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=The development of the mammalian pituitary and its morphological significance=
=The Development of the Mammalian Pituitary and its Morphological Significance=


By P. T. HERRING. (From
By P. T. Herring
the Physiology Department, University of Edinburgh.)


(Received for publication 11th February 1908.)
From the Physiology Department, University of Edinburgh
 
Received for publication 11th February 1908


==Introduction==
==Introduction==


THE development of the pituitary body has been a favourite subject of
The development of the pituitary body has been a favourite subject of research by embryologists. Its position in the embryo, forming as it were a meeting-point for the anterior end of the neural canal, buccal invagination, archénteron, and notochord, gives to the pituitary an importance, the significance of which has been the object of much speculation. Some authorities have looked upon its relations to these structures as more or less accidental; others have attached great Weight to them. Kupffer, indeed, regarded the pituitary body as an important key to the phylogeny of the vertebrate head. The morphological significance of the pituitary is also of interest from a
research by embryologists. Its position in the embryo, forming as it were
physiological point of view, and some of the theories which have been advanced regarding it will be briefly discussed in this paper.
a meeting-point for the anterior end of the neural canal, buccal invagination,
archénteron, and notochord, gives to the pituitary an importance, the significance of which has been the object of much speculation. Some authorities
have looked upon its relations to these structures as more or less accidental;
others have attached great Weight to them. Kupffer, indeed, regarded the
pituitary body as an important key to the phylogeny of the vertebrate head.
The morphological significance of the pituitary is also of interest from a
physiological point of view, and some of the theories which have been
advanced regarding it will be briefly discussed in this paper.


Nearly all the work that has been done on the development of the


“pituitary body has been concerned with its mode of origin and with the
Nearly all the work that has been done on the development of the “pituitary body has been concerned with its mode of origin and with the early stages of its growth. The later stages, although probably of greater physiological importance, have been comparatively neglected. The differentiation of the epithelium of the anterior lobe, the relations of epithelium to the nervous tissue of the posterior lobe, and the extraordinary differences
 
early stages of its growth. The later stages, although probably of greater
physiological importance, have been comparatively neglected. The differentiation of the epithelium of the anterior lobe, the relations of epithelium
to the nervous tissue of the posterior lobe, and the extraordinary differences
in the vascularity of its several parts are all features which need investigation. Its development in mammals has been followed chiefly in animals in
in the vascularity of its several parts are all features which need investigation. Its development in mammals has been followed chiefly in animals in
which the posterior lobe of the pituitary becomes a solid structure at a
which the posterior lobe of the pituitary becomes a solid structure at a
Line 39: Line 27:
pituitary body of the cat forms the basis of the description in this paper.
pituitary body of the cat forms the basis of the description in this paper.
The embryos of man, ox, and pig, which furnish a different type of pituitary,
The embryos of man, ox, and pig, which furnish a different type of pituitary,
have also been eizamined, and some of the more important features presented
have also been eizamined, and some of the more important features presented by them receive attention.
by them receive attention.
 
 


==Historical==
==Historical==


 
The pituitary body was at one time thought to be wholly derived from the brain, but Rathke (26) in 1838 described the invagination of mucous membrane which is now known as Rathke’s pouch. Rathke rightly assigned to this pouch the origin of the epithelial portion of the pituitary, but was mistaken in believing it to be derived from the entoderm of the fore-gut. His view was not at once accepted. Reichert (28) failed to find
The pituitary body was at one time thought to be wholly derived from
 
-the brain, but Rathke (26) in 1838 described the invagination of mucous
 
membrane which is now known as Rathke’s pouch. Rathke rightly
assigned to this pouch the origin of the epithelial portion of the pituitary,
but was mistaken in believing it to be derived from the entoderm of the
fore—gut. His view was not at once accepted. Reichert (28) failed to find
the invagination, and put forward the theory that the epithelial portion of
the invagination, and put forward the theory that the epithelial portion of
the pituitary is a structure of mesodermic origin derived from the anterior
the pituitary is a structure of mesodermic origin derived from the anterior
Line 73: Line 50:




The posterior lobe of the pituitary was at first believed to represent the
The posterior lobe of the pituitary was at first believed to represent the anterior extremity of the brain (v. Baer (2)). Gotte (12) showed that in amphibians this is not the case, the infundibulum being a later formation. The researches of Mihalkovics (21), van Wijhe (35), Kupffer (20), and others have demonstrated that the infundibulum cannot be regarded as the representative of the anterior end of the brain axis; it is an outgrowth of the “ Zwischenhirn ” or thalamencephalon.
anterior extremity of the brain (v. Baer (2)). Gotte (12) showed that in
amphibians this is not the case, the infundibulum being a later formation.
The researches of Mihalkovics (21), van Wijhe (35), Kupffer (20), and
others have demonstrated that the infundibulum cannot be regarded as the
representative of the anterior end of the brain axis; it is an outgrowth
of the “ Zwischenhirn ” or thalamencephalon.




