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Frontiers in Endocrinology 2022The pituitary is a master gland responsible for the modulation of critical endocrine functions. Pituitary neuroendocrine tumours (PitNETs) display a considerable... (Review)
Review
The pituitary is a master gland responsible for the modulation of critical endocrine functions. Pituitary neuroendocrine tumours (PitNETs) display a considerable prevalence of 1/1106, frequently observed as benign solid tumours. PitNETs still represent a cause of important morbidity, due to hormonal systemic deregulation, with surgical, radiological or chronic treatment required for illness management. The apparent scarceness, uncommon behaviour and molecular features of PitNETs have resulted in a relatively slow progress in depicting their pathogenesis. An appropriate interpretation of different phenotypes or cellular outcomes during tumour growth is desirable, since histopathological characterization still remains the main option for prognosis elucidation. Improved knowledge obtained in recent decades about pituitary tumorigenesis has revealed that this process involves several cellular routes in addition to proliferation and death, with its modulation depending on many signalling pathways rather than being the result of abnormalities of a unique proliferation pathway, as sometimes presented. PitNETs can display intrinsic heterogeneity and cell subpopulations with diverse biological, genetic and epigenetic particularities, including tumorigenic potential. Hence, to obtain a better understanding of PitNET growth new approaches are required and the systematization of the available data, with the role of cell death programs, autophagy, stem cells, cellular senescence, mitochondrial function, metabolic reprogramming still being emerging fields in pituitary research. We envisage that through the combination of molecular, genetic and epigenetic data, together with the improved morphological, biochemical, physiological and metabolically knowledge on pituitary neoplastic potential accumulated in recent decades, tumour classification schemes will become more accurate regarding tumour origin, behaviour and plausible clinical results.
Topics: Cellular Senescence; Humans; Neuroendocrine Tumors; Pituitary Gland; Pituitary Neoplasms; Signal Transduction
PubMed: 35837315
DOI: 10.3389/fendo.2022.924942 -
Cellular and Molecular Life Sciences :... Mar 2021The pituitary plays a pivotal role in maintaining systemic homeostasis by secreting several hormones. During fetal development, the pituitary develops from the oral... (Review)
Review
The pituitary plays a pivotal role in maintaining systemic homeostasis by secreting several hormones. During fetal development, the pituitary develops from the oral ectoderm in contact with the adjacent hypothalamus. This process is regulated by the fine-tuned expression of transcription and growth factors. Impairments of this process result in congenital pituitary hypoplasia leading to dysfunction of the pituitary. Although animal models such as knockout mice have helped to clarify these underlying mechanisms, the developmental processes of the human pituitary gland and the mechanisms of human pituitary disorders have not been fully understood. This is because, at least in part, of the lack of a human pituitary developmental model. Recently, methods for in vitro induction of the pituitary gland from human pluripotent stem cells were developed. These models can be utilized not only for regenerative medicine but also for human pituitary studies on developmental biology and for modeling of pituitary disorders, such as hypopituitarism and pituitary tumors. In this review, we provide an overview of recent progress in the applications of pluripotent stem cells for pituitary research and discuss further perspectives for pituitary studies.
Topics: Animals; Cell Culture Techniques; Cell Differentiation; Cells, Cultured; Humans; Induced Pluripotent Stem Cells; Pituitary Diseases; Pituitary Gland; Pluripotent Stem Cells; Regenerative Medicine
PubMed: 33206204
DOI: 10.1007/s00018-020-03692-8 -
World Neurosurgery Dec 2023Located at the base of the skull, the pituitary gland has a long and controversial history, not only in terms of its anatomy, but especially in the functions it performs... (Review)
Review
Located at the base of the skull, the pituitary gland has a long and controversial history, not only in terms of its anatomy, but especially in the functions it performs and in the attempt to approach it surgically. Considered by Galen of Pergamon to have a role in releasing waste products of the brain, a theory accepted until the 17th century, the pituitary gland became a separate entity once with the anatomical descriptions of the famous Andreas Vesalius. At the beginning of the 18th century, researches of the time began to be more and more interested in this gland, trying to identify its functions, and at the same time correcting the traditional theories that were wrong or incomplete. Later, they turned their attention to experimental animal studies that represented the germinal nucleus for the transcranial and endoscopic pituitary surgery. In this review, an attempt has been made to record the entire history of anatomy, physiology and surgery of the pituitary gland, from antiquity to the current day's surgical techniques.
