Endocrine - Pituitary Development
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, with 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).
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.
Maternal pituitary also increases in size during pregnancy, due mainly to hyperplasia of the prolactin secreting cells (lactotrophs), in preparation for lactation after birth.
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Some Recent Findings
|More recent papers|
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Yan Yan, Xiaofeng Zhou, Zui Pan, Jianjie Ma, James A Waschek, Emanuel DiCicco-Bloom Pro- and anti-mitogenic actions of pituitary adenylate cyclase-activating polypeptide in developing cerebral cortex: potential mediation by developmental switch of PAC1 receptor mRNA isoforms. J. Neurosci.: 2013, 33(9);3865-78 PMID:23447598 Pierluigi Marzuillo, Anna Grandone, Ruggero Coppola, Domenico Cozzolino, Adalgisa Festa, Federica Messa, Caterina Luongo, Emanuele Miraglia Del Giudice, Laura Perrone Novel cAMP binding protein-BP (CREBBP) mutation in a girl with Rubinstein-Taybi syndrome, GH deficiency, Arnold Chiari malformation and pituitary hypoplasia. BMC Med. Genet.: 2013, 14(1);28 PMID:23432975 T V Novoselova, D Jackson, D C Campbell, A J L Clark, L F Chan Melanocortin receptor accessory proteins in adrenal gland physiology and beyond. J. Endocrinol.: 2013, 217(1);R1-11 PMID:23418361 Margarita González del Pliego, Elsa Aguirre-Benítez, Karina Paisano-Cerón, Irene Valdovinos-Ramírez, Carlos Rangel-Morales, Verónica Rodríguez-Mata, Carmen Solano-Agama, Dolores Martín-Tapia, María Teresa de la Vega, Miguel Saldoval-Balanzario, Javier Camacho, María Eugenia Mendoza-Garrido Expression of Eag1 K+ channel and ErbBs in human pituitary adenomas: cytoskeleton arrangement patterns in cultured cells. Int J Clin Exp Pathol: 2013, 6(3);458-68 PMID:23413122 Fang Liu, Hans-Martin Pogoda, Caroline Alayne Pearson, Kyoji Ohyama, Heiko Löhr, Matthias Hammerschmidt, Marysia Placzek Direct and indirect roles of Fgf3 and Fgf10 in innervation and vascularisation of the vertebrate hypothalamic neurohypophysis. Development: 2013, 140(5);1111-22 PMID:23404108
- Dual ectoderm origins
- Ectoderm - ectoderm roof of stomodeum, Rathke's pouch, adenohypophysis
- Neuroectoderm - prosenecephalon then diencephalon, neurohypophysis
- Anterior wall proliferates - pars distalis
- Posterior wall little growth – pars intermedia
- Rostral growth around infundibular stem – pars tuberalis
- Infundibulum – median eminence, infundibulum, pars nervosa
Red - surface ectoderm Blue - neural tube ectoderm
|Human embryonic and fetal pituitary|
- Week 4 - hypophysial pouch, Rathke’s pouch, diverticulum from roof
- Week 5 - elongation, contacts infundibulum, diverticulum of diencephalon
- Week 6 - connecting stalk between pouch and oral cavity degenerates
- Week 10 - growth hormone and ACTH detectable
- Week 16 - adenohypophysis fully differentiated
- Week 20 to 24 - growth hormone levels peak, then decline
Embryo Week 8 Carnegie Stage 22
Developing Pituitary - Human embryo (Carnegie stage 22, week 8)
- Links: Image - Pituitary | Image - Pituitary Measured | Endocrine - Pituitary Development | Image - Low resolution Plane of Section | Image - Low resolution Pituitary
Pituitary Blood Vessel Development
|Part of pituitary||Arterial supply||Systemic venous return||Portal system return|
|Pars anterior and pars intermedia||From carotid: a bilateral supply, usually one on each side,sometimes more than one||Systemic veins to cavernous sinus following the course of the bilateral arteries||Contribute blood to portal vessels|
|Pars tuberalis||From circle of Willis by small branches around the outside of the stalk||Small systemic veins corresponding to the arteries||Contributes blood to the portal vessels|
|Pars posterior||By branches from the bilateral supply from the carotids||By small systemic venous branches following the course ofthe arterial twigs||Contributes blood to the portal vessels by fine channels opening into them below their heavy glial sleeves|
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. "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.
