Historically, this endocrine gland was called the "pituitary" as it was originally thought to produce mucous that discharged through the nose. We now know that this is not the function of the pituitary, or hypophysis which is an endocrine gland links the brain to peripheral endocrine organs and systems of the body through several specific hormones. The developmental origin of the hypophysis is also unique, epithelial origins from neural ectoderm (posterior) and from surface ectoderm (anterior).
During development, the boundary epitheilal ectoderm in the roof of the pharynx forms a pocket (Rathke's pouch) that comes into contact with the ectoderm of developing brain. Rathke's pouch is named after German embryologist and anatomist Martin Heinrich Rathke (1793 1860).
Embryonic and Fetal Pituitary
Anatomically, the pituitary has 2 main parts posterior, or neurohypophysis and anterior, or adenohypophysis (the pars distalis, pars intermedia, and pars tuberalis). Between the two
a specialized vascular (portal) system allows communication from the brain to peripheral endocrine organs and other systems.
The pituitary is located within the pituitary fossa of the sphenoid bone, anterior to the lamina terminalis and superior to the pharynx. The shape of the bone surrounding the pituitary led to the naming sella turcica (Latin sella = saddle, turcica = Turkish), as it resembled a saddle shape.
Pit1 (pituitary-specific transcription factor) is a transcription factor important for pituitary development and muations in this gene can lead to abnormalities in pituitary development and hormone production. (More? Molecular Development Factors - Pit)
Page Links: Introduction | Some Recent Findings | Reading | Development Overview | Serial Images | Blood Vessel Development | Histology | Abnormalities | Molecular Development | Genes | WWW Links | References | Glossary
Gleiberman AS, Michurina T, Encinas JM, Roig JL, Krasnov P, Balordi F, Fishell G, Rosenfeld MG, Enikolopov G. Genetic approaches identify adult pituitary stem cells. Proc Natl Acad Sci U S A. 2008 Apr 29;105(17):6332-7.
"We report the presence (in mouse) of nestin-expressing adult stem cells in the perilumenal region of the mature anterior pituitary and, using genetic inducible fate mapping, demonstrate that they serve to generate subsets of all six terminally differentiated endocrine cell types of the pituitary gland."
Nakakura T, Yoshida M, Dohra H, Suzuki M, Tanaka S. Gene expression of vascular endothelial growth factor-A in the pituitary during formation of the vascular system in the hypothalamic-pituitary axis of the rat. Cell Tissue Res. 2006 Apr;324(1):87-95
"....study suggests in the rat that VEGF-A (Vascular Endothelial Growth Factor A) is involved in the development of the primary capillaries and in the vascularization of the pars distalis, but not in the portal vessels since the formation of portal vessels begins at E13.5, before the appearance of VEGF-A in the rostral region of the pars distalis."
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Historic image of the pituitary |
Human Timeline:
Ectoderm- ectoderm roof of stomodeum, neuroectoderm of diencephalon Adenohypophysis anterior pituitary, glandular (pars anterior, pars intermedia, pars tuberalis) Neurohypophysis posterior pituitary, nervous (pars nervosa)
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Stage 13/14 Embryo
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B1: Dorsal portion of hypopharyngeal eminence. Rathke's pouch derived from ectoderm anterior to the buccopharyngeal membrane ( rudimentary adenohypophysis). |
B2: Rathke's pouch. Thyroid rudiment (cords) arrowed dark spots near midline. |
B3: Rudimentary thyroid ventral to aortic sac (also seen in B2, ventral to the hypopharyngeal eminence). |
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G7: (Close to midline in head region). Forebrain, midbrain, hindbrain (with thin roof). Arrowed Rathke's pouch. Floor of pharynx with foramen caecum (the tongue has not yet formed). |
Stage 22 Human Embryo
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B1 section at optic nerve level just above hypophysis |
B2 section through hypophysis at level shown in High Power images |
B3 section through lower part of hypophysis |
Stage 22 Human Embryo (High Power)
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HPB2 cross-section of developing Hypophysis |
HPA7 Location of this Section |
Human Fetus (Week 10)
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Section D showing Hypophysis behind lamina terminalis |
Section C showing the hypophyseal fossa |
pars distalis - vascularized by hypophysial portal vessels
A study in rats has identified the role of a known regulator of blood vessel development (Vascular Endothelial Growth Factor, VEGF) in the development of the pituitary portal vascular system. Nakakura T, Yoshida M, Dohra H, Suzuki M, Tanaka S. Gene expression of vascular endothelial growth factor-A in the pituitary during formation of the vascular system in the hypothalamic-pituitary axis of the rat. Cell Tissue Res. 2006 Apr;324(1):87-95
"The primary capillaries extended along the developing pars tuberalis, whereas the portal vessels penetrated into the pars distalis at E15.5 (rat) and subsequently expanded into the lobe to connect with the secondary capillary plexus, emerging in the pars distalis. ....study suggests that VEGF-A (Vascular Endothelial Growth Factor A) is involved in the development of the primary capillaries and in the vascularization of the pars distalis, but not in the portal vessels since the formation of portal vessels begins at E13.5 (rat), before the appearance of VEGF-A in the rostral region of the pars distalis."
