Talk:Endocrine - Hypothalamus Development
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Cite this page: Hill, M.A. (2024, April 16) Embryology Endocrine - Hypothalamus Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Endocrine_-_Hypothalamus_Development |
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)
Hypothalamus Embryology
<pubmed limit=5>Thyroid Embryology</pubmed>
Hypothalamus Development
<pubmed limit=5>Thyroid Development</pubmed>
Acronyms
- 3ß-diol - 5alpha-androstane-3beta, 17beta-diol
- 3α-diol - 5alpha-androstane-3alpha, 17beta-diol
- 5-HT - serotonin
- 5αR - 5-alpha-reductase
- ACTH - adrenocortcotropin releasing hormone
- AR - androgen receptor
- AVP - arginine vasopressin
- BnST - bed nucleus of the stria terminalis
- BSA - bovine serum albumin
- CBP - CREB binding protein
- CORT - corticosterone
- CRE - cyclic adenosine monophosphate response element
- CREB - CRE binding protein
- CRF - corticotropin releasing factor
- DES - diethylstilbesterol
- DEX - dexamethasone
- DHT - dihydrotestosterone
- DPN - diarylproprionitrile
- ER - estrogen receptor
- ERE - estrogen response element
- FSH - follicle stimulating hormone
- FSL - flinders sensitive line
- GABA - gamma-aminobutyric acid
- GAS - general adaptation syndrome
- GH - growth hormone
- GLP-1 - glucagon-like peptide 1
- GnRH - gonadotropin releasing hormone
- GPER - G-protein coupled estrogen receptor
- GR - glucocorticoid receptor
- HPA - hypothalamo–pituitary–adrenal
- HPG - hypothalamo–pituitary–gonadal
- HRE - hormone respone element
- HSD - hydroxysteroid dehydrogenase
- ICV - intracerebroventricular
- ir - immunoreactive
- ISH - in situ hybridization
- LH - luteinizing hormone
- LHRH - luteinizing hormone releasing hormone
- MPOA - medial preoptic area
- MR - mineralocorticoid receptor
- NTS - nucleus of the solitary tract
- PPT - propylpyrazoletriol
- PR - progesterone receptor
- PVN - paraventricular nucleus
- RAR - retinoic acid receptors
- SCN - suprachiasmatic nucleus
- SRC - steroid receptor coactivators
- T - testosterone
- THR - thyroid hormone receptors
- TPH - tryptophan hydroxylase
- TRH - thyrotropin releasing hormone
- TSH - thyroid stimulating hormone
2014
Development of the HPA axis: Where and when do sex differences manifest?
Front Neuroendocrinol. 2014 Mar 13. pii: S0091-3022(14)00036-3. doi: 10.1016/j.yfrne.2014.03.002. [Epub ahead of print]
Panagiotakopoulos L1, Neigh GN2.
Abstract
Sex differences in the response to stress contribute to sex differences in somatic, neurological, and psychiatric diseases. Despite a growing literature on the mechanisms that mediate sex differences in the stress response, the ontogeny of these differences has not been comprehensively reviewed. This review focuses on the development of the hypothalamic-pituitary-adrenal (HPA) axis, a key component of the body's response to stress, and examines the critical points of divergence during development between males and females. Insight gained from animal models and clinical studies are presented to fully illustrate the current state of knowledge regarding sex differences in response to stress over development. An appreciation for the developmental timelines of the components of the HPA axis will provide a foundation for future areas of study by highlighting both what is known and calling attention to areas in which sex differences in the development of the HPA axis have been understudied. Copyright © 2014 Elsevier Inc. All rights reserved. KEYWORDS: Adrenals, CRF, Development, Glucocorticoids, HPA axis, Hippocampus, Hormones, Hypothalamus, Pituitary, Sex
PMID 24631756
Development of the blood-brain barrier within the paraventricular nucleus of the hypothalamus: influence of fetal glucocorticoid excess
Brain Struct Funct. 2014 May 11. [Epub ahead of print]
Frahm KA1, Tobet SA.
