonatal period as 6.75 mm. transversely, 3 mm. sagittally, and 2.5 mm. vertically. In o11e instance of a six months’ postnatal male he found the diameters to be 8 mm. transversely, 3 mm. sagittally (-1.0 mm., including the pars nervosa), and 3 mm. vertically. According to his findings, the average diameters of the gland for the first year of life are 7.35 mm. transversely, 4.11 mm. sagittally, and 2.46 mm. vertically.

I wish to express my appreciation to Prof. A. T. Rasmussen and Prof. R. E. Scammon for their valuable aid and suggestions during the course of the present study.

Material and Methods

The material used in this study consisted of ninety—eight specimens of the hypophysis of prenatal life and fifty of the hypophyseal fossa. The fetuses were of the Caucasian race and for the most part of Scandinavian-American parentage. Eighty—two of the hypophyses were from fetuses ranging in crown-heel dimension from 15 to 55 cm. and sixteen were from material of 1.1 to 15 cm., crown-rump. Of the sixteen specimens, which represent the earlier stages of prenatal development, eight were from slides of the embryos in the collection of the Department of Anatomy, University of Minnesota. The remaining eight were from material which had been previously preserved in 10 per cent formalin for some time. Thirty-six of the eighty-two hypophyses of fetal life were from material which had been similarly treated. The remaining forty-six were from autopsied material of the Department of Pathology of the University of l\[innesota and a division of the Children’s Bureau of the Department of Labor, Washington, D. (1., under the supervision of Dr. F. L. Adair. The fresh glands were fixed in about 33 per cent formalin neutralized with magnesium carbonate, in which they were allowed to remain from four days to one week.

In order to avoid injury to the gland, it was found necessary to remove the whole sella turcica and so leave the hypophysis intact in its fossa. Such a procedure was followed for both fresh and preserved material.

After removal of the sella turcica, with the hypophysis in situ, it was placed in the neutral formalin and the gland later dissected out. This method has been found by Rasmussen and Herrick ( ’22) to be the most satisfactory procedure, since the posterior lobe is too easily injured if an attempt is made to dissect out the gland from its fossa before fixation. Such a treatment of the material is also advantageous for a closer approximation of the true diameters of the hypophysis.

In dissecting out the hypophysis from the hypopliyseal fossa, the dural sheath was first loosened and taken off. After the gland had been removed from the fossa, the infundibular stalk was then cut close to the body of the hypophysis. The organ was then returned to neutral formalin and allowed to remain for a day or'so longer, i11 order to give ample time for fixation.

Methods of ('0lIc(‘ti1i2g data

Before weigliiiig the gland the excess fluid was blotted off b_v g'e11tly rolling it over on filter—paper. It was then placed in a moist chamber and readings taken to one—tenth of a milligram 011 an analytical balance. Three lineal measurements wore then made on each hypophysis by means of steel Vernier calipers which could be read to one—tenth of a millimeter. Similarly, measurements were recorded on the length, breadth, and depth of the hypophyseal fossa.

The hypophysis was then dehydrated in the usual manner, cleared in Xylol, and embedded in 55° paraflin after four to five hours in the paraffin oven. Horizontal sections of 10 ii in thickness were cut a11d arranged serially. At intervals of about one—fourth, one-half, and three-fourths of the way resented every tenth section intermediate between the sections were made.. Every tenth section and in some instances every fifth section of the series was mounted. For some of GROWTH or HUMAN PRENATAL HYPOPHYSIS 383

the glands two sets of slides were made. The second set represented every tenth section intermediate between the sections of the first series. The mounted sections were usually stained in l\[allory’s triple connective-tissue stain (acid fuchsin, aniline blue, and orange G). A few series were stained in Delafield’s hematoxylin and eosin. The stained sections were then dehydrated, cleared in xylol, and mounted in balsam.

In order to ascertain the relative volume of each of the lobes, the method used by Hammar (’14), Jackson (’17), and Rasmussen and Herrick (’22) was followed. Every mounted section of the 10 u series was projected, by means of an Edinger projection apparatus, onto paper of standard weight (about 0.012 gram per 1 sq.cm.). A magnification of about forty times was used for the glands from fetuses of the latter half of the fetal period. This was increased to 75 or 100 times for the material of early prenatal life. The areas of the lobes were then outlined by means of a sharp hard pencil.

The outlined areas were then cut out with a small pair of scissors and the various parts weighed. The relative proportion which each lobe forms of the total paper weight is then comparable to that of the fresh gland, providing the shrinkage of each lobe has been about the same. Jackson (’17) and Rasmussen and Herrick (’22) found sufficiently close agreement between the glandular and neural portions in this re— spect. The relative weight of each lobe was determined by dividing the total paper weight of each lobe by the sum of the paper weights for the three lobes. It was then possible to ascertain the absolute weight of each of the lobes from the original as recorded before embedding.

For the embryonic and early fetal material, the hypophysis was treated in the above manner, with the exception of a higher magnification (75 or 100 times) and the projection of every section. In most of this material it was necessary to obtain an approximation of the weight of the gland from the total paper weight, since the weight before fixation was not obtainable. For such a determination it was necessary to 384 w. P. cov ELL

approximate the relative amount of shrinkage due to the process of embedding. This was done by taking measurements on a ‘small part of the body on the drawings (made to scale) filed in the collection. These measurements were compared with measurements made on the same part after it l1ad been embedded, sectioned, stained, and mounted. From the serial sections the weight of the gland was then obtained by dividing the total paper weight by the weight of 1 sq.cm. of paper, then further dividing by the magnification squared, multiplying the result by the thickness of the section (reduced to centimeters), and finally correcting for the amount of shrinkage and multiplying by the specific gravity of 1.066 (Vierordt, ’06).

Methods of n'cafmc17,t of the data

In order to show the changes which occur i11 the hypophysis, the data approximating the growth changes in weight and lineal dimensions of the hypophysis and diameters of the hypophyseal fossa were treated by graphic and analytical methods. In this analysis the following steps were taken: 1) (.‘onstruction of graphs with the individual cases and average points plotted. 2) Fitting the data to empirical formulae based on body length. 3) Making tables for comparison of the observed and calculated values for 5-cm. intervals of crown-heel or total body length. Tables and a histogram were compiled to show the relative volumes of the three lobes of the hypophysis in terms of the body length. Other tables and curves were made to illustrate the approximate percentage growth of the gland and its fossa in prenatal life.

(l«)~22.s*t1"2¢(:t27()2z. of _(;mph.s*. Total or crown—heel body length in centimeters formed the abscissae of each graph, while the weight or dimension of the specimen or its part formed the ordinates. Average points were plotted on the basis of means of values for 2.5—cm. intervals of crown-heel or total bod_v length.

Iu’cpr(3.s‘c12t(Lti072 of data by cmpz7rical fomnulac. The empirical formulae used for expressing the growth changes in volume and linear measurements were of three different sorts. The method of approximation employed for the observed values was the method of averages. The lineal dimensions of the hypophysis and the hypophyseal fossa when plotted ac« cording to the crown—heel measurement were found to be approximately expressed by the straight—1ine formula: Y :: aX + b. \Vhere Y is the value to be determined in centimeters, X is the body length i11 decimeters, and a and I) are constants which are empirically determined.

The formulae for the expression of weight of the gland and its parts, with the exception of the pars nervosa, during prenatal life have been represented by the following general for— mula: Y: aX". VVhere Y is the value in question expressed i11 milligrams, X is the crown—hecl or total body length in centimeters or decimeters, and a and I) are the empirically determined constants, a being a decimal fraction and I) a power. In its logarithmic form the formula reads: Log Y-.:log a + b log X. Thus the plot of log Y against log X approximates a straight line.

The growth of the pars nervosa of the hypophysis, in fetuses ranging from 15 to 55 cm. in total body length, was found to be more readily approximated by means of the following formula: Y = ae"X. VVhere Y is the val11e to be determined in milligrams, a and b are constants to be empirically determined, e is the base of natural (napierian) logarithms, and X is the cr0wn~heel or total body length in decimeters. In this equation the plot of log Y against X approximates a straight line and the logarithmic expression of the formula is the following: Log Y :log a + (b log e) X.

An example of the method. The three types of empirical formulae used for expressing i11 numerical terms the growth of the prenatal hypophysis and its fossa are listed above. The type of formula used for approximating the growth of the li11eal dimensions may be expressed as follows: Y = aX -1- b. In order to develop an expression of this kind from the ob served data, the method of averages was used. This is described by Lipka (’18). 386 W. P. COVELL

Using the data on the transverse diameter of the fossa, Y is then the diameter in millimeters, X is the crown-heel measurement in decimeters a11d a and I) are constants to be determined by this method. The following data given in the table below are the observed values for total body length and for the transverse diameter of the fossa.