Hypothalamus Endocrine Axes
- Links: Image - HPA | Hypothalamus | Pituitary | Adrenal | Image - HPT Axis | Thyroid | Image - HPG female | Image - HPG male | Gonad
The hypothalamus is a small region located within the brain that controls many bodily functions, including eating and drinking, sexual functions and behaviors, blood pressure and heart rate, body temperature maintenance, the sleep-wake cycle, and emotional states (e.g., fear, pain, anger, and pleasure). Hypothalamic hormones play pivotal roles in the regulation of many of those functions. Because the hypothalamus is part of the central nervous system, the hypothalamic hormones actually are produced by nerve cells (i.e., neurons).
The anterior pituitary produces several important hormones that either stimulate target glands (e.g., the adrenal glands, gonads, or thyroid gland) to produce target gland hormones or directly affect target organs. The pituitary hormones include adreno-corticotropic hormone (ACTH); gonadotropins; thyroid-stimulating hormone (TSH), also called thyrotropin; growth hormone (GH); and prolactin.
The first three of those hormones (ACTH, gonadotropins, and TSH) act on other glands.
- ACTH stimulates the adrenal cortex to produce corticosteroid hormones (primarily cortisol) as well as small amounts of female and male sex hormones.
- Gonadotropins comprise two molecules, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These two hormones regulate the production of female and male sex hormones in the ovaries and testes as well as the production of the germ cells (oocyte and spermatozoa).
- TSH stimulates the thyroid gland to produce and release thyroid hormone.
The remaining two pituitary hormones, GH and prolactin, directly affect their target organs.
Postnatal Sexual Dimorphism
Quantitation of the human pituitary by magnetic resonance imaging (MRI) from childhood through puberty has identified volmetric differences between male and female pituitary sizes between 14 to 17 years of age.
- Females had larger pituitary glands than males in the age 14 to 17 year old groups.
- Young (19 years and under) and old (20 years and older) females demonstrated a correlation between pituitary volume and age.
- Males did not show this relationship.
- Acidophils - cytoplasm that stains red or orange (polypeptide hormones: Somatotropes, produce growth hormone; Lactotropes produce prolactin)
- Basophils - cytoplasm that stains a bluish colour (glycoprotein hormones: Thyrotropes produce thyroid stimulating hormone; Gonadotropes produce luteinizing hormone or follicle-stimulating hormone; Corticotropes produce adrenocorticotrophic hormone)
- Chromophobes - cytoplasm that stains very poorly (acidophils or basophils that are degranulated and depleted of hormone)
- Infundibular process - usually referred to as posterior pituitary (unmyelinated axons from hypothalamic neurosecretory neurons, supraoptic and paraventricular hypothalamic nuclei)
- 2 other parts: median eminence and infundibular stalk
- Pituitary development: regulatory codes in mammalian organogenesis. "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."
- Pax6 is essential for establishing ventral-dorsal cell boundaries in pituitary gland development. "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) is a transcription factor important for pituitary development and muations in this gene can lead to abnormalities in pituitary development and hormone production.
- 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
- VEGF Vascular Endothelial Growth Factor - mitogen growth factor for vascular endothelial cells. Role in pituitary vascular development. OMIM 192240 | Gene Map Locus: 1q23-q24
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)
Occurring as either a complete or partial duplication, this is an extremely rare abnormality with poor neonatal survival due to associated abnormalities.  Recently a heterozygous deletion of chromosome 14, including the thyroid transcription factor-1 gene, has been identified with duplication of the pituitary stalk.
Pituitary Adenoma Classification
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) adenoma
Growth hormone (GH) adenomas, which are benign pituitary tumors lead to chronic high GH output levels, that may lead to acromegaly in adults and gigantism in children.
Acromegaly (Greek, acro = "extremities"; megaly = "enlargement") is a clinical term for a hormonal disorder that results from excess growth hormone (GH) in the body. The pituitary produces excessive amounts of growth hormone, usually due to benign, or noncancerous, pituitary tumours (adenomas). Childhood adenomas lead to gigantism rather than acromegaly, due to continued and excess growth in the still unfused growth plates in the long bones of the legs.
- Links: NIH - acromegaly
Adrenocorticotropic (ACTH) adenoma
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). 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.
- Links: NIH - cushings
Combined Pituitary Hormone Deficiency
TBX19 and ACTH Deficiency
- ↑ Daniel Kelberman, Karine Rizzoti, Robin Lovell-Badge, Iain C A F Robinson, Mehul T Dattani Genetic regulation of pituitary gland development in human and mouse. Endocr. Rev.: 2009, 30(7);790-829 PMID:19837867 | Endocr Rev.