Abstract
The blood-brain barrier (BBB) is a critical contributor to brain function. To understand its development and potential function in different brain regions, the postnatal (P) BBB was investigated in the mouse cortex (CTX), lateral hypothalamus, and paraventricular nucleus of the hypothalamus (PVN). Brains were examined on postnatal days (P)12, P22 and P52 for BBB competency and for pericytes as key cellular components of the BBB demarcated by immunoreactive desmin. Glucocorticoid influences (excess dexamethasone; dex) during prenatal development were also assessed for their impact on the blood vessels within these regions postnatally. At P12, there was significantly more extravascular leakage of a low molecular weight dye (fluorescein isothiocyanate) in the CTX than within hypothalamic regions. For pericytes, there were low levels of desmin immunoreactivity at P12 that increased with age for all regions. There was more desmin immunoreactivity present in the PVN at each age examined. Fetal dex exposure resulted in decreased blood vessel density within the PVN at P20. In the CTX, dex exposure increased BBB competency, in contrast to the PVN where there was a decrease in BBB competency and increased pericyte presence. Overall, unique alterations in the functioning of the BBB within the PVN may provide a novel mechanism for fetal antecedent programming that may influence adult disorders.
PMID 24817635
2013
Maps of the adult human hypothalamus
Surg Neurol Int. 2013 Apr 17;4(Suppl 3):S156-63. doi: 10.4103/2152-7806.110667. Print 2013.
Lemaire JJ, Nezzar H, Sakka L, Boirie Y, Fontaine D, Coste A, Coll G, Sontheimer A, Sarret C, Gabrillargues J, De Salles A. Source Univ Clermont 1, UFR Médecine, EA 7282, Image-Guided Clinical Neuroscience and Connectomics, Clermont-Ferrand, F-63001, France ; Service de Neurochirurgie, CHU Clermont-Ferrand, Clermont-Ferrand, F-63003, France. Abstract The human hypothalamus is a small deeply located region placed at the crossroad of neurovegetative, neuroendocrine, limbic, and optic systems. Although deep brain stimulation techniques have proven that it could be feasible to modulate these systems, targeting the hypothalamus and in particular specific nuclei and white bundles, is still challenging. Our goal was to make a synthesis of relevant topographical data of the human hypothalamus, under the form of magnetic resonance imaging maps useful for mastering its elaborated structure as well as its neighborhood. As from 1.5 Tesla, Inversion-Recovery sequence allows locating the hypothalamus and most of its components. Spotting hypothalamic compartments is possible according to specific landmarks: the anterior commissure, the mammillary bodies, the preoptic recess, the infundibular recess, the crest between the preoptic and the infundibular recesses, the optical tract, the fornix, and the mammillo-thalamic bundle. The identification of hypothalamus and most of its components could be useful to allow the quantification of local pathological processes and to target specific circuitry to alleviate severe symptoms, using physical or biological agents. KEYWORDS: Brain mapping, hypothalamus, inversion-recovery sequence, magnetic resonance imaging, stereotaxy
PMID 23682342
2012
MRI atlas of the human hypothalamus
Neuroimage. 2012 Jan 2;59(1):168-80. doi: 10.1016/j.neuroimage.2011.07.013. Epub 2011 Jul 14.