CRowN_HEEL '1‘R.-\Ns\'ERSF. DIA.‘[lE”l‘F.R OF

THE 1-{YPOPH\‘s1-:.\l. 1-‘oss.\ Range Mean Mean dm. rim. mm. 2.0 to 2.5 2.35 5.26 2.5 to 3.0 2.77 5.53 3.0 to 3.5 3.29 6.40 3.5 T0 -1.0 3.77 6.93 4.0 to 4.5 4.16 7.35 4.5 to 5.0 4.74 8.73 50 f0 3.5 5.31 9.90

From the above table it is obvious that the total body length ranges from 2 to 5.5 dm. and includes six O.5—dm. intervals with the mean of each interval equal to the sum of the body lengths, for the individual cases, divided by the number of cases falling within the interval. The corresponding average for the transverse diameter was then determined for each 0.5—dm. interval. The averages for the diameter were then proportioned so that about one—half of them would fall on one side of an imaginary line and one—half on the other side, as shown iii the following tabulation:

GIKOFP A GROUP B

Average body length (X) l Observed lnean tY) iAverage length (lX7),fl Observed mean (Y)

11 m. 7 mm. dm. mm. 2.35 ‘ 5.26 3.77 6.93 2.77 j 5.53 i 4.16 ‘ 7.35 3.29 l 6.40 1 4.74 8.75

l

32.93’ H

l l

5.31 9.90

Total 8.41 17.19 ‘ 17.98 . l

Averages for each group were summed and arranged ac— cording to the formula: Y=aX+bn. Y is the total ob— served averages in o11e of the groups, aX the sum of the total observed averages of length times a and Mt is the number of average points times I). If group A be arranged according to the form of the expression, it will then read: 17.19 2 8.4151 + 3b. Proceeding iii a similar manner with group B, the following expression is derived: 32.93 2: 17.9821 —l— 4b.

In order to solve for a and b, it is necessary to eliminate one or the other. The 19 constant is the more readily removed by finding the least common multiple for 3 a11d 4. This accom— plished, the two equations are then subtracted, the smaller from the larger, and the value of a determined.

17.19 :_— 8.41a + 3b 32.93 = 17.98a + 4b or a11d or 68.76 = 33.64a + 121; 98.79 = 53.94a + 12b

98.79 : 53.94a + 12b 68.76 = 33.648 + 12b

36.03 = 20.30.21 21 =_a9;g3 : 1.48 20.30

Knowing the value of a, it is then easy to determine b by substituting for a i11 one of the above equations.

17.19 =s.41(1.4s)+ 3b 3b : 17.19— 12.44, or 1) =4.75

3 b=1.58

Having obtained these constants, the numerical expression of the transverse diameter of the fossa is the following: Transverse diameter in mm. = 1.48 body length (dm.) -1- 1.58. Values computed by means of this formula are to be found i11 table 4.

ABSOLUTE GROWTH CHANGES The growth i11 weight of the hypophysis and its lobes when

plotted against the body—length measurements (crown-rump dimension used for the embryonic and early fetal life and 388 w. P. COVELL

crown—heel for the remainder of prenatal life) forms in each instance a shallow curve witl1 an upper concavity. The data represented by these curves may be represented approximately by means of the empirical formula: Y=aX". As will be shown later, the growth of the pars nervosa of the glaiid during the fetal life is the only data for weight of the hypophysis which could not be approximated by the above formula. The lineal determinations 011 the whole gland are approximated by the straight—line formula: Y=aX+b. The latter data include determinations 011 fetuses of 17) to 5.3 cm. in total body length.

The data dealing with the weight of the hypophysis in prenatal life have been separated into two parts and empirical formulae derived for the expression of growth in each instance. Since the embryonic a11d early fetal material was recorded in terms of the crown-rump measurement, certain difficulties were encountered in trying to approximate this period of growth with the same formula for the remaining‘ part of prenatal life. Embryonic (éliaiiges in growth are more rapid than those for the fetal period, hence a more accurate approximation of the growth changes in Volume were deduced from a separate treatment of these data.

1. Lizzcal (linzcnsio-12.9‘ of flu‘ _(/Jami’.

The growth of the Various diameters of the gland in fetuses 1‘zt11g'i1)e; from 15 to 55 cm. in total body length is represented in table 1 a11d figures 1, 2, and 3. The growtll of each of the three diameters, which represent the maximum dimension of the gland in the plane in wl1icl1 they were measured, may be approximately expressed by means of a rectilinear formula. Although the general character of growth is much the same for each, the amount of growth appears to Vary. They will thus be considered separately.

a. '1’rans*2rM'sc dianzdcr. The transverse diameter is the largest of the three dimensions and represents the maximum distance from one lateral side of the gland to the other. The growth of the transverse dimension for this part of prenatal life may be expressed by the formula: Transverse diaineter of the liypopliysis ((-1n.) : 0.01178 [total body length (cm.)] + 0.1985.

Values computed by this formula for 5—em. intervals of body length and compared with the observed averages for the same intervals show a11 average absolute deviation of 0.024 cm. from the latter. The average percentage deviation of the computed from the observed values is 3.89. According to the values obtained by means of the formula, the transverse diameter of a hypophysis from a fetus measuring 15 cm. in length is 0.375 cm. This increases to 0.493 cm. for a 25—cm. fetus, 0.611 cm. for one of 35 cm. and rises to 0.787 cm. in a 50-cm. fetus.

TABLE 1

0l).S’€)'t'€(l and calculated ralucs of the diamcI.‘ers of the hypophysis in fetuses rmzging in total body length from 15 to 55 cm.

M KAN ‘ 1{U\[]3 1.; 1; 2‘\q[‘1;I:‘]:1:E I I:\[)I;":‘l?;(I)(')R CRE::§I(;1::;I4:L OF QASES 1 DIA.\u-‘.'1‘1-:R ‘

Observed Calculated ()bserved Caleillated Observed Calculated cm. cm. cm om. rm. rm. cm. cm. 17.73 3 0.403 0.407 0.222 0.231 0.203 0.221 22.50 5 0.486 0.404 0.285 0.282 0.258 0.202 27.6.‘) 10 ()..");')3 (‘.524 0.330 0.337 0.339 0.307 32.74 13 0.610 0.584 0.390 0.302 0.406 0.350 37.46 12 0.630 0.63.‘) 0.446 0.443 0.390 0.390 42.67 8 0.675 0.701. 0.470 0.498 0.434 0.43.3 47.45 12 0.686 0.757 ‘ 0.526 0.550 0.386 0.476 52.62 13 0.822 0.818 0.307 0.605 0.492 0.519

It would thus appear from the above values that the transverse diameter of the gland increases about twofold between the stages of 15 and 55 cm. of body length (erowirheel).

b. Antc:v)p0sterior (lianzmmr. The anteroposterior diameter of the hypophysis is the second largest of the three diameters and represents the maximum dimension of the gland from the anterior to the posterior direction. Further, it is the only one of the three diameters which involves the pars nervosa as well as the anterior lobe.

JDHI0I6i0Z(Z4Z6t‘d}01’}{J6)6404Z444640.705Z54}0Un

mi—Tr-r‘u—r‘1'1—rr1-1—Tr

'/94 /6 /6 Z0 Z5 Z4 Z6 Z5 )0 J8 J4 J6 13 40 48 44 46 46 50 J? 54 525cm.

Fig. 1 Field graph, with the curve of the empirical formula, of the growth of the transverse diameter of the hypophysis in fetuses ranging from 15 to 55 cm. (er0wn<heel). Abseissae: total body length in eentimeters. Ordinates: transverse diameter of the hypophysis in centimeters. Individual cases are indicated by solid dots. Averages for 2.5-cm. intervals of body length indicated by circled dots. Curve drawn to the empirical formula:

Transverse diameter of the hypophysis (em.) 2 0.01178 [total body length ((:m.)] + 0.1985.

The approximate growth of the anteroposterior diameter may likewise be numerically expressed in terms of a straightline formula:

Anteroposterior diameter of the hypophysis (cm.) = 0.0107 [body length (cm.)] + 0.0408.

The average absolute departure of the computed from the observed means for 5-em. intervals of body length is 0.015 cm. The average percentage deviation of the same is approximately 3.4. The values obtained by means of the empirical formula give the anteroposterior diameter as 0.20 cm. in a fetus of 15 cm., 0.31 cm. for one of 25 cm. in length, and 0.41 cm. for one of 35 cm. in total body length. The anterior posterior diameter in a full-term fetus of 50 cm. is about 0.57 cm. This dimension of the gland increases somewhat more than the transverse diameter for the same intervals of prenatal body length. The number of times which this dimension increases in fetuses measuring from 15 cm. and up to 55 cm. is in the neighborhood of threefold.

