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Cellular and Molecular Life Sciences :... Dec 2022Stem cells in the anterior pituitary gland can give rise to all resident endocrine cells and are integral components for the appropriate development and subsequent... (Review)
Review
Stem cells in the anterior pituitary gland can give rise to all resident endocrine cells and are integral components for the appropriate development and subsequent maintenance of the organ. Located in discreet niches within the gland, stem cells are involved in bi-directional signalling with their surrounding neighbours, interactions which underpin pituitary gland homeostasis and response to organ challenge or physiological demand. In this review we highlight core signalling pathways that steer pituitary progenitors towards specific endocrine fate decisions throughout development. We further elaborate on those which are conserved in the stem cell niche postnatally, including WNT, YAP/TAZ and Notch signalling. Furthermore, we have collated a directory of single cell RNA sequencing studies carried out on pituitaries across multiple organisms, which have the potential to provide a vast database to study stem cell niche components in an unbiased manner. Reviewing published data, we highlight that stem cells are one of the main signalling hubs within the anterior pituitary. In future, coupling single cell sequencing approaches with genetic manipulation tools in vivo, will enable elucidation of how previously understudied signalling pathways function within the anterior pituitary stem cell niche.
Topics: Humans; Stem Cell Niche; Pituitary Diseases; Pituitary Gland; Cell Communication; Signal Transduction
PubMed: 36451046
DOI: 10.1007/s00018-022-04612-8 -
Functional Restoration of Pituitary after Pituitary Allotransplantation into Hypophysectomized Rats.Cells Jan 2021Long-term hormone replacement therapy due to panhypopituitarism can lead to serious complications and thus, pituitary transplantation is considered a more desirable. We...
Long-term hormone replacement therapy due to panhypopituitarism can lead to serious complications and thus, pituitary transplantation is considered a more desirable. We investigated functional restoration after allotransplatation of the pituitary gland. We transplanted extracted pituitary gland into the omentum of an hypophysectomized rat. Two experiments were performed: (1) to confirm the hypophysectomy was successful and (2) to assess functional restoration after pituitary transplantation. Pituitary hormone level and weight change were consecutively assessed. Electron microscopic (EM) examinations were performed to identify morphological changes at 3 days after transplantation. We confirmed that pituitary gland was properly extracted from 6 rats after sacrifice. The findings showed (1) a weight loss of more than 3% or (2) a weight change of less than 2% along with a decreased growth hormone (GH) level by more than 80% at 2 weeks post-hypophysectomy. A further four rats underwent pituitary transplantation after hypophysectomy and were compared with the previously hypophysectomized rats. All showed rapid weight gain during the two weeks after transplantation. The thyroid-stimulating hormone, prolactin, and GH levels were restored at one week post-transplantation and maintained for 10 weeks. Hypophyseal tissue architecture was maintained at 3 days after transplantation, as indicated by EM. These data suggest that a transplanted pituitary gland can survive in the omentum with concomitant partial restoration of anterior pituitary hormones.
Topics: Allografts; Animals; Body Weight; Hormones; Hypophysectomy; Male; Pituitary Gland; Rats, Sprague-Dawley; Rats
PubMed: 33572839
DOI: 10.3390/cells10020267 -
Journal of Molecular Endocrinology Apr 2015Significant progress has been made recently in unravelling the embryonic events leading to pituitary morphogenesis, both in vivo and in vitro. This includes dissection... (Review)
Review
Significant progress has been made recently in unravelling the embryonic events leading to pituitary morphogenesis, both in vivo and in vitro. This includes dissection of the molecular mechanisms controlling patterning of the ventral diencephalon that regulate formation of the pituitary anlagen or Rathke's pouch. There is also a better characterisation of processes that underlie maintenance of pituitary progenitors, specification of endocrine lineages and the three-dimensional organisation of newly differentiated endocrine cells. Furthermore, a population of adult pituitary stem cells (SCs), originating from embryonic progenitors, have been described and shown to have not only regenerative potential, but also the capacity to induce tumour formation. Finally, the successful recapitulation in vitro of embryonic events leading to generation of endocrine cells from embryonic SCs, and their subsequent transplantation, represents exciting advances towards the use of regenerative medicine to treat endocrine deficits. In this review, an up-to-date description of pituitary morphogenesis will be provided and discussed with particular reference to pituitary SC studies.