Baroncini M, Jissendi P, Balland E, Besson P, Pruvo JP, Francke JP, Dewailly D, Blond S, Prevot V. Source Inserm, Jean-Pierre Aubert Research Center, U837, Development and Plasticity of the postnatal Brain, Univ Lille Nord de France, CHRU Lille, Department of Neurosurgery, Lille University Hospital, 59037 Lille cedex, France. marc.baroncini@inserm.fr Abstract Gaining new insights into the anatomy of the human hypothalamus is crucial for the development of new treatment strategies involving functional stereotactic neurosurgery. Here, using anatomical comparisons between histology and magnetic resonance images of the human hypothalamus in the coronal plane, we show that discrete gray and white hypothalamic structures are consistently identifiable by MRI. Macroscopic and microscopic images were used to precisely annotate the MRI sequences realized in the coronal plane in twenty healthy volunteers. MRI was performed on a 1.5 T scanner, using a protocol including T1-weighted 3D fast field echo, T1-weighted inversion-recovery, turbo spin echo and T2-weighted 2D fast field echo imaging. For each gray matter structure as well as for white matter bundles, the different MRI sequences were analyzed in comparison to each other. The anterior commissure and the fornix were often identifiable, while the mammillothalamic tract was more difficult to spot. Qualitative analyses showed that MRI could also highlight finer structures such as the paraventricular nucleus, the ventromedial nucleus of the hypothalamus and the infundibular (arcuate) nucleus, brain nuclei that play key roles in the regulation of food intake and energy homeostasis. The posterior hypothalamic area, a target for deep brain stimulation in the treatment of cluster headaches, was readily identified, as was the lateral hypothalamic area, which similar to the aforementioned hypothalamic nuclei, could be a putative target for deep brain stimulation in the treatment of obesity. Finally, each of the identified structures was mapped to Montreal Neurological Institute (MNI) space. Copyright © 2011 Elsevier Inc. All rights reserved.
PMID 21777680
Sonic hedgehog lineage in the mouse hypothalamus: from progenitor domains to hypothalamic regions
Neural Dev. 2012 Jan 20;7:4. doi: 10.1186/1749-8104-7-4.
Alvarez-Bolado G, Paul FA, Blaess S. Source Department of Neuroanatomy, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany. alvarez@ana.uni-heidelberg.de
Abstract
BACKGROUND: The hypothalamus is a brain region with essential functions for homeostasis and energy metabolism, and alterations of its development can contribute to pathological conditions in the adult, like hypertension, diabetes or obesity. However, due to the anatomical complexity of the hypothalamus, its development is not well understood. Sonic hedgehog (Shh) is a key developmental regulator gene expressed in a dynamic pattern in hypothalamic progenitor cells. To obtain insight into hypothalamic organization, we used genetic inducible fate mapping (GIFM) to map the lineages derived from Shh-expressing progenitor domains onto the four rostrocaudally arranged hypothalamic regions: preoptic, anterior, tuberal and mammillary. RESULTS: Shh-expressing progenitors labeled at an early stage (before embryonic day (E)9.5) contribute neurons and astrocytes to a large caudal area including the mammillary and posterior tuberal regions as well as tanycytes (specialized median eminence glia). Progenitors labeled at later stages (after E9.5) give rise to neurons and astrocytes of the entire tuberal region and in particular the ventromedial nucleus, but not to cells in the mammillary region and median eminence. At this stage, an additional Shh-expressing domain appears in the preoptic area and contributes mostly astrocytes to the hypothalamus. Shh-expressing progenitors do not contribute to the anterior region at any stage. Finally, we show a gradual shift from neurogenesis to gliogenesis, so that progenitors expressing Shh after E12.5 generate almost exclusively hypothalamic astrocytes. CONCLUSIONS: We define a fate map of the hypothalamus, based on the dynamic expression of Shh in the hypothalamic progenitor zones. We provide evidence that the large neurogenic Shh-expressing progenitor domains of the ventral diencephalon are continuous with those of the midbrain. We demonstrate that the four classical transverse zones of the hypothalamus have clearly defined progenitor domains and that there is little or no cell mixing between the tuberal and anterior or the preoptic and anterior hypothalamus. Finally, we show that, in the tuberal hypothalamus, neurons destined for every mediolateral level are produced during a period of days, in conflict with the current 'three-wave' model of hypothalamic neurogenesis. Our work sets the stage for a deeper developmental analysis of this complex and important brain region.
PMID 22264356
2011
Development of Posterior Hypothalamic Neurons Enlightens a Switch in the Prosencephalic Basic Plan
In rats and mice, ascending and descending axons from neurons producing melanin-concentrating hormone (MCH) reach the cerebral cortex and spinal cord. However, these ascending and descending projections originate from distinct sub-populations expressing or not “Cocaine-and-Amphetamine-Regulated-Transcript”(CART) peptide. Using a BrdU approach, MCH cell bodies are among the very first generated in the hypothalamus, within a longitudinal cell cord made of earliest delaminating neuroblasts in the diencephalon and extending from the chiasmatic region to the ventral midbrain. This region also specifically expresses the regulatory genes Sonic hedgehog (Shh) and Nkx2.2.