The proximity of the anterior end of the notochord to the developing
The proximity of the anterior end of the notochord to the developing pituitary body led to the belief, not only that the notochord enters into the
pituitary body led to the belief, not only that the notochord enters into the
structure of the pituitary, but that it also exercises a mechanical influence
structure of the pituitary, but that it also exercises a mechanical influence
upon the formation of the infundibulum. Both His and Dursy considered
upon the formation of the infundibulum. Both His and Dursy considered
Line 97: Line 67:
this manner.
this manner.


The most complete account of the early development of the pituitary
 
body is that given by Mihalkovics (21), who investigated the subject in
The most complete account of the early development of the pituitary body is that given by Mihalkovics (21), who investigated the subject in
rabbit and chick embryos. Mihalkovics found that the anterior lobe is
rabbit and chick embryos. Mihalkovics found that the anterior lobe is
developed from Rathke’s pouch, which, in mammals as in amphibians, is
developed from Rathke’s pouch, which, in mammals as in amphibians, is
Line 124: Line 94:
of the pituitary body.
of the pituitary body.


The main conclusions of Mihalkovics’ researches have been confirmed
 
by Kolliker (16), Kraushaar (18), Minot (22), Kupffer (19), Salzer (33),
The main conclusions of Mihalkovics’ researches have been cofirmed by Kolliker (16), Kraushaar (18), Minot (22), Kupffer (19), Salzer (33),
and others. Kupf f er described an additional origin of part of the anterior
and others. Kupffer described an additional origin of part of the anterior lobe of the pituitary from the entoderm of the fore-gut. According to
lobe of the pituitary from the entoderm of the fore-gut. According to
Kupffer, the pituitary body of amphibians is built up from three separate
Kupf fer, the pituitary body of amphibians is built up from three separate
sources: part of the epithelial lobe is derived from Rathke’s pouch, and
sources: part of the epithelial lobe is derived from Rathke’s pouch, and
part from the anterior end of the fore-gut, while the infundibulum is of
part from the anterior end of the fore-gut, while the infundibulum is of
Line 145: Line 114:




Kupff er came to the conclusion that the intimate relationship between
Kupffer came to the conclusion that the intimate relationship between infundibulum, mouth, and intestine is not an accidental one, but denotes an ancestral communication between the brain tube and the anterior part of
infundibulum, mouth, and intestine is not an accidental one, but denotes an
ancestral communication between the brain tube and the anterior part of
the intestinal canal. A structure resembling in many respects the early
the intestinal canal. A structure resembling in many respects the early
stages of development of the vertebrate pituitary is found in Ascidians, and
stages of development of the vertebrate pituitary is found in Ascidians, and
Line 184: Line 151:
to be a secondary structure and not related to the origin of the hypophysis.
to be a secondary structure and not related to the origin of the hypophysis.
He also states that the anterior lobe of the pituitary of mammals and
He also states that the anterior lobe of the pituitary of mammals and
other vertebrates is a tubular gland which pours a secretion into the
other vertebrates is a tubular gland which pours a secretion into the subdural space. The latter statement has not been confirmed by subsequent observers. Gaskell (9) quotes Haller’s results in support of the
subdural space. The latter statement has not been confirmed by subsequent observers. Gaskell (9) quotes Haller’s results in support of the
 
 





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Herring PT. The histological appearances of the mammalian pituitary body. (1908) Quar. Jour. Ex. Physiol. 1: 121-159.

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The Development of the Mammalian Pituitary and its Morphological Significance

By P. T. Herring

From the Physiology Department, University of Edinburgh

Received for publication 11th February 1908

Introduction

The development of the pituitary body has been a favourite subject of research by embryologists. Its position in the embryo, forming as it were a meeting-point for the anterior end of the neural canal, buccal invagination, archénteron, and notochord, gives to the pituitary an importance, the significance of which has been the object of much speculation. Some authorities have looked upon its relations to these structures as more or less accidental; others have attached great Weight to them. Kupffer, indeed, regarded the pituitary body as an important key to the phylogeny of the vertebrate head. The morphological significance of the pituitary is also of interest from a physiological point of view, and some of the theories which have been advanced regarding it will be briefly discussed in this paper.