(.’. Vertical diameter. The vertical diameter is the smallest of the three diameters of the gland and represents the maximum dimension from its inferior surface to the junction of the infundibular stalk with the main body of the hypophysis. Since the infundibular stalk was severed at the junction with

the body of the gland, none of it is included in the measurements.

Fig. 2 Field graph and curve illustrating the growth of the hypophysis in the anteroposterior diameter for fetuses ranging in total body length from 15 to 55 em. Abseissae: total body length in centimeters. Ordinates: anteroposterior diameter in centimeters. Individual cases indicated by solid dots. Averages for 2.5—cm. intervals of body length indicated by circled dots. Curve drawn to the formula:

Anteroposterior diameter of the hypophysis (cm.) = 0.0107 [body length (cm.)] + 0.0408.

Fig. 3 Field graph, with curve of the empirical formula, of the growth of the vertical diameter of the hypophysis in fetuses ranging in total body length from 15 to 55 cm. Abscissae: body length in centimeters. Ordinates: vertical diameter of the hypophysis in centimeters. Individual cases represented by solid dots. Averages for 2.5-em. intervals of total body length indicated by circled dots. Formula for the expression of the curve:

Vertical diameter of the hypophysis (em.) : 0.0085 [body length (cm.)] + 0.0705.

The growth of this dimension of the gland may be approximately expressed by the simple empirical formula:

Vertical diameter of the hypophysis (('1n.) 2 0.0085 [body length (cm.)] + 00.0705.

The mean values calculated by means of this formula show an average departure of 0.028 cm. from the observed means for the corresponding 5—cm. intervals of body length. The average deviation, in terms of per ee11t, is 7.74. VVhile this figure exceeds the average percentage deviations of the other two diameters, it is not too large to consider the formula a fair approximation of the rate of growth of the hypophysis in this diameter. The calculated vertical diameter of the gland in a ].3—em. fetus is 0.19 cm., for a fetus of 25 cm. it is 0.28 cm., for one of 35 em., in total body length, it is 0.37 cm. In a full-term fetus of 50 cm. in body measurement it is 0.49 cm.

The vertical diameter appears to increase in the neighl)01'hood of threefold from a fetus of 15—cm., erown—heel or total body length, to one of 0;) cm.

2. Total 'm'igl2f of the gland

a. EnzIn'ym1i(? a/ml early fetal life. The growth in weight of the hypophysis for part of prenatal life may be approximately expressed by the empirical formula:

\V(-ight of the hypophysis (mg.) 2 0.022 (crown-rump ((-111.)”~“"‘).

Table 2 is a comparison of the observed with the calculated data, while figure 4 is a shallow curve with the individual cases and average points plotted.

The mean values obtained by means of this formula, for 25—mm. intervals of crown-rump measurement, when compared with the observed values for the corresponding intervals, show an average relative departure of 17.2 per cent. The average absolute deviation from the observed average is 0.16 mg. The calculated weight of the gland for an embryo of 10 mm. is 0.03 mg., for one of 50 mm. in length it is 1.01 mg. The computed weight of the organ for a fetus of 100 mm. (crown-rump) is 5.28 mg.

It is obvious that the growth in weight of the gland for the early part of prenatal life is exceedingly rapid. From the above computed values the hypophysis may be said to increase nearly 200 times in weight in material measuring from 10 mm. to 100 mm. (crown-rump).

1). Fetal life (in f(>tuse3 [ranging from 15 to 55 ('m., fofal body length. The growth of the hypophysis in weight during the fetal period is illustrated in table 3 and figures 5 and 6. V\/‘hen the individual Weights of the glands are plotted against the cro\vn—heel measurements of the fetuses, a shallow concave curve is formed. This curve may be expressed in approximate numerical terms by means of the empirical formula:

VVeight of the hypophysis (mg.) = 3.834 (body length (dn1.)“’“).

TABLE 2

Observed and calculated values for the weight of the whole gland and its lobes in embzjw/(mic and early fetal life

_\n.~,AN V V \\'EIG 111' or THE WEIG}['l‘ or‘ THE \VElGH'l‘ or T}-IF. \\'El('iIl'I‘ 017' THE CROV\'N~ NL"‘”f“ HYPOPHYSIS PARS AN’I‘ERI(1R PARS INTERMEDIA PARS NERVOSA RCMP 01: ‘ LENGTH CASES Observed (‘nlculzited Obsei-ve(l (‘alt-ulated Observed Calciilated Observed Calculated mm. my. mg. mg. mg, mg. mg. mg. Wily. 11.0 1 0.0-1'1 0.028 0.032 0.030 . . . . .. 0.0005 0.001 0.0004 35.6 5 0.533 0.453 0.473 0.430 0.0169 0.0118 0.039 0.022 62.5 2. 2.094 1.725 1.800 1.542 0.0640 0.0532 0.170 0.144 87.6 3 3.653 3.838 33.866 3.313 0.1098 0.1313 0.410 0.441

The values calculated by this formula show an average

absolute deviation of 1.6 m0‘. from the corresponding observed averages for 5—cm. intervals of body length. The percentage deviation of the same is about 3. The range of the relative departures of the calculated from the observed values is +0.88 to + 6.8] per cent. The latter deviation falls Within the interval of the crown-heel range of 20 to 25 em. The relative deviation for the interval just preceding it is — 1.09 per cent, while the figure for the successive interval is + 0.88 per cent.

According to the above formula, the weight of the hypoph~ ysis is about 8.8 mg. in fetuses of 15 cm. (crown-heel), 25 mg. 394 W. P. COVELL

in 25-em. fetuses, 51 mg. i11 35-cm. fetuses, 86 mg. in 45—cm. fetuses, and approximately 107 mg. in a full-term fetus of 50 em. in total body length. It is thus obvious that the approximate increase in weight of the hypophysis in a fetus of 15 cm. to one of full term is roughly eleven— or twelvefold.

Figure 6 is a shallow concave curve which illustrates tl1e growth in weight of the gland during the fetal period in terms of fetal or lunar months, the fetal age being determined from the following formula developed by Seammon and Calkins ("23) :

T (age in fetal nio11tlI.<): 2.3 +/2.5L + L” 28 734

In the beginning of the fetal period the hypophysis weight is approximately 5 mg. This value is doubled between the fourth and the fifth months and increased fourfold by the end of the fifth fetal month. By the beginning of the seventh month, the computed weight has increased about tenfold. It is thus about 50 mg. iii a fetus of the seventh fetal month. During the ensuing three fetal months the hypophysis weight increases even more rapidly. By the tenth month (birth), it has increased about twe11ty- to twenty-twofold of the weight at the beginning of the fetal period. It is thus obvious that the gland increases in weight about tenfold between the third a11d seventh fetal months and an equal amount between the seventh month a11d birth.

Fig. -1 Field graph and curve of growth in weight of the hypophysis in embr_\'onic and early fetal life. Abscissae: ('l‘0Wl1-1‘1lll1p in millimeters. Ordinates: weight of the hypophysis in milligrams. Individual cases indicated by solid dots Averages for 25—mn1. intervals of (-1'own—rump intlieated by circled (lots. Curve drawn to the empirical formula:

VVeight of the hypophysis (mg.) : 0.022 (erown—ru1np (c111.)“"‘”).

Fig. 5 Field graph and curve of the growth of the hypophysis in weight in fetuses ranging from 13 to em. in total body length. Abseissae: crown-heel in centimeters. Ordinates: total weight of the hypophysis in milligrams. Individual cases indicated by solid dots. Averages for 2.5-eni. intervals of body length indicated by circled (lots. Curve drawn to the empirical formula:

\Veight of the hypophysis (111g.) 2 3.834 (body length (dm.)”“"’“).

5.5 1725. 5.0 4.5 4.0 15 10

Z5

Z0

/05 I00

JI4I6IdZ0t234£Oc‘dJ0J[}4J6}d404L‘44464d505c’545Ocm.