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0028574
The Krüppel-like factor 4 controls biosynthesis of thyrotropin-releasing hormone during hypothalamus development
Mol Cell Endocrinol. 2011 Feb 20;333(2):127-33. Epub 2010 Dec 21.
Pérez-Monter C, Martínez-Armenta M, Miquelajauregui A, Furlan-Magaril M, Varela-Echavarría A, Recillas-Targa F, May V, Charli JL, Pérez-Martínez L. Source Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62271, Mexico.
Abstract
Embryonic neurogenesis is controlled by the activation of specific genetic programs. In the hypothalamus, neuronal thyrotropin-releasing hormone (TRH) populations control important physiological process, including energy homeostasis and autonomic function; however, the genetic program leading to the TRH expression is poorly understood. Here, we show that the Klf4 gene, encoding the transcription factor Krüppel-like factor 4 (Klf4), was expressed in the rat hypothalamus during development and regulated Trh expression. In rat fetal hypothalamic cells Klf4 regulated Trh promoter activity through CACCC and GC motifs present on the Trh gene promoter. Accordingly, hypothalamic Trh expression was down-regulated at embryonic day 15 in the Klf4(-/-) mice resulting in diminished bioactive peptide levels. Although at the neonatal stage the Trh transcript levels of the Klf4(-/-) mice were normal, the reduction in peptide levels persisted. Thus, our data indicate that Klf4 plays a key role in the maturation of TRH expression in hypothalamic neurons. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
PMID 21182892
Prenatal PCBs disrupt early neuroendocrine development of the rat hypothalamus
Toxicol Appl Pharmacol. 2011 Apr 1;252(1):36-46. Epub 2011 Jan 26.
Dickerson SM, Cunningham SL, Gore AC. Source Center for Molecular and Cellular Toxicology, Division of Pharmacology and Toxicology, University of Texas at Austin, Austin, TX 78712, USA.
Abstract
Neonatal exposure to endocrine disrupting chemicals (EDCs) such as polychlorinated biphenyls (PCBs) can interfere with hormone-sensitive developmental processes, including brain sexual differentiation. We hypothesized that disruption of these processes by gestational PCB exposure would be detectable as early as the day after birth (postnatal day (P) 1) through alterations in hypothalamic gene and protein expression. Pregnant Sprague-Dawley rats were injected twice, once each on gestational days 16 and 18, with one of the following: DMSO vehicle; the industrial PCB mixture Aroclor 1221 (A1221); a reconstituted mixture of the three most prevalent congeners found in humans, PCB138, PCB153, and PCB180; or estradiol benzoate (EB). On P1, litter composition, anogenital distance (AGD), and body weight were assessed. Pups were euthanized for immunohistochemistry of estrogen receptor α (ERα) or TUNEL labeling of apoptotic cells or quantitative PCR of 48 selected genes in the preoptic area (POA). We found that treatment with EB or A1221 had a sex-specific effect on developmental apoptosis in the neonatal anteroventral periventricular nucleus (AVPV), a sexually dimorphic hypothalamic region involved in the regulation of reproductive neuroendocrine function. In this region, exposed females had increased numbers of apoptotic nuclei, whereas there was no effect of treatment in males. For ERα, EB treatment increased immunoreactive cell numbers and density in the medial preoptic nucleus (MPN) of both males and females, while A1221 and the PCB mixture had no effect. PCR analysis of gene expression in the POA identified nine genes that were significantly altered by prenatal EDC exposure, in a manner that varied by sex and treatment. These genes included brain-derived neurotrophic factor, GABA(B) receptors-1 and -2, IGF-1, kisspeptin receptor, NMDA receptor subunits NR2b and NR2c, prodynorphin, and TGFα. Collectively, these results suggest that the disrupted sexual differentiation of the POA by prenatal EDC exposures is already evident as early as the day after birth, effects that may change the trajectory of postnatal development and compromise adult reproductive function.