The pars distalis is vascularized by hypophysial portal vessels that arise from the capillary beds in the median eminence of the hypothalamus (Murakami et al. 1987), and this hypophyseal portal system provides an important link for carrying hormonal information from the central nervous system to the pituitary. The capillaries of the pituitary gland are characterized by richly fenestrated endothelia.
The pituitary has a very interesting histological structure based initially upon its unique embryonic origin of two main halves, the presence of neural processes, cellular and vascular composition.
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Adenohypophysis |
Adenohypophysis |
Neurohypophysis |
Click images above to enlarge |
(Images: Lutz Slomianka, UWA Blue Histology) |
Now look at the slides from UNSW Virtual Slidebox BGD (B) Histology of the HP Axis and then and the external Virtual Slidebox Human Pituitary and Unknown Species Pituitary which include brief descriptions of the tissue sections.
Those with access to the Anatomy slide set should also look at Slide 25 Pituitary (Hypophysis) human Tri-PAS stain and Slide 26 Pituitary (Hypophysis) ox Picro-Mallory stain.
Links: UWA Blue Histology - Pituitary | Virtual Slide - Endocrine | CSU - Histology of the Adenohypophysis | CSU - Histology of the Neurohypophysis |
Anatomical abnormalities asssociated with the Rathke's pouch include a craniopharyngeal canal, from the anterior part of the fossa hypophyseos of the sphenoid bone to the under surface of the skull. The stomodeal end may also be present at the junction of the septum of the nose with the palate.
Abnormal functional development of the pituitary can lead to a wide range of other organ diseases due to the effect of hormones released from the pituitary on many other endocrine and non-endocrine organs (For example: dwarfism, hypothyroidism). (More? NIH Genes and Disease Chapter 41 - Endocrine)
There are several abnormalities associated with abnormal levels of the hormonal output of the pituitary due to the development of pituitary tumours (adenomas).
Growth hormone (GH) adenomas, which are benign pituitary tumors lead to chronic high GH output levels, that may lead to acromegaly.
Cushing's disease caused either by a pituitary adenoma produces excess adrenocorticotropic hormone (ACTH, corticotropin) or due to ectopic tumors secreting ACTH or corticotropin-releasing hormone (CRH).
Pituitary Adenoma Classification
Classification can be applied using specific criteria (clinical presentation, biochemical data, histology of growth pattern, tinctorial characteristics, proliferative activity, immunohistology marker expression, ultrastructure and molecular biology). The current classification used is the World Health Organization classification of 2000 recently updated in 2004.
Molecular markers
Pituitary-specific transcription factor 1 - (Pit1) in GH-, prolactin- or TSH-secreting adenomas. (More? Molecular Development Factors - Pit | OMIM - Pit1)
T-box factor 19 - (TBX19 or TPIT) in ACTH-producing adenomas. (More? OMIM - TBX19)
Splicing Factor 1 - (SF1) in gonadotroph, null cell and oncocytic adenomas. (More? OMIM - SF1)
Links: OMIM - ACTH Deficiency | Pituitary Adenoma scan | 1999 OMIM Search Pituitary
Search PubMed: pituitary adenoma | Cushing's disease | (More? Search PubMed Pituitary development terms)
Scully KM, Rosenfeld MG. Pituitary development: regulatory codes in mammalian organogenesis. Science. 2002 Mar 22;295(5563):2231-5.
"During mammalian pituitary gland development, distinct cell types emerge from a common primordium. Appearance of specific cell types occurs in response to opposing signaling gradients that emanate from distinct organizing centers. These signals induce expression of interacting transcriptional regulators, including DNA binding-dependent activators and DNA binding-independent transrepressors, in temporally and spatially overlapping patterns. Together they synergistically regulate precursor proliferation and induction of distinct cell types. Terminal cell type differentiation requires selective gene activation strategies and long-term active repression, mediated by cell type-specific and promoter-specific recruitment of coregulatory complexes. These mechanisms imply the potential for flexibility in the ultimate identity of differentiated cell types."
Kioussi C, O'Connell S, St-Onge L, Treier M, Gleiberman AS, Gruss P, Rosenfeld MG. Pax6 is essential for establishing ventral-dorsal cell boundaries in pituitary gland development. Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14378-82.
"The transcription factor Pax6 (paired homeodomain) has been shown to be expressed transiently in the dorsal portion of the developing pituitary before the ventral/dorsal appearance of specific cell types. Transient dorsal expression of Pax6 could establish the boundary between dorsal and ventral cell types, based on the inhibition of Shh ventral signals."