- ↑ Takashi Nakakura, Mayumi Yoshida, Hideo Dohra, Masakazu Suzuki, Shigeyasu Tanaka 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, 324(1);87-95 PMID:16411082
- ↑ Frank P MacMaster, Matcheri Keshavan, Yousha Mirza, Normand Carrey, Ameet R Upadhyaya, Rhonda El-Sheikh, Christian J Buhagiar, S Preeya Taormina, Courtney Boyd, Michelle Lynch, Michelle Rose, Jennifer Ivey, Gregory J Moore, David R Rosenberg Development and sexual dimorphism of the pituitary gland. Life Sci.: 2007, 80(10);940-4 PMID:17174342 | PMC1853319
- ↑ Kathleen M Scully, Michael G Rosenfeld Pituitary development: regulatory codes in mammalian organogenesis. Science: 2002, 295(5563);2231-5 PMID:11910101
- ↑ C Kioussi, S O'Connell, L St-Onge, M Treier, A S Gleiberman, P Gruss, M G Rosenfeld Pax6 is essential for establishing ventral-dorsal cell boundaries in pituitary gland development. Proc. Natl. Acad. Sci. U.S.A.: 1999, 96(25);14378-82 PMID:10588713
- ↑ S S Kollias, W S Ball, E C Prenger Review of the embryologic development of the pituitary gland and report of a case of hypophyseal duplication detected by MRI. Neuroradiology: 1995, 37(1);3-12 PMID:7708185
- ↑ S Accornero, C Danesino, S Bastianello, I D'Errico, A Guala, L Chiovato Duplication of the pituitary stalk in a patient with a heterozygous deletion of chromosome 14 harboring the thyroid transcription factor-1 gene. J. Clin. Endocrinol. Metab.: 2010, 95(8);3595-6 PMID:20685887
Endocrinology: An Integrated Approach Nussey, S.S. and Whitehead, S.A. Oxford, UK: BIOS Scientific Publishers, Ltd; 2001. table of Contents | The pituitary gland | Embryology of the pituitary gland | Blood supply of the hypothalamo-pituitary axis
NIH Genes & Disease Chapter 41 - Endocrine
Developmental Biology (6th ed) Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000.
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
Health Services/Technology Assessment Text (HSTAT) Bethesda (MD): National Library of Medicine (US), 2003 Oct. Pituitary Gland search Results
Daniel Kelberman, Karine Rizzoti, Robin Lovell-Badge, Iain C A F Robinson, Mehul T Dattani Genetic regulation of pituitary gland development in human and mouse. Endocr. Rev.: 2009, 30(7);790-829 PMID:19837867
M G Rosenfeld, P Briata, J Dasen, A S Gleiberman, C Kioussi, C Lin, S M O'Connell, A Ryan, D P Szeto, M Treier Multistep signaling and transcriptional requirements for pituitary organogenesis in vivo. Recent Prog. Horm. Res.: 2000, 55();1-13; discussion 13-4 PMID:11036930
H Z Sheng, H Westphal Early steps in pituitary organogenesis. Trends Genet.: 1999, 15(6);236-40 PMID:10354584
C Kioussi, C Carrière, M G Rosenfeld A model for the development of the hypothalamic-pituitary axis: transcribing the hypophysis. Mech. Dev.: 1999, 81(1-2);23-35 PMID:10330482
Takashi Nakakura, Mayumi Yoshida, Hideo Dohra, Masakazu Suzuki, Shigeyasu Tanaka 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, 324(1);87-95 PMID:16411082
C Kioussi, S O'Connell, L St-Onge, M Treier, A S Gleiberman, P Gruss, M G Rosenfeld Pax6 is essential for establishing ventral-dorsal cell boundaries in pituitary gland development. Proc. Natl. Acad. Sci. U.S.A.: 1999, 96(25);14378-82 PMID:10588713
M Treier, S O'Connell, A Gleiberman, J Price, D P Szeto, R Burgess, P T Chuang, A P McMahon, M G Rosenfeld Hedgehog signaling is required for pituitary gland development. Development: 2001, 128(3);377-86 PMID:11152636
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- adenohypophyseal placode - Specialised cranial surface ectoderm placode region that will form the endocrine anterior pituitary (adenohypophysis).
- adenohypophysis - (anterior pituitary, pars distalis) The anterior part of the pituitary, which develops in the early embryo from the surface ectoderm adenohypophyseal placode. This placode will fold inward on the roof of the pharynx forming a transient structure Rathke's pouch, that looses its connection with the surface.
- Rathke's pouch - An ectodermal fold in roof of pharynx forming anterior pituitary (adenohypophysis) and pars intermedia. Named after German embryologist and anatomist Martin Heinrich Rathke (1793 -1860). (More? Martin Heinrich Rathke)
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