Topics: Animals; Pituitary Gland; Hypophysectomy; Endoscopy; Skull; Head
PubMed: 37683915
DOI: 10.1016/j.wneu.2023.09.004 -
Nature Communications Feb 2023Inter-organ communication is a major hallmark of health and is often orchestrated by hormones released by the anterior pituitary gland. Pituitary gonadotropes secrete...
Inter-organ communication is a major hallmark of health and is often orchestrated by hormones released by the anterior pituitary gland. Pituitary gonadotropes secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to regulate gonadal function and control fertility. Whether FSH and LH also act on organs other than the gonads is debated. Here, we find that gonadotrope depletion in adult female mice triggers profound hypogonadism, obesity, glucose intolerance, fatty liver, and bone loss. The absence of sex steroids precipitates these phenotypes, with the notable exception of fatty liver, which results from ovary-independent actions of FSH. We uncover paracrine FSH action on pituitary corticotropes as a mechanism to restrain the production of corticosterone and prevent hepatic steatosis. Our data demonstrate that functional communication of two distinct hormone-secreting cell populations in the pituitary regulates hepatic lipid metabolism.
Topics: Mice; Female; Animals; Lipid Metabolism; Follicle Stimulating Hormone; Pituitary Gland; Luteinizing Hormone; Fatty Liver
PubMed: 36841874
DOI: 10.1038/s41467-023-36681-z -
Nature Reviews. Endocrinology Feb 2024Pituitary cells that express the transcription factor SOX2 are stem cells because they can self-renew and differentiate into multiple pituitary hormone-producing cell... (Review)
Review
Pituitary cells that express the transcription factor SOX2 are stem cells because they can self-renew and differentiate into multiple pituitary hormone-producing cell types as organoids. Wounding and physiological challenges can activate pituitary stem cells, but cell numbers are not fully restored, and the ability to mobilize stem cells decreases with increasing age. The basis of these limitations is still unknown. The regulation of stem cell quiescence and activation involves many different signalling pathways, including those mediated by WNT, Hippo and several cytokines; more research is needed to understand the interactions between these pathways. Pituitary organoids can be formed from human or mouse embryonic stem cells, or from human induced pluripotent stem cells. Human pituitary organoid transplantation is sufficient to induce corticosterone release in hypophysectomized mice, raising the possibility of therapeutic applications. Today, pituitary organoids have the potential to assess the role of individual genes and genetic variants on hormone production ex vivo, providing an important tool for the advancement of exciting frontiers in pituitary stem cell biology and pituitary organogenesis. In this article, we provide an overview of notable discoveries in pituitary stem cell function and highlight important areas for future research.
Topics: Humans; Animals; Mice; Induced Pluripotent Stem Cells; Pituitary Gland; Transcription Factors; Signal Transduction; Cell Differentiation
PubMed: 38102391
DOI: 10.1038/s41574-023-00922-4 -
Endocrinology Apr 2023The pituitary gland regulates growth, metabolism, reproduction, the stress response, uterine contractions, lactation, and water retention. It secretes hormones in...
The pituitary gland regulates growth, metabolism, reproduction, the stress response, uterine contractions, lactation, and water retention. It secretes hormones in response to hypothalamic input, end organ feedback, and diurnal cues. The mechanisms by which pituitary stem cells are recruited to proliferate, maintain quiescence, or differentiate into specific cell types, especially thyrotropes, are not well understood. We used single-cell RNA sequencing in juvenile P7 mouse pituitary cells to identify novel factors in pituitary cell populations, with a focus on thyrotropes and rare subtypes. We first observed cells coexpressing markers of both thyrotropes and gonadotropes, such as Pou1f1 and Nr5a1. This was validated in vivo by both immunohistochemistry and lineage tracing of thyrotropes derived from Nr5a1-Cre; mTmG mice and demonstrates that Nr5a1-progenitors give rise to a proportion of thyrotropes during development. Our data set also identifies novel factors expressed in pars distalis and pars tuberalis thyrotropes, including the Shox2b isoform in all thyrotropes and Sox14 specifically in Pou1f1-negative pars tuberalis thyrotropes. We have therefore used single-cell transcriptomics to determine a novel developmental trajectory for thyrotropes and potential novel regulators of thyrotrope populations.
Topics: Pregnancy; Female; Mice; Animals; Thyrotropin; Pituitary Gland; Transcription Factors; Pituitary Diseases; Immunohistochemistry; Pituitary Gland, Anterior; SOXB2 Transcription Factors
PubMed: 37183548
DOI: 10.1210/endocr/bqad076 -
Biochemical and Biophysical Research... Jul 2022This study investigates the function of Elp1 and Elongator in the pituitary gland. Two conditional knockout models were generated where Elp1 was selectively deleted in...
