Talk:Endocrine - Pituitary Development

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Cite this page: Hill, M.A. (2021, November 27) Embryology Endocrine - Pituitary Development. Retrieved from

10 Most Recent Papers

Note - This sub-heading shows an automated computer PubMed search using the listed sub-heading term. References appear in this list based upon the date of the actual page viewing. Therefore the list of references do not reflect any editorial selection of material based on content or relevance. In comparison, references listed on the content page and discussion page (under the publication year sub-headings) do include editorial selection based upon relevance and availability. (More? Pubmed Most Recent)

Pituitary Development

<pubmed limit=10>Pituitary Development</pubmed>

Pituitary Embryology

<pubmed limit=10>Pituitary Embryology</pubmed>


Canonical WNT Signaling Regulates the Pituitary Organizer and Pituitary Gland Formation

Endocrinology. 2017 Oct 1;158(10):3339-3353. doi: 10.1210/en.2017-00581.

Osmundsen AM1, Keisler JL1, Taketo MM2, Davis SW1.


The pituitary organizer is a domain within the ventral diencephalon that expresses Bmp4, Fgf8, and Fgf10, which induce the formation of the pituitary precursor, Rathke's pouch, from the oral ectoderm. The WNT signaling pathway regulates this pituitary organizer such that loss of Wnt5a leads to an expansion of the pituitary organizer and an enlargement of Rathke's pouch. WNT signaling is classified into canonical signaling, which is mediated by β-CATENIN, and noncanonical signaling, which operates independently of β-CATENIN. WNT5A is typically classified as a noncanonical WNT; however, other WNT family members are expressed in the ventral diencephalon and nuclear localized β-CATENIN is observed in the ventral diencephalon. Therefore, we sought to determine whether canonical WNT signaling is necessary for regulation of pituitary organizer function. Using a conditional loss-of-function approach, we deleted β-catenin within the mouse ventral diencephalon. Mutant embryos have a smaller Rathke's pouch, resulting from a reduced pituitary organizer, especially Fgf8. This result suggests that canonical WNT signaling promotes pituitary organizer function, instead of inhibiting it. To test this hypothesis, we stimulated canonical WNT signaling in the ventral diencephalon using an inducible gain-of-function allele of β-catenin and found that stimulating canonical WNT signaling expands the domain of Fgf8 and results in a dysmorphic Rathke's pouch. These results demonstrate that canonical WNT signaling in the ventral diencephalon is necessary for proper expression of pituitary organizer genes and suggests that a balance of both canonical and noncanonical WNT signaling is necessary to ensure proper formation of Rathke's pouch. Comment in Hypothalamic β-Catenin Is Essential for FGF8-Mediated Anterior Pituitary Growth: Links to Human Disease. [Endocrinology. 2017]


β-catenin is required in the neural crest and mesencephalon for pituitary gland organogenesis

BMC Dev Biol. 2016 May 16;16(1):16. doi: 10.1186/s12861-016-0118-9.

Davis SW1, Mortensen AH2, Keisler JL3, Zacharias AL4,5, Gage PJ4, Yamamura K6, Camper SA2.

Abstract BACKGROUND: The pituitary gland is a highly vascularized tissue that requires coordinated interactions between the neural ectoderm, oral ectoderm, and head mesenchyme during development for proper physiological function. The interactions between the neural ectoderm and oral ectoderm, especially the role of the pituitary organizer in shaping the pituitary precursor, Rathke's pouch, are well described. However, less is known about the role of head mesenchyme in pituitary organogenesis. The head mesenchyme is derived from definitive mesoderm and neural crest, but the relative contributions of these tissues to the mesenchyme adjacent to the pituitary are not known. RESULTS: We carried out lineage tracing experiments using two neural crest-specific mouse cre lines, Wnt1-cre and P0-cre, and determined that the head mesenchyme rostral to the pituitary gland is neural crest derived. To assess the role of the neural crest in pituitary development we ablated it, using Wnt1-cre to delete Ctnnb1 (β-catenin), which is required for neural crest development. The Wnt1-cre is active in the neural ectoderm, principally in the mesencephalon, but also in the posterior diencephalon. Loss of β-catenin in this domain causes a rostral shift in the ventral diencephalon, including the pituitary organizer, resulting in pituitary dysmorphology. The neural crest deficient embryos have abnormally dilated pituitary vasculature due to a loss of neural crest derived pericytes. CONCLUSIONS: β-catenin in the Wnt1 expression domain, including the neural crest, plays a critical role in regulation of pituitary gland growth, development, and vascularization. KEYWORDS: Neural crest; Organogenesis; Pituitary gland; Vasculature; β-catenin

PMID 27184910 PMCID: PMC4868042 DOI: 10.1186/s12861-016-0118-9


A journey through the pituitary gland: Development, structure and function, with emphasis on embryo-foetal and later development

Acta Histochem. 2015 May-Jun;117(4-5):355-66. doi: 10.1016/j.acthis.2015.02.008. Epub 2015 Apr 6.