.5’. lVeig/It of the lobes of the gland

a. Emb1'y(mic aml early fetal life. Pars anterior. The gro\\'tl1 clianges i11 weight for the pars anterior during embryonic and early fetal life resemble very closely the type of changes whieli occur for the total gland weight of this time. This is 11ot unusual, since the pars anterior comprises relatively more of the hypophysis in the early periods of (level TABLE 3

()I;.wrz*ul mu! calculutw? values for the weiglzt of the whole gland and its parts in f(’t1l.s‘e.s' rangizzg in fatal botly lengtlz from 15 to 55 cm.

u 1-:,\); \\'r:n:n'r or win: \VI<]lGH'l‘ or THE WEIGHT or THE wt-:|<:n'r 01-‘ THE

L-R0“-N. N(.M“ER }[Y1’()l’HYSIS PARS .-\N'r1-;R1oR PARS IN'rER.\nmIA PARS NF.R\‘()S.\ HWTIA or CASES I‘ENG'T” (lhserved Cailculated Oliserved Calculated Ol>ser\'ed Calculated ()1-served (‘alculnted cm. mg. my. my. ‘in g. 'n'I_(/. m 1/. 'm 1/. W1 g .

1.7.73 3 12.636 12.518 10.033 10.498 11.314 0.387 I 1.409 1.782 21.30 4 18.820 20.102 16.20.’; 16.613 0.566 0.561 10.49 .2 277 27.41 11 30.518 30.787 26.110 23.101 0.843 0.781 I 3.564 2.761 33.74 13 44.861 44.436 41.720 35i.8‘_’.6 1.084 1.039 5 5.1322 5.239 37.46 12 55.483 58.608 47.130 46.899 1.254 1.291 I 7.076 7.634 42.61 12 81.441 76.603 68.310 60.684 . 1.517 1.588 11.616 11.713 47.43 12 04.300 071.638 74.440 75.272 . 1.920 1.887 ‘ 14.680 16.960 .':.‘2.G‘_’ 17> 117.106 118.432 531.840 02.563 1.212 2.229 23.058 1 ‘35.591

opment than later. Table 2 and figure 7 illustrate the growth of this part. It may be expressed numerically by means of the empirical formula:

Weight of the pars anterior (mg.) 2 0.0242 (crown-rump (em.)“‘").

The average (liffereiice between the observed average Values a11d those calculated by means of the formula for 25—mm. intervals of erown—heel measurement is 0.203 mg.

Fig. (3 Curve illustrating the weight of the hypophysis in terms of fetal months. AlJS('lSSI1L‘: age in fetal months. Ordinates: weight of the hypopliysis in milligrams.

Fig. 7 Field graph, with curve of empirit-al formula, of the growth in weight of the pars anterior in embryonic and early fetal life. Ahseissae: crown»rump in millimeters. Ordinates: weight of the pars anterior in milligrams. 'In(li\‘i(lual vases indicaterl by solid dots. (llI'('l(’(l dots indicate average points for 2:3-mm. i11t(-rvals of crown—rump. Curve drawn to the formula:

Weight of the pars anterior (mg.) = 0.01342 (crown-rump ((':m.)’-2°’).

110

100

80

70

50

30

O ! I I I 1 1 s 3 4 5 O 7 6 9 10 Fetal months

.0 I0 20 J0 40 50 60 70 60 90 /00mm.

The largest of the absolute deviations of the calculated from the observed values falls within the last two intervals of 50 to 100 mm. The relative differences are the largest in these intervals. The average percentage deviation for the four intervals of the body length is 12.1.

The values calculated from the above formula are as follows: For an embryo of 10 mm. the approximate weight of the anterior lobe is 0.024 mg., for one of 50 mm. it is 0.929 mg., and about 4.09 mg. for a fetus of 100 mm. (cro\vn—rump). The pars anterior of the hypophysis increases in weight from the period under consideration about 200-fold. The growth i11 weight of the whole gland and the pars anterior are ver_v nearl_v identical as regards the number of times which their weiglit is doubled for the part of prenatal life.

Pars intermedia. Figure 8 illustrates, by means of a sl1al— low curve, the changes which occur in the weight of the inter— mediate lobe. The growth of the pars intermedia for the embryonic a11d early fetal life may be approximately expressed by means of the empirical formula:

\\'eight of the pars intermedia (1ng.)=0.000393 (erown—run1p ((=111.)‘-’-‘““).

The calculated weight of this portion of the gland for an embryo of 10 mm. (crown-rump) is approximately 0.0004 mg.: in a11 embryo of 50 mm. it has increased to about 0.029 mg‘.; tinally, in a fetus of about 100 mm. (crown—rump) it is approximately 0.187 mg.

Since the volumetric estimation of the pars intermedia is (lifficult to determine in an embryo of 11 mm., only the calculated weight is given for the first interval. The other three intervals of crown—rump up to 100 mm. show a relatively high departure of the observed from the calculated values. These are probably of very little significaiice, since the pars intermedia is small and obviously the most difficult. of the lobes to determine volumetrically. The computed values are only a rough approximation of the growth changes in weight for this part of the gland in early intra—uterine life.

Pars nervosa. Figure 9 and table 2 illustrate the growth of the pars nervosa in embryonic and early fetal life. It differs from the type of growth of the other two lobes by the fact that it appears later in embryonic life and increases at a comparatively slow rate up to a certain point, from which time on it increases rapidly. The empirical formula derived for the approximate expression of its growth is:

Weight of the pars nervosa (mg.) =0.000335 ((‘1'0w11-1'1lmp (ozn.)“4“"’).

The average relative deviation of the observed from the computed values for 25—mm. intervals of crown—rump is about 22 per cent. The average absolute deviation for the same is about 0.02;’) mg. The computed weight of this part of the hypophysis iii an embryo of 10 mm. is 0.0003 mg.; in an embryo of about 25 mm. this weight has increased to 0.007 mg.; in one of 50 mm. the approximate weight. is 0.068 mg., and finally in a specimen of 100 mm., crown-rump, it is about 0.68 mg. It is thus obvious that the weight increases about 100fold from the stages of a 25-mm. embryo to a fetus of 100 mm.

1). Fetal life (in fetuses rai/aging from 15 to 55 cm., total body Zen;/tie). Pars anterior. The changes in weight of the pars anterior are shown in table 3 and illustrated in figure 10. This portion of the gland appears to grow in a manner similar to that of the total gland weight. Such a similarity in the two curves is expected, since the pars anterior comprises the larger portion of the total gland volume. The empirical formula for the approximate expression of the shallow concave curve is as follows:

\‘\‘'eight of the pars anterior (mg.) = 3.338 (body length (dm.)"-'-""‘).

VVhen the calculated values are compared with the observed averages for 5—cm. intervals of body length, the average (leparture of the former from the latter is roughly 2.1 mg. The average relative deviation of the same is 4.75 per cent. The range of the relative deviations of the calculated from the observed values is -4- 0.78 to ~—14.14 per cent. The larger deviation is for the crow11—heel interval of 30 to 35 cm. It is 400 W. P. COVELL

negative and is preceded and also followed by negative departures of much smaller significance. There is also a negative deviation of 11.17 per cent for the body-length interval of 40 to 4.5 cm. This, however, is preceded by a negative deviation of 0.53 per cent, a11d a positive deviation of 1.11 per cent for the succeeding interval. It is thus apparent that the differences of the calculated from the observed values are in fair agreement.

The weight of the pars anterior as computed for a fetus of 15 cm. (crown-heel) is about 7.6 mg., for one of 25 cm. it is 21.1 mg., for a 45—cm. fetus the weight of the pars anterior is 68.4 mg., and for a full—term fetus of 50 cm. it is approximately 83.4 mg. It is obvious that the weight of the pars anterior increases about elevenfold from a fetus of 15 cm. to one of full term.

Pars intermedia. The growth of the pars intermedia is illustrated in figure 11 and table 3. When the weights of this portion of the gland are plotted against the body length (crown-heel) of the fetus, a shallow curve is formed which closely resembles that described for total gland weight and weight of the pars anterior. It may be approximated, numerically by the following empirical formula:

Weight of the pars intermedia (mg.) : 0.1544 (body length (dni.)"“°3).

Values obtained by means of this formula show an average absolute departure of 0.043 mg. from the observed averages

Fig. 8 Field graph and curve of the growth in weight of the pars intermedia in material ranging from 10 to 100 mm., (-.rown—rump. Abseissae: erown—rump in millimeters. Ordinates: weight of the pars intermedia in milligrams. Individual eases indicated by solid dots. Cirt-led (lots indicate averages for 25-min. intervals of crown-rump. Formula for the expression of growth in weight:

\Veight of the pars intermedia (mg.) =0.000393 (crown-rump (cm.)““").

Fig. 9 Field graph and curve illustrating the growth in weight of the pars nervosa in material ranging from 10 to 100 millimeters, crown—rump. Abseissae: (-rown-rump in millimeters. Ordinates: weight of the pars nervosa in milligrams. lndi\'i<lual cases in solid dots. Averages for 25—mm. intervals of erown-rump indicated by circled dots. Curve drawn to the formula:

Weight of the pars nervosa (mg.) =0.00().-‘$35 (crown-rump ((*111.)““").