This study investigates the function of Elp1 and Elongator in the pituitary gland. Two conditional knockout models were generated where Elp1 was selectively deleted in either somatotropes of the anterior pituitary or Pomc-expressing cells of the anterior and intermediate pituitary. Although loss of Elp1 in somatotropes did not significantly impact murine growth or development, its loss in Pomc-expressing cells resulted in dramatically reduced levels of α-MSH, hyperphagia and obesity. This report provides the first evidence that Elongator plays an essential role in regulating the melanocortin satiety pathway.
Topics: Animals; Melanocortins; Mice; Obesity; Pituitary Gland; Pro-Opiomelanocortin; alpha-MSH
PubMed: 35537288
DOI: 10.1016/j.bbrc.2022.04.128 -
Endocrine Journal Jan 2024Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) in several organs including endocrine glands. Among endocrine irAEs, thyroid and... (Review)
Review
Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) in several organs including endocrine glands. Among endocrine irAEs, thyroid and pituitary irAEs are frequently observed, followed by primary adrenal insufficiency, insulin-dependent diabetes mellitus, and hypoparathyroidism. These conditions could lead to life-threatening consequences, such as adrenal crisis and diabetic ketoacidosis. On the other hand, several types of irAEs including thyroid and pituitary irAEs are reported to be associated with better overall survival. Therefore, it is important to understand and manage endocrine irAEs, which differ depending on the ICI regimen used. In this review, we describe the clinical features, potential biomarkers, management strategies, and possible mechanisms of thyroid and pituitary irAEs.
Topics: Humans; Thyroid Gland; Pituitary Gland; Pituitary Diseases; Biomarkers; Diabetes Mellitus, Type 1; Neoplasms
PubMed: 37940567
DOI: 10.1507/endocrj.EJ23-0524 -
Endocrine Aug 2023Transsphenoidal surgery for non-functioning pituitary adenomas (NFPAs) can alter pituitary function. We assessed the rates of improvement and deterioration of pituitary... (Review)
Review
PURPOSE
Transsphenoidal surgery for non-functioning pituitary adenomas (NFPAs) can alter pituitary function. We assessed the rates of improvement and deterioration of pituitary function by axis and searched for predictive factors of these outcomes.
METHODS
We reviewed consecutive medical files from patients having had transsphenoidal surgery for NFPA between 2004 and 2018. Pituitary functions and MRI imaging were analyzed prior and after surgery. The occurrence of recovery and new deficit were documented per axis. Prognostic factors of hormonal recovery and new deficits were searched.
RESULTS
Among 137 patients analyzed, median tumor size of the NFPA was 24.8 mm and 58.4% of patients presented visual impairment. Before surgery, 91 patients (67%) had at least one abnormal pituitary axis (hypogonadism: 62.4%; hypothyroidism: 41%, adrenal insufficiency: 30.8%, growth hormone deficiency: 29.9%; increased prolactin: 50.8%). Following surgery, the recovery rate of pituitary deficiency of one axis or more was 46% and the rate of new pituitary deficiency was 10%. Rates of LH-FSH, TSH, ACTH and GH deficiency recovery were 35.7%, 30.4%, 15.4%, and 45.5% respectively. Rates of new LH-FSH, TSH, ACTH and GH deficiencies were 8.3%, 1.6%, 9.2% and 5.1% respectively. Altogether, 24.6% of patients had a global pituitary function improvement and only 7% had pituitary function worsening after surgery. Male patients and patients with hyperprolactinemia upon diagnosis were more likely to experience pituitary function recovery. No prognostic factors for the risk of new deficiencies were identified.
CONCLUSION
In a real-life cohort of patients with NFPAs, recovery of hypopituitarism after surgery is more frequent than the occurrence of new deficiencies. Hence, hypopituitarism could be considered a relative indication for surgery in patients with NFPAs.
Topics: Humans; Male; Pituitary Gland; Hypopituitarism; Pituitary Neoplasms; Follicle Stimulating Hormone; Thyrotropin; Adrenocorticotropic Hormone
PubMed: 37222882
DOI: 10.1007/s12020-023-03400-z -
Hormones (Athens, Greece) Mar 2023
Topics: Humans; COVID-19; Diabetes Mellitus, Type 2; Adrenal Gland Diseases; Pituitary Diseases; Pituitary Gland; Endocrine System Diseases; Diabetes Mellitus
PubMed: 36864344
DOI: 10.1007/s42000-023-00436-8