Musumeci G1, Castorina S1, Castrogiovanni P2, Loreto C1, Leonardi R3, Aiello FC1, Magro G4, Imbesi R1.


The pituitary gland and the hypothalamus are morphologically and functionally associated in the endocrine and neuroendocrine control of other endocrine glands. They therefore play a key role in a number of regulatory feedback processes that co-ordinate the whole endocrine system. Here we review the neuroendocrine system, from the discoveries that led to its identification to some recently clarified embryological, functional, and morphological aspects. In particular we review the pituitary gland and the main notions related to its development, organization, cell differentiation, and vascularization. Given the crucial importance of the factors controlling neuroendocrine system development to understand parvocellular neuron function and the aetiology of the congenital disorders related to hypothalamic-pituitary axis dysfunction, we also provide an overview of the molecular and genetic studies that have advanced our knowledge in the field. Through the action of the hypothalamus, the pituitary gland is involved in the control of a broad range of key aspects of our lives: the review focuses on the hypothalamic-pituitary-gonadal axis, particularly GnRH, whose abnormal secretion is associated with clinical conditions involving delayed or absent puberty and reproductive dysfunction. Copyright © 2015 Elsevier GmbH. All rights reserved. KEYWORDS: Hypothalamic–pituitary axis dysfunction; Hypothalamic–pituitary–gonadal axis; Hypothalamus; Neuroendocrine system; Pituitary gland

PMID 25858531


Pituitary gland development: an update

Endocr Dev. 2012;23:1-15. doi: 10.1159/000341733. Epub 2012 Nov 23.

Bancalari RE, Gregory LC, McCabe MJ, Dattani MT. Source Developmental Endocrinology Research Group, Clinical and Molecular Genetics Unit, University College London-Institute of Child Health, London, UK.


The embryonic development of the pituitary gland involves a complex and highly spatio-temporally regulated network of integrating signalling molecules and transcription factors. Genetic mutations in any of these factors can lead to congenital hypopituitarism in association with a wide spectrum of craniofacial/midline defects ranging from incompatibility with life to holoprosencephaly (HPE) and cleft palate and septo-optic dysplasia (SOD). Increasing evidence supports a genotypic overlap with hypogonadotrophic hypogonadal disorders such as Kallmann syndrome, which is consistent with the known overlap in phenotypes between these disorders. This chapter reviews the cascade of events leading up to the successful development of the pituitary gland and to highlight key areas where genetic variations can occur thus leading to congenital hypopituitarism and associated defects. Copyright © 2012 S. Karger AG, Basel.

PMID 23182816

Follicle-Stimulating Hormone Accelerates Mouse Oocyte Development In Vivo

Biol Reprod. 2012 Apr 18. [Epub ahead of print]

Demeestere I, Streiff AK, Suzuki J, Al-Khabouri S, Mahrous E, Tan SL, Clarke HJ. Abstract During folliculogenesis, oocytes grow and acquire developmental competence in a mutually dependent relationship with their adjacent somatic cells. Follicle-stimulating hormone (FSH) plays an essential and well-established role in the differentiation of the somatic follicular cells, but its function in the development of the oocyte has still not been elucidated. We report here the oocytes of Fshb(-/-) mice, which cannot produce FSH, grow at the same rate and reach the same size as those of wild-type mice. Consistent with this observation, the granulosa cells of Fshb(-/-) mice express the normal quantity of mRNA encoding Kit ligand, which has been implicated in oocyte growth. Oocytes of Fshb(-/-) mice also accumulate normal quantities of cyclin B1 and CDK1 proteins and mitochondrial DNA. Moreover, they acquire the ability to complete meiotic maturation in vitro and undergo the transition from non-surrounded nucleolus to surrounded nucleolus. However, these events of late oocyte development are significantly delayed. Following in vitro maturation and fertilization, however, only a small number of embryos derived from oocytes of Fshb(-/-) mice reach the blastocyst stage. Administration of equine chorionic gonadotropin, which provides FSH activity, 48 h before in vitro maturation increases the number of blastocysts subsequently obtained. These results indicate that FSH is not absolutely required for oocyte development in vivo but this process occurs more rapidly in its presence. We suggest that FSH may coordinate the development of the germ-line and somatic compartments of the follicle, ensuring that ovulation releases a developmentally competent egg.