0]0ZOJ0405000708090}00mm.

3 1.‘ 0 /0 Z0 }0 40 50 D0 70 50 90 ]00I7}I‘n

401 402 w. P. COVELL

for the corresponding C)—cm. intervals of total body length. The average relative deviation of the same is 6.71 per cent. The largest individual percentage deviation of the calculated from the observed values falls within the interval of total body length with a range of 15 to 20 cm. It is + 23.25 per cent and is followed by a departure of ——8.83 per cent. The six remaining relative deviations are all below 7.5 per cent. Three of these are positive and three are negative. The smallest departures for the relative differences are for the newborn material.

The computed weight of the pars intermedia is approximately 029 mg. in a 15-cm. fetus, 0.67 mg. iii a 25—cm. fetus, 1.73 mg. in a 45—cm. fetus, and 2.05 mg. for a full—term fetus (50 cm.).

Pars nervosa. The growth in weight of the pars nervosa of the hypophysis is shown in table 3 and illustrated in figure 12. VVhen the weight of this part of the gland is plotted against the body length of the fetus, a shallow concave curve is formed which may be approximated by the formula:

\Veight of the pars nervosa (mg.) : 0.384 (e 0.798 body length (dm-l).

This curve shows a gradual increase in weight of the pars nervosa up until 35 cm., and a more rapid rise from then 011. The values computed by means of this formula show an average absolute deviation of 0.837 mg. from the corresponding observed averages for ;')—em. intervals of body length.

Fig. 10 Field graph and curve illustrating the growth in weight of the pars anterior in fetuses ranging from 15 to 55 cm., erown—hcel. Abscissae: crown~hee.l in centimeters. Ordinates: weight of the pars anterior in milligrams. Individual observations indicated by solid dots. Circled dots indicate averages for 2.5-(-in. intervals of total body length. Curve drawn to the formula:

Weight of the pars anterior (mg) = 3.338 (body length (dm.)““‘).

Fig. 11 Field graph and curve of the growth in weight of the pars intermedia in fetuses ranging from 15 to 55 cm. in total body length. Abscissac: body length in centimeters. Ordinates: weight of the pars intermedia in milligrams. Individual observations indicated by solid dots. Cireled dots indicate averages for 2.5-cm. intervals of body length. Curve drawn to the empirical formula:

Weight of the pars intermedia (mg.) = 0.1544 (body length (dm.)‘-"""). 8 7 6

.5

.4 ) Z I

/4/o to 202224 2o 2oJo12)4J¢x4a42444am 5052 54,5érm

The average percentage deviation of the calculated from the observed values is 10.16 per cent. The range of the relative deviations is from 0.88 to 22.53 per cent. The largest relative difference falls within the body—length interval of 25 to 30 cm. It is, however, preceded by a positive deviation of 11.13 per cent and followed by a positive deviation of 3.26 per cent. The computed values appear to be closest in their agreement with the observed values between the intervals of 30 to 45 cm. (crown—heel ).

According to the above formula, the weight of the pars nervosa in a 15—cm. fetus is 1.26 mg., in one of 25 cm. it is about 2.82 mg., in a 45—em. fetus it is 13.87 mg., and 20.7 mg. in a full-term fetus of 50 em. in total body length. It is thus obvious that the posterior lobe increases about sixteenfold from a 15-cm. fetus to one of full term.

4. Lineal dime/nsio/ns of the hypophyseal fossa

The growth of the hypophyseal fossa in the transverse, anteroposterior, and vertical diameters is illustrated in table 4 and figures 13, 14, and 15. The hypophyseal fossa is usually larger transversely than in the other diameters. The anteroposterior diameter is second i11 size, while the vertical diam Fig. 12 Field graph and curve of the growth in weight of the pars nervosa in the fetal period. Abseissae: body length in centimeters. Ordinates: weight of the pars nervosa in milligrams. Individual eases represented by solid dots. Cireled dots indicate averages for 2.5-em. intervals of body length. Curve drawn to the formula:

Weight of the pars anterior (mg.) = 0.0242 (crowlfi-rump (cin.)2-267).

Fig. 13 Field graph and curve of the growth of the transverse diameter of the hypophyseal fossa in fetuses ranging from 20 to 55 cm. in total body length. Abseissae: body length in centimeters. Individual cases indicated by solid dots. Ordinatesz transverse diameter of the fossa in centimeters. Averages for 5-em. intervals of body length indicated by circled dots. Curve drawn to the formula:

Transverse diameter of the hypophyseal fossa (cm.) :1.43 [body length (dn1.)] + 1.73.

Fig. 14 Field graph and curve of the anteroposterior diameter of the hypophyseal fossa in fetuses ranging from 20 to 55 cm. in total body length. Abscissae: body length in centimeters. Ordinates: diameter of the fossa i11 eenti« meters. Individual cases indicated by solid dots. Cireled dots indicate averages for 5-cm. intervals of body length. Curve drawn to the formula:

Anteroposterior diameter ((-m.) = 0.592 body length (d1n.) + 2.41. .70 .05 .00 .55 .50 .45 .40

.35 .5

(7 6 4 5 vs. 014/1: /a i|0Z;2-l1_Z|éz“4l5f§(1_3l£-31-¢.4+0fl!*<1 4a 50 52 54 Jacm I./5 C77). I./U /.0} /.00 .95 .90 .05 .50 .7} .70 .05 .60 .55 .50

‘45

‘4%ozaz4:ozax2)zJ4)o1a4o4z444o4a5o25450:».

. 75 cm.

0&0 Z6 Z4 Z6 Z6 )0 J3 54- J6 36 40 42 44 46 46 f0 55 54 56cm. 406 w. P. COVELL

eter is the least of three. The transverse diameter represents the maximum distance between the lateral extremities of the fossa. The anteroposterior diameter is the distance between the anterior surface of the dorsum sellae and the posterior border of the tuberculum sellae. The vertical dia 1.eter is the distance from an imaginary midpoint on the anterior posterior diameter to the floor of the fossa. The growth of the three diameters may be approximated by means of straight-line formulae. Since there are certain peculiarities individual to each, they will be considered separately.

TABLE 4

()I)serve(l and calculated values of the diameters of the hypophg/seal fvssa in fetuses 1'a¢1ging in. total ‘I)ody-l€7:gth from 20 to 5.5

'l‘RANS\’ERSE ANTI-2R0-Pos'rERIOR vi-:m‘IcAI. "BAN xunmm I)IAME’I‘ER mA.\n~:'ri:R 1>IA.\n«:'1*nR ”“‘).:“;1:’(;I,I{,I“‘IEI‘ OF CASES Observed Calculated Observed (‘aleulated Observed Calculated cm. rem. om. rm. cm. cm. cm.

23.46 5 0.526 0.500 0.380 0.380 0.200 0.200 27.73 3 0.533 0.563 0.373 0.405 0.187 } 0.214 32.89 10 0.640 0.639 0.467 0.437 0.258 1 0.232 37.67 8 0.093 0.711 0.457 0.464 0.235 0.248 41.68 5 0.735 0.769 0.476 0.487 0.248 0.262 47.35 12 0.875 0.853 0.486 0.521 0.280 0.281 53.08 7 0.990 0.938 0.622 0.55.’) 0.341 0.301

a. Transverse diameter. The growth of the transverse diameter in fetuses ranging from 20 to 55 em. in total body

length may be approximately expressed by the empirical formula:

Transverse diameter (mm.) = 1.43 [body length ((lm.)] + 1.73.

The values obtained by means of the formula and compared with the observed values for the corresponding 5—cm. intervals of body length show an average absolute departure from the latter of 0.024 cm. The average percentage deviation of the same is 3.25.

1). Amteropostelrior‘ diameter. The growth in the a11tero—

posterior diameter may be expressed by the formula: Anteroposterior diameter (mm.) -—-0.592 [body length (dm.)] + 2.41.

The mean percentage deviation of the calculated from the observed values is 5.32 and the absolute deviation is 0.026 cm.

0. Vertical diameter. The changes in growth of the depth of the hypophyseal fossa may be approximated by means ofi a straight-line formula:

Vertical diameter (mm.) =0.343 (body length (dm.)) + 1.191.

