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Frontiers of Medicine Feb 2023A long-held belief is that pituitary hormones bind to their cognate receptors in classical target glands to actuate their manifold functions. However, a number of... (Review)
Review
A long-held belief is that pituitary hormones bind to their cognate receptors in classical target glands to actuate their manifold functions. However, a number of studies have shown that multiple types of pituitary hormone receptors are widely expressed in non-classical target organs. Each pituitary gland-derived hormone exhibits a wide range of nonconventional biological effects in these non-classical target organs. Herein, the extra biological functions of pituitary hormones, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, adrenocorticotrophic hormone, and prolactin when they act on non-classical organs were summarized, defined by the novel concept of an "atypical pituitary hormone-target tissue axis." This novel proposal explains the pathomechanisms of abnormal glucose and lipid metabolism, obesity, hypertension, fatty liver, and atherosclerosis while offering a more comprehensive and systematic insights into the coordinated regulation of environmental factors, genetic factors, and neuroendocrine hormones on human biological functions. The continued exploration of the physiology of the "atypical pituitary hormone-target tissue axis" could enable the identification of novel therapeutic targets for metabolic diseases.
Topics: Humans; Pituitary Hormones; Luteinizing Hormone; Follicle Stimulating Hormone; Prolactin; Pituitary Gland
PubMed: 36849623
DOI: 10.1007/s11684-022-0973-7 -
Reviews in Endocrine & Metabolic... Jun 2024Hypopituitarism, or the failure to secrete hormones produced by the anterior pituitary (adenohypophysis) and/or to release hormones from the posterior pituitary... (Review)
Review
Hypopituitarism, or the failure to secrete hormones produced by the anterior pituitary (adenohypophysis) and/or to release hormones from the posterior pituitary (neurohypophysis), can be congenital or acquired. When more than one pituitary hormone axis is impaired, the condition is known as combined pituitary hormone deficiency (CPHD). The deficiency may be primarily due to a hypothalamic or to a pituitary disorder, or concomitantly both, and has a negative impact on target organ function. This review focuses on the pathophysiology, diagnosis and management of anterior pituitary hormone deficiency in the pediatric age. Congenital hypopituitarism is generally due to genetic disorders and requires early medical attention. Exposure to toxicants or intrauterine infections should also be considered as potential etiologies. The molecular mechanisms underlying the fetal development of the hypothalamus and the pituitary are well characterized, and variants in the genes involved therein may explain the pathophysiology of congenital hypopituitarism: mutations in the genes expressed in the earliest stages are usually associated with syndromic forms whereas variants in genes involved in later stages of pituitary development result in non-syndromic forms with more specific hormone deficiencies. Tumors or lesions of the (peri)sellar region, cranial radiation therapy, traumatic brain injury and, more rarely, other inflammatory or infectious lesions represent the etiologies of acquired hypopituitarism. Hormone replacement is the general strategy, with critical periods of postnatal life requiring specific attention.
Topics: Humans; Hypopituitarism; Child; Pituitary Hormones, Anterior
PubMed: 38112850
DOI: 10.1007/s11154-023-09868-4 -
Frontiers in Endocrinology 2021Pituitary hormone axes modulate glucose metabolism and exert direct or indirect effects on insulin secretion and function. Cortisol and growth hormone are potent... (Review)
Review
Pituitary hormone axes modulate glucose metabolism and exert direct or indirect effects on insulin secretion and function. Cortisol and growth hormone are potent insulin-antagonistic hormones. Therefore impaired glucose tolerance, elevated fasting glucose concentrations and diabetes mellitus are frequent in Cushing's disease and acromegaly. Also prolactinomas, growth hormone (GH) deficiency, hypogonadism and hypothyroidism might be associated with impaired glucose homeostasis but usually to a lesser extent. Therefore glucose metabolism needs to be closely monitored and treated in patients with pituitary adenomas. Correction of the pituitary dysfunction is frequently followed by improvement of glucose homeostasis.
Topics: Blood Glucose; Glucose Intolerance; Humans; Hypopituitarism; Insulin; Pituitary Hormones
PubMed: 33995272
DOI: 10.3389/fendo.2021.626427 -
Journal of Endocrinological... Jan 2015Over the last two decades, the understanding of the mechanisms involved in pituitary ontogenesis has largely increased. Since the first description of POU1F1 human... (Review)
Review
Over the last two decades, the understanding of the mechanisms involved in pituitary ontogenesis has largely increased. Since the first description of POU1F1 human mutations responsible for a well-defined phenotype without extra-pituitary malformation, several other genetic defects of transcription factors have been reported with variable degrees of phenotype-genotype correlations. However, to date, despite the identification of an increased number of genetic causes of isolated or multiple pituitary deficiencies, the etiology of most (80-90 %) congenital cases of hypopituitarism remains unsolved. Identifying new etiologies is of importance as a post-natal diagnosis to better diagnose and treat the patients (delayed pituitary deficiencies, differential diagnosis of a pituitary mass on MRI, etc.), and as a prenatal diagnosis to decrease the risk of early death (undiagnosed corticotroph deficiency for instance). The aim of this review is to summarize the main etiologies and phenotypes of combined pituitary hormone deficiencies, associated or not with extra-pituitary anomalies, and to suggest how the identification of such etiologies could be improved in the near future.