Copyright © 2011 Elsevier Inc. All rights reserved.
PMID 21277884
Neuropeptide Signaling Differentially Affects Phase Maintenance and Rhythm Generation in SCN and Extra-SCN Circadian Oscillators
PLoS One. 2011 Apr 29;6(4):e18926.
Hughes AT, Guilding C, Piggins HD. Source Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
Abstract
Circadian rhythms in physiology and behavior are coordinated by the brain's dominant circadian pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus. Vasoactive intestinal polypeptide (VIP) and its receptor, VPAC(2), play important roles in the functioning of the SCN pacemaker. Mice lacking VPAC(2) receptors (Vipr2(-/-)) express disrupted behavioral and metabolic rhythms and show altered SCN neuronal activity and clock gene expression. Within the brain, the SCN is not the only site containing endogenous circadian oscillators, nor is it the only site of VPAC(2) receptor expression; both VPAC(2) receptors and rhythmic clock gene/protein expression have been noted in the arcuate (Arc) and dorsomedial (DMH) nuclei of the mediobasal hypothalamus, and in the pituitary gland. The functional role of VPAC(2) receptors in rhythm generation and maintenance in these tissues is, however, unknown. We used wild type (WT) and Vipr2(-/-) mice expressing a luciferase reporter (PER2::LUC) to investigate whether circadian rhythms in the clock gene protein PER2 in these extra-SCN tissues were compromised by the absence of the VPAC(2) receptor. Vipr2(-/-) SCN cultures expressed significantly lower amplitude PER2::LUC oscillations than WT SCN. Surprisingly, in Vipr2(-/-) Arc/ME/PT complex (Arc, median eminence and pars tuberalis), DMH and pituitary, the period, amplitude and rate of damping of rhythms were not significantly different to WT. Intriguingly, while we found WT SCN and Arc/ME/PT tissues to maintain a consistent circadian phase when cultured, the phase of corresponding Vipr2(-/-) cultures was reset by cull/culture procedure. These data demonstrate that while the main rhythm parameters of extra-SCN circadian oscillations are maintained in Vipr2(-/-) mice, the ability of these oscillators to resist phase shifts is compromised. These deficiencies may contribute towards the aberrant behavior and metabolism associated with Vipr2(-/-) animals. Further, our data indicate a link between circadian rhythm strength and the ability of tissues to resist circadian phase resetting.
PMID 21559484
Perinatal photoperiod imprints the circadian clock
Christopher M Ciarleglio, John C Axley, Benjamin R Strauss, Karen L Gamble and Douglas G McMahon doi:10.1038/nn.2699
This study finds that mice's biological clocks are permanently influenced by the seasonal photoperiod at and after birth. In mice raised under summer-like light periods, rhythmic gene expression in the suprachiasmatic nucleus was tightly correlated with lights-off under both summer- and winter-like cycles. In 'winter-born' mice, these rhythms were tightly correlated only under winter-like light cycles.
Nature Neuroscience 14, 25–27 (2011) doi:10.1038/nn.2699 Received 24 August 2010 Accepted 21 October 2010 Published online 05 December 2010 http://www.nature.com/neuro/journal/v14/n1/abs/nn.2699.html?lang=en
2010
Oxytocin-Gly-Lys-Arg: a novel cardiomyogenic peptide
PLoS One. 2010 Oct 26;5(10):e13643.
Danalache BA, Gutkowska J, Slusarz MJ, Berezowska I, Jankowski M.