TABLE 5

The 7'elat2't'e volume of the lobes of the hypophysis for material between 11 and J00 mm. (crown-rump)

RELATIVE VOLUME RELATIVE VOLUME RELATIVE VOLUME CASE NO. CRO\\'N-HUMP OF PARS OF PARS OF PARS ANTERIOR IN'l‘l<‘.RMEDIA NERVOSA Per cent 1’I'r (rent 98.35 . . .. 1.65 91.60 2.59 5.81 89.03 3.37 7.60 86.45 4.41 9.14 88.46 3.03 8.51 90.28 3.19 6.53 88.26 3.08 8.66 87.17 3.20 9.63 84.24 3.96 11.80 86.05 2.11 11.84

The average mean departure of the calculated values for

')—cm. intervals of total body length from the observed values for the same measurements of body length is about 0.017 cm. The absolute mean deviation for the above is 6.82 per cent.

The range of the relative differencesis from 0 to 14.44 per cent.

RELATIVE GROWTH CHANGES

The relative volumes of the lobes of the hypophysis are shown in tables 5 and 6 and figure 16. The relative volume of each lobe appears to change as the fetus approaches the 408

W. P. COVELL

TABLE 6

Relative volumes of the lobes of the hypophg/sis in fetuses ranging from about 90 to 55 cm. in total body length (twenty-nine cases)

CASE NO.

FP5 FP-1 FP7

M01111

Case 3 2~1——165 FF 2 1727 1732

M02111

24-25 FP 1 24-796 1744

M ea 11

24-24 23-849 1737

M ezm

25-17 1766 24-559 22-—323

Mean

23-409 24-795 23-224

Mean

3531 1746 1765 1735 23-840 24-251 24~60

Mean

1 1 1

TOTAL BODY

1RELATIVE VOLUME ‘ 01‘ THE PARS

OF THE PARS

msnmxvm VOLUME 1RELA'I‘IVE voLL'.\1n 01‘ THE PARS 1

LENGTH 1 ANTERIOR INTERMEDIA 1 NERVOSA 1 1 cm. 1 Prr vent PP?’ vent Per cm!‘ 21.5 85.46 3.02 12.42 22.2 1 87.51 2.90 1 9.59 25.4 1 86.25 3.09 10.66 1 86.11 1 3.00 1 10.89 27.0 1 85.50 1 2.74 1 11.76 28.0 1 87.50 ‘ 2.46 1 10.04 29.2 1 85.91 2.33 1 11.76 29.5 1 81.15 1 3.35 1 15.50 30.0 1 86.91 1 2.63 1 10 46 __ 1.“- 1 .1- __ 1 85.40 1 2.70 1 11.90 1 1 31.0 1 85.61 2.77 1 11.62 34.3 1 87.32 1.77 ‘1 10.91 35.0 1 85.89 1 2.09 1 12.02 35.2 1 85.70 1 2.30 12.00 1 86.13 1 2.23 1 11.64 1 38.0 83.60 2.15 1 14.25 39.0 85.80 1 1.70 1 12.50 40.0 84.94 1 2.95 1 12.11 84.78 1 2.27 12.93 41.3 82.57 1.98 15.45 42.0 86.06 1.76 1 12.18 42.5 83.21 2.29 14.50 45.0 84.59 1.45 1 13.96 1 83.86 1.86 1 14.38 1 46.0 77.53 1.66 1 20.81 45.5 78.33 1 2.82 18.85 49.0 80.00 1 - 1.70 1 18.30 1 78.62 2.06 1 19.32 50.7 77.82 2.65 19.53 51.5 70.05 1 2.14 1 27.81 51.5 78.71 ‘ 1.82 1 19.47 51.0 78.78 1.22 1 20.00 54.0 82.26 1.54 1 16.20 54.5 84.13 1 1.67 14.20 55.0 77.22 2.22 20.56 78.42 1.89 1 19.69

tenth lunar month. The pars anterior comprises relatively more of the hypophysis in the embryonic and early fetal stages than it does later in prenatal life. The pars intermedia

5 /5 [5 .55 45 55 cm.

1%)": /Yen/osa Ear: /n/e/‘media Ram/Fnferlbr

.45 .40 . 35 .50 .85 . E0

./5

JOZO Z3 Z4 Z6 [:3 J0 J2 J4 J6 56 40 4E 44 46 40 50 52 54 56cm

Fig. 15 Field graph and curve of the vertical diameter of the hypophyseal fossa in fetuses ranging from 20 to 55 cm. in total body length. Abseissae: total body length in centimeters. Ordinates: vertical diameter of the fossa in centimeters. Individual eases indicated by solid dots. Circ-led dots indicate averages for 5~c1n. intervals of body length. Curve drawn to the empirical formula:

Vertical diameter of the fossa (em.) = 0.343 body length (dm.) + 1.91. Fig. 16 A histogram representing the changes in the relative volumes of the

three lobes of the hypophysis. The base line is marked off into 10~em. intervals of body length. The total gland volume for each interval is 100 per cent. 410 w. P. covELL

likewise comprises relatively more of the gland volume for the early part of intrauterine life. The pars nervosa apparently makes up less of the gland volume early in its fetal development than it does later.

Figure 16 illustrates the relative volumes of each of the lobes for 10—cm. intervals of body length from 5 to 55 cm. In fetuses of 5 to 15 em. (crown-heel) the anterior lobe comprises about 87.7 per cent of t.he total gland volume, the remainder of the volume is 3.16 per cent pars intermedia and 9.14 per cent pars nervosa. The relative volume of each part of the gland in fetuses of 15 to 25 cm. total body length is slightl_v changed. I11 this interval the pars anterior is 86.21 per cent, the pars intermedia is 2.78 per cent, and the pars nervosa is 11.01 per cent. From 25 to 35 cm. (crown—heel) the anterior lobe forms 85.78 per cent, the pars intermedia 2.58 per cent, and the posterior lobe (pars nervosa) about 11.64 per cent. In fetuses of 35 to 45 cm. in total body length the anterior lobe may be said to comprise about 84.56 per cent of the total gland volume; of the remaining 15.44 per cent, 2.07 per cent is pars intermedia and 13.37 per cent is pars nervosa. The most noticeable change in relative volumes appears to occur in the latter part of the fetal period. For the interval of 45 to 55 cm. the anterior lobe comprises about 78.62 per cent, the pars intermedia about 1.91 per cent, and the pars nervosa 19.47 per cent.

Table 5 gives the relative volumes of the lobes of the gland in embryonic and early fetal material. Table 6 gives the observed relative volumes and their averages for 5-cm. intervals of total body length. This is the arrangement of the observed relative values used for determining the approximate weight of the lobes of the hypophysis for the fetal series. VVhile these percentage values are only approximations, it is nevertheless evident that the three different lobes do not maintain the same rate of growth throughout the embryonic and fetal periods.

Relative litnlcreagse in the growth of the hypophysis, its lobes rmd the hiypophyseal fossa

The relative increase which occurs iii the hypophysis during the embryonic and early fetal life will be considered first. The amount of relative increase for this part of prenatal life is given in table 7 and figures 17 and 18. The weights of the gland and also of each of the three lobes are considered as being equivalent to 100 per cent in a fetus of 100 mm. (crown— rump). These data have been computed separately, because the early growth changes are different from the later.

TABLE 7

Weigltt of the hypophg/si.s' and its lobes -in (fmbryonic and early fetal lift! ('(lI('lI— lated in percentages of them‘ weights in CL fetus of 100 mm. (crowmrmnp)

CR0“.N,Rmu, W1-:1(;.H'r 01:‘ 'rH1~; \\'EIGll’l‘ or THE \\'EIGH'I‘ on THE \\'I~:lG}{'1‘ OF THE GLAND PARS AN'I‘l-‘.RI()R PARS INTERMEDIA PARS NEKVOSA mm. Per cent Per cent 10 0.37 0.10 30 3.93 1.90 50 ; 15.60 10.10 70 , 38.46 30.60 00 l 75.32 70.42

100 100.00 100.00

The total weight of the gland increases rather gradually to about 50 mm. (crown-rump), after which time it appears to rise more rapidly. The volume of the gland in an embryo of 50 mm. is roughly about one—fifth of the volume of the gland in a fetus of 100 mm. (crown—ruInp).

The pars anterior shows a relative increase very much similar to that for total gland weight. The curve of growth is more concave for 10 to 50 mm., after which time it rises rapidly to 100 mm. Here, again, the volume in a :30-mm. embryo is approximately one—fifth of the total weight in a fetus of 100 mm. (crown—rump). A

The pars intermedia apparently undergoes a similar rate of growth in these early stages. In an embryo of 50 mm. it represents about 15 per cent of the volume which it finally attains in a fetus of 100 mm.

700

90

60

70

(70

50

40

JO

[0

0 o :0 J0 40 50 so 70 60 90 /00mm.

—- /‘bra /ntermedia —— Rzra /Inferior

o /0 80 J0 40 I0 00 70 00 90 100mm.