PIT1 Pituitary-Specific Transcription Factor 1 - transcription factor responsible for pituitary development and hormone expression in mammals. OMIM 173110 | Gene Map Locus: 3p11 | is a pituitary-specific transcription factor responsible for pituitary development and hormone expression in mammals and is a member of the POU family of transcription factors that regulate mammalian development.
PitX1 Paired-Like Homeodomain Transcription Factor 1 - transcription factor expressed in pituitary primordium. Member of bicoid-related vertebrate homeobox genes. OMIM 602149 | Gene Map Locus: 5q31 |
PitX2 Paired-Like Homeodomain Transcription Factor 2 - transcription factor expressed in pituitary primordium and other anterior structures, including the eye Member of bicoid-related vertebrate homeobox genes. OMIM 601542 | Gene Map Locus: 4q25-q26 |
TPIT T-box transcription factor Pituitary OMIM 604614 | Gene Map Locus: 1q23-q24 |
VEGF Vascular Endothelial Growth Factor - mitogen growth factor for vascular endothelial cells. Role in pituitary vascular development. OMIM 192240 | Gene Map Locus: 1q23-q24 |
Links: Journals | Online Textbooks | Search Textbooks | Reviews | 1999 Refs | Search PubMed | Glossary
Endocrinology: An Integrated Approach Nussey, S.S. and Whitehead, S.A. Oxford, UK: BIOS Scientific Publishers, Ltd; 2001. table of Contents
NIH Genes & Disease Chapter 41 - Endocrine
Developmental Biology (6th ed) Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000.
Stages along the hypothalamus-pituitary-thyroid axis of salamanders
Molecular Biology of the Cell (4th Edn) Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter. New York: Garland Publishing; 2002.
table 15-1. Some Hormone-induced Cell Responses Mediated by Cyclic AMP
Alternative processing pathways for the prohormone proopiomelanocortin
Clinical Methods (3rd Edn) Walker, H.K.; Hall, W.D.; Hurst, J.W.; editors Stoneham (MA).
Health Services/Technology Assessment Text (HSTAT) Bethesda (MD): National Library of Medicine (US), 2003 Oct.
Search NLM Online Textbooks- "pituitary development" : Endocrinology | Molecular Biology of the Cell | The Cell- A molecular Approach
Reviews
Scully KM, Rosenfeld MG. Pituitary development: regulatory codes in mammalian organogenesis. Science. 2002 Mar 22;295(5563):2231-5.
Rosenfeld MG, Briata P, Dasen J, Gleiberman AS, Kioussi C, Lin C, O'Connell SM, Ryan A, Szeto DP, Treier M. Multistep signaling and transcriptional requirements for pituitary organogenesis in vivo. Recent Prog Horm Res. 2000;55:1-13; discussion 13-4
Kioussi C, Carriere C, Rosenfeld MG. A model for the development of the hypothalamic-pituitary axis: transcribing the hypophysis. Mech Dev. 1999 Mar;81(1-2):23-35.
Articles
Nakakura T, Yoshida M, Dohra H, Suzuki M, Tanaka S. Gene expression of vascular endothelial growth factor-A in the pituitary during formation of the vascular system in the hypothalamic-pituitary axis of the rat. Cell Tissue Res. 2006 Apr;324(1):87-95
Kioussi C, O'Connell S, St-Onge L, Treier M, Gleiberman AS, Gruss P, Rosenfeld MG. Pax6 is essential for establishing ventral-dorsal cell boundaries in pituitary gland development. Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14378-82.
Treier M, O'Connell S, Gleiberman A, Price J, Szeto DP, Burgess R, Chuang PT, McMahon AP, Rosenfeld MG. Hedgehog signaling is required for pituitary gland development. Development. 2001 Feb;128(3):377-86.
Search PubMed
Search Aug2005 "pituitary development" 10,998 reference articles of which 2,121 were reviews.
Search PubMed: term = pituitary+development | term = hypophysis+development | term = adenohypophysis+development | term = neurohypophysis+development
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arginine vasopressin - (vasopressin, AVP) A hypothalamus neuropeptide hormone stored in the posterior pituitary (neurohypophysis). The hormones actions include: stimulate liver glycogenolysis, contraction of vascular smooth muscle cells and kidney mesangial cells, antidiuresis in the kidney, and aggregation of platelets. Also in mouse, this hormone has been shown to promote maternal behavior. (More? Endocrine Development - Hypothalamus | OMIM arginine vasopressin)
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The developing pituitary gland has an extrordinary embryonic origin, from two separate epithelia extending toward each other. The anterior pituitary also has an interesting early developmental stage when it initially and transiently forms a pocket (Rathke's) on the roof of the developing oral cavity.
While all endocrine organs are vascularized, the pituitary gland has a unique vascular system communicationg between the posterior and anterior parts. Recent research has looked into the growth factor regulation of this vascular system.
Something old, something new....listen to where the term "hormone" came from in the linked podcast.
Please email Dr Mark Hill if you wish to make a comment about this current project.