Nearly all the work that has been done on the development of the “pituitary body has been concerned with its mode of origin and with the early stages of its growth. The later stages, although probably of greater physiological importance, have been comparatively neglected. The differentiation of the epithelium of the anterior lobe, the relations of epithelium to the nervous tissue of the posterior lobe, and the extraordinary differences in the vascularity of its several parts are all features which need investigation. Its development in mammals has been followed chiefly in animals in which the posterior lobe of the pituitary becomes a solid structure at a comparatively early stage. In the cat, this lobe remains hollow throughout development, and presents peculiarities of morphological interest which are not found in the pituitaries of other animals. The structure of the posterior lobe in the cat is also of a simpler character, and the nature and arrangement of the cells found in it can be interpreted more readily than in the case of those animals which possess a solid lobe. For these reasons the pituitary body of the cat forms the basis of the description in this paper. The embryos of man, ox, and pig, which furnish a different type of pituitary, have also been eizamined, and some of the more important features presented by them receive attention.

Historical

The pituitary body was at one time thought to be wholly derived from the brain, but Rathke (26) in 1838 described the invagination of mucous membrane which is now known as Rathke’s pouch. Rathke rightly assigned to this pouch the origin of the epithelial portion of the pituitary, but was mistaken in believing it to be derived from the entoderm of the fore-gut. His view was not at once accepted. Reichert (28) failed to find the invagination, and put forward the theory that the epithelial portion of the pituitary is a structure of mesodermic origin derived from the anterior end of the notochord. His (14«) lent additional support to Reichert’s view, but made no special investigations of the subject himself. Both Rathke (27) and Reichert (29) subsequently changed their opinions, the latter believing the anterior lobe to arise from a proliferation of the cells of the pia mater. Dursy (8) sought to unite the original view of Rathke with that of Reichert and His, and described the origin of the epithelium of the pituitary from the fore—gut, and the origin of its vascular stroma from the tissue of the head of the notochord. W. Miiller (23) demonstrated that the anterior lobe of the pituitary is derived from Rathke’s pouch, but fell into the same error as Rathke and Dursy in believing it to be of entodermic origin. The later researches of Gotte (12) and Balfour (3) showed that the pouch described by Rathke is derived, not from the fore-gut, but from the epithelium of the buccal cavity immediately in front of the oral plate. The pouch is now recognised as an ectodermic structure.


The posterior lobe of the pituitary was at first believed to represent the anterior extremity of the brain (v. Baer (2)). Gotte (12) showed that in amphibians this is not the case, the infundibulum being a later formation. The researches of Mihalkovics (21), van Wijhe (35), Kupffer (20), and others have demonstrated that the infundibulum cannot be regarded as the representative of the anterior end of the brain axis; it is an outgrowth of the “ Zwischenhirn ” or thalamencephalon.


The proximity of the anterior end of the notochord to the developing pituitary body led to the belief, not only that the notochord enters into the structure of the pituitary, but that it also exercises a mechanical influence upon the formation of the infundibulum. Both His and Dursy considered that a close union between the notochord and the wall of the cerebral vesicle is the dominating factor in the development of the infundibulum, but were not agreed as to the exact manner in which this is brought about. W. Muller believed that the head of the notochord anchors a portion of the wall of the brain, and that with the growth of the surrounding tissues the rest of the brain is carried forwards, leaving a diverticulum of its wall, the infundibulum, attached to the notochord. The attachment is subsequently dissolved by a proliferation of connective tissue cells. Mihalkovics (21) and others showed that the head of the notochord does not come into immediate relationship with the brain, and cannot therefore act upon it in this manner.


The most complete account of the early development of the pituitary body is that given by Mihalkovics (21), who investigated the subject in rabbit and chick embryos. Mihalkovics found that the anterior lobe is developed from Rathke’s pouch, which, in mammals as in amphibians, is of ectodermic origin. The beginning of the pouch or hypophysial angle lies in front of the oral plate, Where the epidermis bends round the base of the brain to the nasal mucosa. In the rabbit, Mihalkovics states that the end of the notochord is in contact with the epidermis at the back of Rathke’s pouch. When the oral plate ruptures, its upper stump, containing in its upper part the head of the notochord, bends forward and narrows the mouth of the epithelial pouch, leading to the formation of a definite sac—the hypophysial sac. The wall of the sac presses upon the base of the anterior brain vesicle, giving rise at its upper extremity to a fold in the wall of the brain which becomes the primitive infundibulum. Mihalkovics denied that the end of the notochord is ever united to the wall of the fore-brain; it does not enter into the formation of the infundibulum at all, but has some influence upon the hypophysial sac, by preventing this from extending backwards. The primitive infundibular process comprises the surrounding tissue of the tuber cinereum as well as the origin of the infundibulum, and the true infundibulum is formed at a later stage by its own growth from a portion of the primitive infundibular process. Mihalkovics made a careful investigation of the relations of the notochord, and found that its head touches the lower part of the posterior wall of the hypophysial sac in rabbits, but is placed at a higher level in birds; it exercises no traction upon the sac in either, and, beyond presenting a barrier to the backward growth of the sac, takes no part in the formation of the pituitary body.