Fig. 17 Curve illustrating the growth in weight of the hypophysis in the enibryonic and early fetal periods, computed in percentage values of the weight in 21 fetus of 100 mm., crown—rump. Abseissae: er0wn~rump in millimeters. Ordinates: per cents of values in a fetus of 100 millimeters, crown-rump.

Fig. 18 Curves illustrating the growth in weight of the lobes of the liypoph» ysis, in cnibryonic and early fetal material, computed in terms of the value in a fetus of 100 millimeters, cr0wn—rump. Abscissae: cr0wn—rump ‘m millimeters. Ordinatos: per eents of the value in a fetus of 100 millimeters, crown-rump.

The pars nervosa undergoes a much slower rate of growth in the earliest stages, but rises rapidly from 70 to 100 mm. In figure 18 it is obvious that the volume of the posterior lobe in an embryo of 50 mm. is only about 10 per cent of the volume of that part of the gland in a. 100—mm. fetus.

Changes in relative increase dmmg fetal life

The weights of the hypophysis and its lobes calculated in terms of per cent of their weight at birth are shown in table 8 and figures 19 and 20.

TABLE 8

Weight of the hypnphysis and its lobes calculated in percentages of their weights at birth (50.2 cm., total body length)

VVEIGHT OF THE 1 ‘\\'EIGH'l‘ OF THE PARS ANTERIOR PARS NERVO SA

TOTAL BODY LENGTH

WEIG KT OF THE HYPOPHYSIS

l 4

l l cm. 1 Per cent t Pm‘ renf Per cent 15 t 8.23 8.91 .| 6.09 25 l 23.69 22.61 I 13.62 35 4 47.44 48.62 g 30.29 45 l 77.69 80.27 ] 67.00 50.2 ‘ 100.00 100.00 3 100.00

I

The total gland Weight in a fetus measuring 15 cm. (crownheel) represents about one-twelfth of the Weight of the gland at birth. In a 25—cm. fetus the gland volume is approximately one—fourth of the weight which it attains by the time of birth. The gland of a 35-cm; fetus may be said to comprise about one-half of the hypophysis weight of a fetus of 50 cm. (crownheel). From the above facts it is obvious that the most rapid increase in relative volume occurs in fetuses ranging in total body length from 35 to 50 cm.

The pars anterior and pars intermedia are quite similar to the total gland weight in the amount and distribution of the relative increase. This statement is especially true of the pars anterior, which comprises by far the bulk of the gland. In a fetus of 15 cm. (total body length) the pars a11

/00

90

70

50

40 1

JO

[0

I9 /0 /5 20 :5 J0 )5 4o 45 50 55cm.

4

—- Pars /rflz:/77edia I " "‘ Pars; /‘in terio/‘

"'-' Pans /‘/pr vosa _j_§___ I i

/0 If Z0 (5 I0 17 /I0 /7 5 50 5%/v».

Pig’. 1!! (‘urw illustrating" the }.I:mw‘rl1 in wt-iglxf of the h§'1m]»l1.\'..s'i.s' in f<-tum-s r;u:;_{i11;;' frmn 1.’: to 37: rm. in total l>ml}' lmlgtll (‘(lHl])11Tl*[l in T(‘I'l1)S of H10 \':11u«~

11 lrirth. AI)S(‘i.\‘S2((‘2 lm(l_\' 14-ngth in m-I1tiI1wh‘1‘,s*. ()1'di11at<*.\': In-1' cmlfs of flu» Vuluv :11 luirth.

Fig". 21) (‘111'\'vs ilIush‘:lting' flu‘ g'1'm\"(l1 in weight «If 1111- lulws of the }1_\'[mph_\'.\‘i.< c-mnpuh-(1 in tor111>' of Hwir \':\Iuvs at birth. A])sriss.‘l1‘: <-1'm\'n—h('vl in 1-mlfivlwh-1's ()1-<lin:m-,<: pm‘ ('(‘1H‘S of tlw \':1I\u- of thu \\'('i;_rM at birth.

terior represents approximately one—twelfth of the Volume of the anterior lobe of a 50—cm. fetus, whereas the pars inter— media in a 15—em. fetus is about one—seventh of the Volume of the pars intermedia of a newborn. The latter estimate is slightly more than the relative Volume determined in per cent‘ of the gland weight and weight of the anterior lobe for the newborn.

The pars nervosa appears to grow differently from either of the other two parts or the total gland weight. The Weight of the pa.rs nervosa at birth is approximately sixteen times g1‘eatei' than the weight of this portion of the gland iii a fetus

TABLE 9

Lincal (Iimem-ions of the Ii_2/poplzg/.s-i.s~ computed in ymrcentages of their values at birth (.50.? cm., iotal body len_(/th)

H ,_ V _ 'l‘RANS\'ERSl<2 .\N'ri:Ro-rosT1—:i:Iok \'i:Ic'rIC.\L

'0'” BM" I'EM'”I DIAMF/r1-Ir. 1)[.\METER DIA.\IE'J‘1~1R cm. Pm‘ wen! Per cent P13!‘ We'll’, 1;‘) 47.58 34.89 39.84 23 62.47 53.37 56.94 33 77.35 71.83 74.04 43 9.‘3.2»l 90.33 91.13 30.2 ](l0.(N) l0l7.()0 100.00

of 15 em. (crown-heel). The most marked increase for this lobe begins to occur at 35 cm., erown—heel length, and by the time of birth it has increased nearly threefold in Volume.

H«'I(Ifirw z'1zm'('a.w' in lineal rlinwizsirnm

Table SD gives the lineal dimensions of the l1_Vpopl1ysis eom— puted in percentages of their size at birth. The anteropos— terior and Vertical diameters are approximatelv one—third as large as the same diameters of the l1_\'popli_\'sis of the ilexvborn. The trans\'erse diameter of the gland in a 25«0m. fetus repre— sents about two-tliirds or less of the same lineal dimension of the liypopliysis of a newborn. The anteroposterior and \'e1'tieal diameters for the same ag‘e are slightly more than one—half of the two diameters of the full—term fetus. The

transverse diameter of a fetus measuring 35 em., in total body length, is about three—fourths of the same diameter in the newborn. The anteroposterior and vertical diameters closely approximate the same relative values as the transverse diameter of a 35-cm. fetus. In a fetus of 45 cm. (crown—heel)

the diameters of the gland are about one—tenth less than the same diameters for a full—term fetus.

-- Hvpoptwysu unfit ———— Para newoaa weigh! Total body might -—--— Eyeball volume —- — Optic new volume ~— —- Cerebrum volume -—-—~ Cxmbcllumvolumc —— -- l‘1ldbf5ll’1VDl|-NT‘-C —- - ‘Pon: and mcdulh wlurm

i - 5pmal cord volume

Fig. 21 Curves illustrating the fetal growth of the total body weight, the volumes of the various parts of the brain, the spinal cord, optic apparatus, and the weights of the hypophysis and pars nervosa. The values have been reduced to a common scale by dividing the absolute values for 5—em. intervals of body length by the weight or volume at birth. Abseissae: total body length in centimeters. Ordinates: per cent of the value at birth.

I1’('lafi1>(% 2"I2(:r(?a3(: in the livzcal (Iim(371.3i012.s of the hypoplzyseal fossa

The relative increase of the various diameters of the hypophyseal fossa computed in terms of per cent of their size at birth are shown in table 10.

A glance at the three columns of figures representing the percentage values of each diameter shows that in a fetus GROWTH or HUMAN PRENATAL HYPOPHYSIS 417

of 20 cm. (crown—heel) the various diameters are from onehalf to two—thirds of the size which they attain in a full—term fetus. The transverse diameter increases at the rate of about 8 per cent for each 5—cm. interval of body length from 20 to 50 cm. It is thus about three-fourths of the size in a 35-cm. fetus of what it is in a full-term fetus.

The anteroposterior diameter, the second largest of the three diameters, represents about two—thirds in a 20-cm. fetus

TABLE 10

Lincal dimensions of the hypophyseal fossa computed in percentages of their size at birth (50.2 cm., total body length)

TRANSVERSE DIAMETER

VERTICAL DIAMETER.

ANTERO-POSTERIOR

TOTAL BODY LENGTH DIAMETER

I

I

I cm. PM cent W7 Per cent Per cent 20 51.52 66.73 64.50 25 59.48 72.30 70.38 30 67.56 35 75.53 E 83.27 82.13 40 83.61 I 88.85 87.97 45 91.58 94.24 93.81

N 9 l 77.69 76.29 t

100.00 50.2 100.00 100.00

of the same diameter of the fossa in a full-term fetus. It increases at the rate of about 4 to 6 per cent for each 5—cm. interval of body length from 20 to 50 cm. In a fetus of 35 cm. the diameter is a little more than four—fifths of that in a 50—cm. fetus.