Topics: Animals; Gene Expression Regulation, Developmental; Mice; Models, Biological; Morphogenesis; Pituitary Gland; Stem Cells
PubMed: 25587054
DOI: 10.1530/JME-14-0237 -
Hormones (Athens, Greece) 2015Pituitary adenomas are usually benign tumors that cause symptoms by compression of surrounding structures or impaired hormone secretion. Treatment, whether surgical or... (Review)
Review
Pituitary adenomas are usually benign tumors that cause symptoms by compression of surrounding structures or impaired hormone secretion. Treatment, whether surgical or medical depends, on the tumor subtype and degree of compression; however, a significant proportion of patients do not achieve optimal control of mass effects or hormonal hypersecretion. Unraveling the pathogenesis of pituitary adenomas is a critical step in the quest for new subcellular treatment targets that will decrease morbidity and mortality related to these tumors. A large diversity of pathogenetic mechanisms has been described so far including deregulation of cell cycle, molecular pathways and angiogenesis. Major signaling pathways such as Notch, Wnt and Hedgehog, which are mainly active in the early phase of pituitary organogenesis and are essential for the development of somatotrophs, lactotrophs thyrotrophs and corticotrophs, have been implicated in the pathogenesis of pituitary adenomas. In this review we present novel data regarding the role of Notch and Hedgehog regulatory networks in pituitary development and pathogenesis of pituitary adenomas.
Topics: Adenoma; Animals; Hedgehog Proteins; Humans; Pituitary Gland; Pituitary Neoplasms; Receptors, Notch; Signal Transduction
PubMed: 25885100
DOI: 10.1007/BF03401377 -
Nature Reviews. Endocrinology Apr 2013The pituitary gland has a role in puberty, reproduction, stress-adaptive responses, sodium and water balance, uterine contractions, lactation, thyroid function, growth,... (Review)
Review
The pituitary gland has a role in puberty, reproduction, stress-adaptive responses, sodium and water balance, uterine contractions, lactation, thyroid function, growth, body composition and skin pigmentation. Ageing is marked by initially subtle erosion of physiological signalling mechanisms, resulting in lower incremental secretory-burst amplitude, more disorderly patterns of pituitary hormone release and blunted 24 h rhythmic secretion. Almost all pituitary hormones are altered by ageing in humans, often in a manner dependent on sex, body composition, stress, comorbidity, intercurrent illness, medication use, physical frailty, caloric intake, immune status, level of exercise, and neurocognitive decline. The aim of this article is to critically discuss the mechanisms mediating clinical facets of changes in the hypothalamic-pituitary axis during ageing, and the extent to which confounding factors operate to obscure ageing-related effects.
Topics: Aging; Female; Human Growth Hormone; Humans; Male; Pituitary Gland; Pituitary Hormones
PubMed: 23438832
DOI: 10.1038/nrendo.2013.38 -
British Journal of Anaesthesia Jul 2000
Review
Topics: Anesthesia; Humans; Pituitary Gland; Pituitary Neoplasms; Postoperative Care; Preoperative Care
PubMed: 10927991
DOI: 10.1093/bja/85.1.3 -
Genes Mar 2021In mammals, imprinted genes regulate many critical endocrine processes such as growth, the onset of puberty and maternal reproductive behaviour. Human imprinting... (Review)
Review
In mammals, imprinted genes regulate many critical endocrine processes such as growth, the onset of puberty and maternal reproductive behaviour. Human imprinting disorders (IDs) are caused by genetic and epigenetic mechanisms that alter the expression dosage of imprinted genes. Due to improvements in diagnosis, increasing numbers of patients with IDs are now identified and monitored across their lifetimes. Seminal work has revealed that IDs have a strong endocrine component, yet the contribution of imprinted gene products in the development and function of the hypothalamo-pituitary axis are not well defined. Postnatal endocrine processes are dependent upon the production of hormones from the pituitary gland. While the actions of a few imprinted genes in pituitary development and function have been described, to date there has been no attempt to link the expression of these genes as a class to the formation and function of this essential organ. This is important because IDs show considerable overlap, and imprinted genes are known to define a transcriptional network related to organ growth. This knowledge deficit is partly due to technical difficulties in obtaining useful transcriptomic data from the pituitary gland, namely, its small size during development and cellular complexity in maturity. Here we utilise high-sensitivity RNA sequencing at the embryonic stages, and single-cell RNA sequencing data to describe the imprinted transcriptome of the pituitary gland. In concert, we provide a comprehensive literature review of the current knowledge of the role of imprinted genes in pituitary hormonal pathways and how these relate to IDs. We present new data that implicate imprinted gene networks in the development of the gland and in the stem cell compartment. Furthermore, we suggest novel roles for individual imprinted genes in the aetiology of IDs. Finally, we describe the dynamic regulation of imprinted genes in the pituitary gland of the pregnant mother, with implications for the regulation of maternal metabolic adaptations to pregnancy.