PMID 22517620

Normal pituitary stalk: high-resolution MR imaging at 3T.

AJNR Am J Neuroradiol. 2010 Feb;31(2):355-9. doi: 10.3174/ajnr.A1836. Epub 2009 Oct 1.

Satogami N, Miki Y, Koyama T, Kataoka M, Togashi K. Source Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.


BACKGROUND AND PURPOSE: Knowing the normal imaging appearance of the pituitary stalk is important for the diagnosis of pituitary infundibular lesions, and more accurate assessment of the stalk may be possible at 3T than at 1.5T. Our purpose was to evaluate the normal pituitary stalk by use of high-resolution MR imaging at 3T. MATERIALS AND METHODS: Sagittal MPRAGE images and high-resolution oblique-axial T2-weighted images of the pituitary stalk were acquired in 29 healthy volunteers (16 men and 13 women; mean age, 28 years; age range, 21-43 years) at 3T. The diameter and length of the pituitary stalk and the depth of the infundibular recess were measured. Signal intensity of the stalk was visually evaluated on T2-weighted images. RESULTS: The AP and transverse diameters of the pituitary stalk were 2.32 +/- 0.39 mm and 2.16 +/- 0.37 mm at the pituitary insertion, respectively, and 3.25 +/- 0.43 mm and 3.35 +/- 0.44 mm at the level of the optic chiasm. No significant differences were observed between the AP and transverse diameters at each level. The length of the stalk was 5.91 +/- 1.24 mm, and the depth of the infundibular recess was 4.69 +/- 0.87 mm. The stalk showed central hyperintensity with a peripheral rim of isointensity in 20 subjects (69%) and homogeneous isointensity in 9 subjects (31%). CONCLUSIONS: The data of the current study can serve as standard measurements of the normal pituitary stalk. The central hyperintensity and peripheral rim may represent the infundibular stem and pars tuberalis, respectively.

PMID 19797792


Identification of candidate genes for human pituitary development by EST analysis

Ma Y, Qi X, Du J, Song S, Feng D, Qi J, Zhu Z, Zhang X, Xiao H, Han Z, Hao X. BMC Genomics. 2009 Mar 15;10:109.

BACKGROUND: The pituitary is a critical neuroendocrine gland that is comprised of five hormone-secreting cell types, which develops in tandem during the embryonic stage. Some essential genes have been identified in the early stage of adenohypophysial development, such as PITX1, FGF8, BMP4 and SF-1. However, it is likely that a large number of signaling molecules and transcription factors essential for determination and terminal differentiation of specific cell types remain unidentified. High-throughput methods such as microarray analysis may facilitate the measurement of gene transcriptional levels, while Expressed sequence tag (EST) sequencing, an efficient method for gene discovery and expression level analysis, may no-redundantly help to understand gene expression patterns during development.

RESULTS: A total of 9,271 ESTs were generated from both fetal and adult pituitaries, and assigned into 961 gene/EST clusters in fetal and 2,747 in adult pituitary by homology analysis. The transcription maps derived from these data indicated that developmentally relevant genes, such as Sox4, ST13 and ZNF185, were dominant in the cDNA library of fetal pituitary, while hormones and hormone-associated genes, such as GH1, GH2, POMC, LHbeta, CHGA and CHGB, were dominant in adult pituitary. Furthermore, by using RT-PCR and in situ hybridization, Sox4 was found to be one of the main transcription factors expressed in fetal pituitary for the first time. It was expressed at least at E12.5, but decreased after E17.5. In addition, 40 novel ESTs were identified specifically in this tissue.

CONCLUSION: The significant changes in gene expression in both tissues suggest a distinct and dynamic switch between embryonic and adult pituitaries. All these data along with Sox4 should be confirmed to further understand the community of multiple signaling pathways that act as a cooperative network that regulates maturation of the pituitary. It was also suggested that EST sequencing is an efficient means of gene discovery.

PMID: 19284880

Evaluation of the Hypothalamic-Pituitary-Adrenal Axis Function in Childhood and Adolescence

Hypophyseal triplication: case report and embryologic considerations

AJNR Am J Neuroradiol. 2009 Aug;30(7):1328-9. Epub 2009 Mar 19.

Manara R, Citton V, Rossetto M, Padoan A, D'Avella D.