The vertical diameter of the fossa is the least of the three diameters, but shows a similar increase in relative size to that of the anteroposterior diameter. In a fetus of 20 cm. it is slightly less than two—thirds of its approximate size at birth. It also increases at the rate of about 4 to 6 per cent for each 5—cm. interval of body length.

,1 mmpa,ri.swn of the fetal growth, of H/(1 Izgz/p0pl2y.s*i.s' with that of ()HI(’I‘ organs‘ and total body 1r("iK(/In‘

It has been shown i11 figures 4, 5, and T to 12 (inelu_si\'e) that the fetal g.>;rowtl1 in wei;:;lit of tlie hypophysis and its lobes when plotted against the total body length follow tl1e course of a shallow concave curve. It is obvious that the partes anterior and intermedia approximate more closely the

eneral type of growth of the total gland weigllt than does the pars nervosa. The latter presents a greater eoneayity to its curve.

Figiire 21 shows the percentage growth of the liypopllysis weigllt a11d the weight of the pars neryosa which are plotted on the same graph with Volumes of fetal brain parts, as determined by Dunn (’21), optic apparatus (Seammon and Armstrong, ’25) and total body weiglit (Seammon a11d (‘alkius, ’23). lt is evident that the hypophysis follows the general type of curve characteristic of the fetal growth in weight of the whole body as well as the volume of its parts.

The clianges in the growth of the gland as a whole approximate the growth of the Volumes of the eyeball, midbrain, and spi11al cord more closely than the other gzrowth euryes. The most outstanding <lift'ere11ee between the curve for growth of the hypopliysis and these curves is the age at which it l)egi1is to show the most. rapid increase. (It is somewhat earlier, being‘ apparent at about the body—leng'th measurement of 25 em., whereas the curves for eyeball volume, brain Volume, et(‘., show a rapid increase from 30 cm. oil.

The pars nervosa does not show the rapid increase u11til about 35 cm. It approximates in the type of growth the enrves for optic nerve Volume, eerebrum volume, and total body weiglit. It resembles the type of growth of the optie—nerVe volume in earlier fetal stages up to about 25 em.; from this time on it follows more closely the growth curves of body weigrllt and eerebrum volume.

A (-mnparismz of HM r«»lati‘z.'e rolmmns of the 101203 of Her: Izumtm piwzafal 71.1/popl1;z/sis writ/1 /z‘nIumefrir* (lvfm'mimI.— fir)-ns on human azlnlfs am] on animals Rasmussen (’24) found the adult l1uma11 hypophysis to be approximately 72 per cent pa.rs anterior, 18 per cent pars nervosa, 2 per cent pars intermedia, a11d 8 per cent capsule. These relative values when compared to t.l1ose for the hypophysis of the newborn are obviously in fair agfreemeiit. The capsule of the hypophysis of the newborn a11d fetus is relatively much smaller in amount and more difficult to approximate than in the adult. For this reason its relative volume was 11ot determined. For a eomparison of the relative values of the lobes of the adult human gland with those of the newborn hypophysis it is necessary to express the former in terms of the three lol)es only. The pars anterior of the adult hypophysis comprises about 78 per cent of the gland volume, the pars intermedia about 2 per eent, and the pars nervosa about 20 per cent. The relative volumes of the lobes of the hypophysis of the newborn have approximately the same values. From this it is evident that the adult relationships of the lobes of the gland are established at about the time of birth or early in postnatal life.

Jackson (’17) found the hypophysis of the albino rat to be quite variable as regards relative volumes of the lobes. A comparison of the figures given by him shows that the relative volumes of the epithelial and neural elements of the gland of the adult rat and those of the human embryonic hypophysis are similar. In the latter material the total epithelial portions are approximately 90 to 95 per cent of the gland volume, while the relative volume of the posterior lobe is about 5 to 10 per cent. It is evident from the relative volumes of the ;,rland lobes for the albino rat that the partes anterior and intermedia comprise about 92 or 93 per cent of the total gland Weight and the posterior lobe approximately 7 or 8 per cent. A comparison of the pars intermedia of the hypophysis of the rat with that of the human does not show such close agreement.

Rasmussen (’21) analyzed the hypophysis of the woodchuck with regards to the relative Volumes of each of the lobes. He found the pars anterior to comprise about 46 per cent of the entire organ (before and during hibernation), the pars intermedia about 2.46 per cent, and the remaining relative volume to be pars nervosa. These proportions are, for the most part, quite different from those found in the human hypophysis at any stage in its development.

Bjorkman (’15) found the hypophysis of the rabbit to be approximately 70 per cent pars anterior, 17 per cent pars nervosa, and 13 per cent pars intermedia. The intermediate lobe comprises considerable more of the gland than in any of the other forms analyzed.

Summary

The results of this study may be summarized as follows:

1. The growth in weight of the hypophysis during the embryonic and early fetal periods is Very rapid. It follows the course of a shallow concave curve which rises rapidly in specimens of 50 to 100 mm. (crown-rump).
2. The growth in weight of the hypophysis and its lobes during the fetal period resembles the general type of growth characteristic of the body as a whole as Well as certain of the organs. Total gland weight and weights of the partes anterior and intermedia follow a curve of growth similar to those for the volumes of the eyeball, midbrain, and spinal cord. The fetal growth of the pars nervosa in weight resembles the curves for the optic nerve and cerebrum Volumes and total body weight.
3. At birth the total weight of the hypophysis is about 107 mg. The calculated weights of the partes anterior, intermedia, and nervosa at this time are, respectively, 83.4 mg., 2.05 mg., and 20.7 mg.
4. The diameters of the hypophysis increase slowly during the fetal period. The anteroposterior and Vertical diameters increase at approximately the same rate, the transverse diameter grows more slowly.
5. The calculated transverse diameter for the hypophysis of a full-term fetus is 0.79 cm., the anteroposterior diameter is 0.57 cm., and the Vertical diameter is 0.49 cm.
6. The transverse diameter is the largest one of the hypophyseal fossa, and increases more in fetuses ranging from 20 to 55 cm. in total body length than do the anteroposterior and vertical diameters.
7. The calculated transverse diameter of the hypophyseal fossa at birth is 0.89 cm., the anteroposterior diameter is 0.54 cm., and the vertical diameter is 0.29 cm.
8. The relative volumes of the lobes of the hypophysis show a gradual change during prenatal life. rfhe partes anterior and intermedia comprise relatively more of the gland in embryonic and early fetal life than at birth. The pars nervosa gradually increases in relative volume during prenatal life.
9. The hypophysis of the full—term fetus is roughly 78 per cent pars anterior, 2 per cent pars intermedia, and 20 per cent pars nervosa.

Bibliography

BJGRKMAN, H. 1915-1916 Bidrag till hypofysens aldersanatomi hos kaninen. Upsala Lakareforenings Forhandlingar, N. F., Bandet 21, pp. 49-108. (Cited by Rasmussen, A. T., 1921.)

COMTE, L. 1898 Contribution a 1’étudc de l’hypophyse humaine et de ses relations avec le corps thyreoirle. Beitr. z. path. Anat. u. z. allg. Path., Bd. 23, s. 9o—i10.

CUTORE, G. 1910 Il corpo pineale di alcuni mammiferi. Arch. Ital. di Anat. e di Embriol., vol. 9, pp. 402-464.

DUNN, H. L. 1921 The growth of the central nervous system in the human fetus as expressed by graphic analysis and empirical formulae. Jour. Comp. Ncur., vol. 33, pp. 405-491.

HAMMAR, J. A. 1914 Methode, die Monge dor Rinde und des Marks der Thymus, sowie die Anzahl und die Grosse der Hassallschen Kiirper zahlenmissig festzustellen. Zeitschrift f. angewandtc Anatomie u. Konstitutionslehre, Ed. 1, S. 311-396.

JACKSON, C. M. 1917 Effects of inanition and refeeding upon the growth and structure of the hypophysis in the albino rat. Am. Jour. Anat., vol.

‘ 21, pp. 321-358.

LIPKA, J. 1918 Graphical and mechanical computation, pp. 122~127. New York.

LUCIEN, M. 1911 Les poids, les dimensions et la forme générale de l’hypophysc hurnaine aux diiférents ages de la vie. Compt. Bend. (le l’Ass. (1. Anat., Treiz. Reun., T. 13, pp. 147-158.

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Cite this page: Hill, M.A. (2024, April 16) Embryology Paper - Growth of the human prenatal hypophysis and the hypophyseal fossa. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Paper_-_Growth_of_the_human_prenatal_hypophysis_and_the_hypophyseal_fossa

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