Research Centre, Centre Hospitalier de l'Université de Montréal - Hôtel-Dieu, Montreal, Quebec, Canada. Abstract BACKGROUND: Oxytocin (OT), synthesized in the heart, has the ability to heal injured hearts and to promote cardiomyogenesis from stem cells. Recently, we reported that the OT-GKR molecule, a processing intermediate of OT, potently increased the spontaneous formation of cardiomyocytes (CM) in embryonic stem D3 cells and augmented glucose uptake in newborn rat CM above the level stimulated by OT. In the present experiments, we investigated whether OT-GKR exists in fetal and newborn rodent hearts, interacts with the OT receptors (OTR) and primes the generation of contracting cells expressing CM markers in P19 cells, a model for the study of early heart differentiation.
METHODOLOGY/PRINCIPAL FINDINGS: High performance liquid chromatography of newborn rat heart extracts indicated that OT-GKR was a dominant form of OT. Immunocytochemistry of mouse embryos (embryonic day 15) showed cardiac OT-GKR accumulation and OTR expression. Computerized molecular modeling revealed OT-GKR docking to active OTR sites and to V1a receptor of vasopressin. In embryonic P19 cells, OT-GKR induced contracting cell colonies and ventricular CM markers more potently than OT, an effect being suppressed by OT antagonists and OTR-specific small interfering (si) RNA. The V1a receptor antagonist and specific si-RNA also significantly reduced OT-GKR-stimulated P19 contracting cells. In comparison to OT, OT-GKR induced in P19 cells less α-actinin, myogenin and MyoD mRNA, skeletal muscle markers.
CONCLUSIONS/SIGNIFICANCE: These results raise the possibility that C-terminally extended OT molecules stimulate CM differentiation and contribute to heart growth during fetal life.
PMID: 21048978
Interactions of the Circadian CLOCK System and the HPA Axis
Trends Endocrinol Metab. 2010 May;21(5):277-86. Epub 2010 Jan 26.
Nader N, Chrousos GP, Kino T.
Unit on Molecular Hormone Action, Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Abstract Organisms have developed concurrent behavioral and physiological adaptations to the strong influence of day/night cycles, as well as to unforeseen, random stress stimuli. These circadian and stress-related responses are achieved by two highly conserved and interrelated regulatory networks, the circadian CLOCK and stress systems, which respectively consist of oscillating molecular pacemakers, the Clock/Bmal1 transcription factors, and the hypothalamic-pituitary-adrenal (HPA) axis and its end-effector, the glucocorticoid receptor. These systems communicate with one another at different signaling levels and dysregulation of either system can lead to development of pathologic conditions. In this review, we summarize the mutual physiologic interactions between the circadian CLOCK system and the HPA axis, and discuss their clinical implications.
PMID: 20106676 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862789/?tool=pubmed
2009
Vertebrate retina and hypothalamus development
Wiley Interdiscip Rev Syst Biol Med. 2009 Nov-Dec;1(3):380-9.
Byerly MS, Blackshaw S. Source Department of Neuroscience, Neurology and Ophthalamology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Abstract
The vertebrate retina and hypothalamus, which emerge from adjacent regions of the ventral diencephalon, provide accessible experimental systems for analysis of the molecular mechanisms by which neuronal subtype diversity is specified, and how this neuronal subtype diversity regulates perception and behavior. Although the retina emerges as a lateral extension of the hypothalamus prior to the onset of neurogenesis, the retina and hypothalamus go on to eventually be comprised of almost entirely different cell types, and differ extensively in the spatial organization, function, and connectivity of these cells. Despite these differences in cell composition, there are a number of mechanistic and molecular similarities in the process of cell fate specification in both organs, including a stereotyped temporal sequence in which major cell types are generated. Although a handful of genes have been identified in both systems that direct cell fate specification, many more remain to be characterized, and large numbers of candidate genes have been identified in recent high-throughput screens, particularly in retina. Experimental challenges for the near future include functional analysis of the genes identified so far, and the use of the molecular pathways gained from analysis of the development of specific neuronal lineages to study the contribution of these cells to perception and behavior.
PMID 20836003
Genetic regulation of pituitary gland development in human and mouse
Endocr Rev. 2009 Dec;30(7):790-829. Epub 2009 Oct 16.
Kelberman D, Rizzoti K, Lovell-Badge R, Robinson IC, Dattani MT.