Neuroradiologic Unit, University Hospital of Padua, Padua, Italy. Abstract SUMMARY: Hypophyseal triplication is malformation that has not been described previously. We present a child with midline abnormalities who underwent epignathus excision at birth. Brain MR imaging revealed 2 paired lateral pituitary glands and an oval midline gland, each with an independent stalk, connected to a thickened third ventricle floor. Because malformations represent a failure in embryogenesis, this case may provide interesting clues on the normal development of the hypophysis.

PMID: 19299490

Theory comparison

  • According to the classic theory,1,3,5 the hypophysis is believed to arise from 2 distinct structures, namely the diencephalic neuroectoderm (posterior lobe) and the oral ectoderm (anterior lobe). At approximately 42 days of gestation, a diverticulum originating from the stomodeum fuses with the downward extending diencephalic bud, both finally housed in the pituitary fossa.
  • In contrast to the traditional view, Gilbert (1934) found that in mammalian species, both the anterior and posterior part of the gland originate from the ventral neural ridge.1 In this model, resumed by Morton in 19574 in a case report of pituitary duplication, the gland is supposed to arise entirely from neuroectodermal tis- sue without the primary involvement of the Rathke pouch.

Prenatal MR imaging of the normal pituitary stalk

AJNR Am J Neuroradiol. 2009 May;30(5):1014-6. Epub 2009 Feb 4.

Righini A, Parazzini C, Doneda C, Arrigoni F, Triulzi F.

Radiology and Neuroradiology Department, Children's Hospital V. Buzzi, ICP, Milan, Italy. Abstract BACKGROUND AND PURPOSE: Prenatal imaging data of the normal pituitary gland and in vivo information on the development of the pituitary region are lacking; however, we noticed that the pituitary stalk (PS) is visible occasionally in utero on MR images. Our main purpose was to establish the detection rate of the PS in healthy fetuses at various gestational ages (GAs) by using single-shot fast spin-echo T2-weighted images.

MATERIALS AND METHODS: We selected 73 fetal cases with normal findings on prenatal MR imaging and clinical postnatal follow-up. The GA ranged between 19 and 37 weeks. The 3 planes of MR imaging sections were 4 mm thick with 1.25 x 1.25 mm in-plane resolution. Two pediatric neuroradiologists evaluated in consensus whether the PS was present as a linear isointense structure connecting the hypothalamic region with the floor of sella turcica. In those cases in which the PS was visible on the sagittal section, the angle formed by the intersection of the PS and the sellar plane (SP) was measured (PS-SP angle).

RESULTS: The PS was detectable on at least 1 coronal or sagittal section from 19 to 25 weeks' GA in 30/42 fetuses (71.4% sensitivity); from 26 to 37 weeks' GA, the PS was detected in all 31 fetuses (100% sensitivity). The PS-SP angle decreased significantly with GA, being <90 degrees in all fetuses after gestational week 25.

CONCLUSIONS: At the current spatial resolution of clinical prenatal MR imaging, PS can be reliably detected after 25 weeks' GA, so in case of a missing visualization, a strong suspicion of pituitary region anomaly could be raised.

PMID: 19193754


Development and sexual dimorphism of the pituitary gland

Life Sci. 2007 Feb 13;80(10):940-4. Epub 2006 Nov 29.

MacMaster FP, Keshavan M, Mirza Y, Carrey N, Upadhyaya AR, El-Sheikh R, Buhagiar CJ, Taormina SP, Boyd C, Lynch M, Rose M, Ivey J, Moore GJ, Rosenberg DR.

Department of Psychiatry & Behavioral Neurosciences, Wayne State University, and Children's Hospital of Michigan, Detroit, MI 48201, USA. Abstract The pituitary gland plays a central role in sexual development and brain function. Therefore, we examined the effect of age and gender on pituitary volume in a large sample of healthy children and adults. Volumetric magnetic resonance imaging (MRI) was conducted in one hundred and fifty four (77 males and 77 females) healthy participants. Males were between the ages of 7 to 35 years (16.91+/-5.89 years) and females were 7 to 35 years of age (16.75+/-5.75 years). Subjects were divided into subgroups of age (7 to 9, 10 to 13, 14 to 17, 18 to 21, 22 and older) and sex (male/female). Pituitary gland volume differed between sexes when comparing the age groups (F=3.55, df=2, 143, p=0.03). Females demonstrated larger pituitary glands than males in the age 14 to 17 year old groups (p=0.04). 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. These findings provide additional evidence for gender differences in the normative anatomy of the pituitary and may have relevance for the study of various childhood onset neuropsychiatric disorders in which pituitary dysfunction has been implicated.

PMID: 17174342