The main conclusions of Mihalkovics’ researches have been cofirmed by Kolliker (16), Kraushaar (18), Minot (22), Kupffer (19), Salzer (33), and others. Kupffer described an additional origin of part of the anterior lobe of the pituitary from the entoderm of the fore-gut. According to Kupffer, the pituitary body of amphibians is built up from three separate sources: part of the epithelial lobe is derived from Rathke’s pouch, and part from the anterior end of the fore-gut, while the infundibulum is of brain origin. In mammals, e. g. the sheep, the hypophysial pouch appears behind the “ Riechplakode.” Behind this and ventral to it is a swelling, the “Haftscheibe,” which is an important larval organ in Lepidosteus. Then comes the double-layered oral plate (“ Rachenh ant”), and behind this an outgrowth of entoderm directed dorsally and forwards, known as Seessel’s pouch. The third portion of the pituitary, the cerebral, appears later, after the disappearance of the oral plate and median “Riechplakode.” In the next stage the growth of entoderm increases, but is cut off from Seessel’s pouch; no cavity is to be found in it, and the end of the notochord remains in contact with it. The infundibulum now to grow. In the older embryos, e. g. 11—mm. sheep, the entodermic part degenerates and appears as a string-like appendage of the notochord; it eventually disappears, and does not enter into the formation of the adult mammalian pituitary.


Kupffer came to the conclusion that the intimate relationship between infundibulum, mouth, and intestine is not an accidental one, but denotes an ancestral communication between the brain tube and the anterior part of the intestinal canal. A structure resembling in many respects the early stages of development of the vertebrate pituitary is found in Ascidians, and is known as the subneural gland. J ulin (15) in 1881 pointed out that this gland is probably homologous with the hypophysis of higher vertebrates, and since then it has been frequently spoken of as the Ascidian hypophysis. Kupffer believes that the direct ancestors of vertebrates showed the same relations as are seen to—day in the tailed Ascidian larva. In a scheme of the ancestral vertebrate he describes the mouth (“ Palaeostoma ”) opening dorsally in front of the brain. The brain tube is in communication with the anterior part of the intestine by a canal running through the base of the anterior brain vesicle. This canal has developed upon it a subcerebral gland. Ventral to the palaeostoma is the “ Haftorgan ” on the anterior pole of the body. In the course of development the new vertebrate mouth (Neostoma) is formed, in agreement with Dohrn’s hypothesis, from a pair of gill-clefts below the “Haftorgan.” The part of the intestine between the old and the new mouth, or preoral intestine, is reduced, but persists to a certain extent in some vertebrates. The palaeostoma is lined by epidermis, and its representative in vertebrates is Rathke’s pouch; it also forms the outer part of the nasal duct (“ Nasenrachengang ”) of Myxine, and the entire nasal duct of Petromyzon. The remains of the canalis neurentericus anterior, with its appertaining glands, are to be seen in the infundibular process and saccus vasculosus. In mammals, the only representative of the preoral intestine is the transitory appearance of the solid mass of cells formed from Seessel’s pouch, but in amphibians it persists as part of the anterior lobe of the pituitary.


Kupffer’s views on the morphological significance of the pituitary body have not met with general acceptance. Willey (36) states that the present relation of the hypophysis to the infundibulum in the craniates, however intimate it may be in some cases, is, nevertheless, incidental and secondary. Willey believes that the hypophysis arose in connection with a functional neuropore. B. Haller (13) criticises Kupf f er’s results and differs from him in many important particulars. He believes the nasal duct of Cyclostomata to be a secondary structure and not related to the origin of the hypophysis. He also states that the anterior lobe of the pituitary of mammals and other vertebrates is a tubular gland which pours a secretion into the subdural space. The latter statement has not been confirmed by subsequent observers. Gaskell (9) quotes Haller’s results in support of the




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