Developmental Endocrinology Research Group, Clinical and Molecular Genetics Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom. Abstract Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke's pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans.
PMID 19837867
2004
Oxytocin in cardiac ontogeny
Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):13074-9. Epub 2004 Aug 17.
Jankowski M, Danalache B, Wang D, Bhat P, Hajjar F, Marcinkiewicz M, Paquin J, McCann SM, Gutkowska J.
Centre de Recherche, Centre Hospitalier de l'Université de Montréal, Hôtel-Dieu, 3840 Rue Saint-Urbain, Montréal, QC, Canada H2W 1T8. Abstract Previous studies demonstrated the presence of oxytocin (OT) and oxytocin receptors (OTRs) in the heart. The present work provides results supporting a potential role of OT in cardiomyogenesis. Here, we show a maximal OT and OTR protein level in the developing rat heart at day 21 of gestation and postnatal days 1-4, when cardiac myocytes are at a stage of intense hyperplasia. Between postnatal days 1 and 66, OT decreased linearly in all heart chambers (4.1- to 6.6-fold). Correspondingly, immunocytochemistry demonstrated that OTRs, which were eminent in postnatal cardiomyocytes, declined with age to low levels in adults. Interestingly, in coronary vasculature, OTRs developed in endothelial cells at postnatal days 12 and 22 and achieved a plateau in adult rats. These findings suggest that OT can be involved in developmental formation of the coronary vessels. In vivo, the OT/OTR system in the fetal heart was sensitive to the actions of retinoic acid (RA), recognized as a major cardiac morphogen. RA treatment produced a significant increase (2- to 3-fold) both in the OT concentration and in the OT mRNA levels. Ex vivo, an OT antagonist inhibited RA-mediated cardiomyocyte differentiation of P19 embryonic stem cells. The decline of cardiac OT expression from infancy to adulthood of the rat and changes in cell types expressing OTR indicate a dynamic regulation of the OT system in the heart rather than constitutive expression. The results support the hypothesis that RA induces cardiomyogenesis by activation of the cardiac OT system.
Copyright 2004 The National Academy of Sciencs of the USA PMID: 15316117
1990's
Oxytocin and vasopressin receptors in human and uterine myomas during menstrual cycle and early pregnancy
Hum Reprod Update. 1998 Sep-Oct;4(5):594-604.
Fuchs AR, Behrens O, Maschek H, Kupsch E, Einspanier A.
Department of Obstetrics and Gynecology, Cornell University Medical College, New York, NY 10021, USA. annariitta@aol.com Abstract The purpose of this study was to determine the specificity and concentration of oxytocin (OT) and arginine vasopressin (AVP) binding sites in non-pregnant (NP) human and rhesus monkey endometrium, myometrium and fibromyomas, and to determine the cellular localization of OT receptor (OTR). Besides [3H]AVP, [125I]LVA, a specific VP1 receptor subtype antagonist, was used to determine vasopressin receptor (VPR) concentrations. Samples were obtained from 42 pre-menopausal and three pregnant women (5, 13 and 35 weeks gestation), and several NP and pregnant monkeys. Specificity of binding was assessed in competition experiments with unlabelled agonists and antagonists of known pharmacological potency. Cellular localization of OTR was determined by immunohistochemistry. In NP human uterine tissues, [3H]AVP was bound with higher affinity and greater binding capacity than [3H]OT, whereas in pregnant women and in NP and pregnant rhesus monkeys, uterine OT binding capacity was greater. OT and AVP binding sites discriminated very poorly between OT and AVP; [125I]LVA binding sites were more selective than [3H]AVP. Their ligand specificity and binding kinetics indicated the presence of two distinct populations of binding sites for OT and AVP in primate uterus. Endometrium of NP women and monkeys had low OTR and VPR concentrations. Myometrial and endometrial OTR and VPR were down-regulated in midcycle and in early human pregnancy, they were up-regulated in the secretory phase and second half of pregnancy. Immunoreactive OTR in NP uterus was localized in patches of myometrial muscle cells and small numbers of endometrial epithelial cells.
PMID: 10027613