Topics: Animals; DNA Methylation; Female; Gene Expression Profiling; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Genomic Imprinting; Humans; Mice; Pituitary Gland; Pregnancy; Sequence Analysis, RNA; Single-Cell Analysis
PubMed: 33808370
DOI: 10.3390/genes12040509 -
American Journal of Physiology.... Jun 2019Circulating myostatin-attenuating agents are being developed to treat muscle-wasting disease despite their potential to produce serious off-target effects, as...
Circulating myostatin-attenuating agents are being developed to treat muscle-wasting disease despite their potential to produce serious off-target effects, as myostatin/activin receptors are widely distributed among many nonmuscle tissues. Our studies suggest that the myokine not only inhibits striated muscle growth but also regulates pituitary development and growth hormone (GH) action in the liver. Using a novel myostatin-null label-retaining model (Jekyll mice), we determined that the heterogeneous pool of pituitary stem, transit-amplifying, and progenitor cells in Jekyll mice depletes more rapidly after birth than the pool in wild-type mice. This correlated with increased levels of GH, prolactin, and the cells that secrete these hormones, somatotropes and lactotropes, respectively, in Jekyll pituitaries. Recombinant myostatin also stimulated GH release and gene expression in pituitary cell cultures although inhibiting prolactin release. In primary hepatocytes, recombinant myostatin blocked GH-stimulated expression of two key mediators of growth, insulin-like growth factor (IGF)1 and the acid labile subunit and increased expression of an inhibitor, IGF-binding protein-1. The significance of these findings was demonstrated by smaller muscle fiber size in a model lacking myostatin and liver IGF1 expression (LID-o-Mighty mice) compared with that in myostatin-null (Mighty) mice. These data together suggest that myostatin may regulate pituitary development and function and that its inhibitory actions in muscle may be partly mediated by attenuating GH action in the liver. They also suggest that circulating pharmacological inhibitors of myostatin could produce unintended consequences in these and possibly other tissues.
Topics: Animals; Cachexia; Carrier Proteins; Drug Development; Glycoproteins; Growth Hormone; Hepatocytes; Humans; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Lactotrophs; Liver; Mice; Mice, Knockout; Models, Animal; Myostatin; Pituitary Gland; Primary Cell Culture; Prolactin; Recombinant Proteins; Somatotrophs; Stem Cells
PubMed: 30888862
DOI: 10.1152/ajpendo.00001.2019 -
Cell Reports Jun 2023Gonadotropes in the anterior pituitary gland are essential for fertility and provide a functional link between the brain and the gonads. To trigger ovulation,...
Gonadotropes in the anterior pituitary gland are essential for fertility and provide a functional link between the brain and the gonads. To trigger ovulation, gonadotrope cells release massive amounts of luteinizing hormone (LH). The mechanism underlying this remains unclear. Here, we utilize a mouse model expressing a genetically encoded Ca indicator exclusively in gonadotropes to dissect this mechanism in intact pituitaries. We demonstrate that female gonadotropes exclusively exhibit a state of hyperexcitability during the LH surge, resulting in spontaneous [Ca] transients in these cells, which persist in the absence of any in vivo hormonal signals. L-type Ca channels and transient receptor potential channel A1 (TRPA1) together with intracellular reactive oxygen species (ROS) levels ensure this state of hyperexcitability. Consistent with this, virus-assisted triple knockout of Trpa1 and L-type Ca subunits in gonadotropes leads to vaginal closure in cycling females. Our data provide insight into molecular mechanisms required for ovulation and reproductive success in mammals.
Topics: Mice; Animals; Female; Gonadotrophs; Pituitary Gland, Anterior; Luteinizing Hormone; Pituitary Gland; Ovulation; Mammals
PubMed: 37224016
DOI: 10.1016/j.celrep.2023.112543 -
Cellular and Molecular Life Sciences :... Oct 1998Anterior pituitary differentiation is a well-established paradigm in mammalian organogenesis. PIT1/GHF1, a homoeotic gene, plays a key role in terminal pituitary... (Review)
Review
Anterior pituitary differentiation is a well-established paradigm in mammalian organogenesis. PIT1/GHF1, a homoeotic gene, plays a key role in terminal pituitary differentiation. Recently, a new set of transcription factors involved in early pituitary differentiation have been identified: Lhx-3, Lhx-4, P-OTX and Prop1. A pituitary-specific transcriptional cascade regulating a developmental programme leads to the determination of the mature cell types.
Topics: Animals; DNA-Binding Proteins; Gene Expression Regulation, Developmental; Homeodomain Proteins; Humans; Pituitary Gland; Transcription Factor Pit-1; Transcription Factors
PubMed: 9817984
DOI: 10.1007/s000180050234