Topics: Animals; Forecasting; Humans; Hypopituitarism; Mutation; Phenotype; Pituitary Gland; Pituitary Hormones
PubMed: 25200994
DOI: 10.1007/s40618-014-0141-2 -
Frontiers in Endocrinology 2022Combined pituitary hormone deficiency (CPHD) is not a rare disorder, with a frequency of approximately 1 case per 4,000 live births. However, in most cases, a genetic... (Review)
Review
Combined pituitary hormone deficiency (CPHD) is not a rare disorder, with a frequency of approximately 1 case per 4,000 live births. However, in most cases, a genetic diagnosis is not available. Furthermore, the diagnosis is challenging because no clear correlation exists between the pituitary hormones affected and the gene(s) responsible for the disorder. Next-generation sequencing (NGS) has recently been widely used to identify novel genes that cause (or putatively cause) CPHD. This review outlines causative genes for CPHD that have been newly reported in recent years. Moreover, novel variants of known CPHD-related genes ( and genes) that contribute to CPHD through unique mechanisms are also discussed in this review. From a clinical perspective, variants in some of the recently identified causative genes result in extra-pituitary phenotypes. Clinical research on the related symptoms and basic research on pituitary formation may help in inferring the causative gene(s) of CPHD. Future NGS analysis of a large number of CPHD cases may reveal new genes related to pituitary development. Clarifying the causative genes of CPHD may help to understand the process of pituitary development. We hope that future innovations will lead to the identification of genes responsible for CPHD and pituitary development.
Topics: High-Throughput Nucleotide Sequencing; Humans; Hypopituitarism; Pituitary Hormones; Transcription Factors
PubMed: 36237189
DOI: 10.3389/fendo.2022.1008306 -
Seminars in Reproductive Medicine 2000Hereditary forms of pituitary insufficiency not associated with anatomic defects of the central nervous system, hypothalamus, or pituitary are a heterogeneous group of... (Review)
Review
Hereditary forms of pituitary insufficiency not associated with anatomic defects of the central nervous system, hypothalamus, or pituitary are a heterogeneous group of disorders that result from interruptions at different points in the hypothalamic-pituitary-somatomedin-peripheral tissue axis. These different types of pituitary dwarfism can be classified on the level of the defect; mode of inheritance; whether the phenotype is isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiency (CPHD); whether the hormone is absent, deficient, or abnormal; and, in patients with GH resistance, whether insulin-like growth factor 1 (IGF1) is deficient due to GH receptor or IGF1 defects. Information on each disorder is summarized. More detailed information can be obtained through the electronic database Online Mendelian Inheritance in Man which is available at http://www3.ncbi.nlm.nih.gov/Omim/.
Topics: Drug Resistance; Dwarfism, Pituitary; Human Growth Hormone; Humans; Hypopituitarism; Mutation; Pituitary Hormones; Receptors, Somatotropin
PubMed: 11299517
DOI: 10.1055/s-2000-13473 -
Journal of Molecular Endocrinology Jun 2011The pituitary gland produces hormones that play important roles in both the development and the homeostasis of the body. A deficiency of two or several of these... (Review)
Review
The pituitary gland produces hormones that play important roles in both the development and the homeostasis of the body. A deficiency of two or several of these pituitary hormones, known as combined pituitary hormone deficiency, may present in infants or children due to an unknown etiology and is considered congenital or idiopathic. Advancements in our understanding of pituitary development have provided a genetic basis to explain the pathophysiological basis of pituitary hormone disease. Nevertheless, there are several challenges to the precise characterization of abnormal genotypes; these exist secondary to the complexities of several of the hypothalamic/pituitary developmental factors and signals, which ultimately integrate in a temporal and spatial dependent manner to produce a mature gland. Furthermore, the clinical presentation of pituitary hormone disease may be dynamic as subsequent hormone deficiencies may develop over time. The characterization of patients with mutations in genes responsible for pituitary development provides an opportunity to discover potential novel mechanisms responsible for pituitary pathophysiology. The focus of this review is to report the most recent mutations in genes responsible for pituitary development in patients with hypopituitarism and emphasize the importance to physicians and researchers for characterizing these patients. Continuing efforts toward understanding the molecular basis of pituitary development as well as genetic screening of patients with pituitary disease will offer new insights into both diagnostic and potential therapeutic options that will decrease the morbidity and mortality in patients with hypopituitarism.
Topics: Animals; Child; Gene Expression Regulation, Developmental; Humans; Hypopituitarism; Infant; Mutation; Pituitary Gland; Pituitary Hormones; Transcription Factors
PubMed: 21447626
DOI: 10.1530/JME-10-0133 -
Progress in Molecular Biology and... 2016The long-held belief that pituitary hormones act solely on master targets was first questioned when we documented G protein-coupled receptors for thyroid-stimulating... (Review)
Review
The long-held belief that pituitary hormones act solely on master targets was first questioned when we documented G protein-coupled receptors for thyroid-stimulating hormone, follicle-stimulating hormone, adrenocorticotrophic hormone, oxytocin, and vasopressin on bone cells. These evolutionarily conserved hormones and their receptors are known to have primitive roles, and exist in invertebrate species as far down as coelenterates. It is not surprising therefore that each such hormone has multiple hitherto unrecognized functions in mammalian integrative physiology, and hence, becomes a potential target for therapeutic intervention. Here we discuss the skeletal actions of pituitary hormones.
Topics: Animals; Biological Evolution; Bone Resorption; Bone and Bones; Humans; Pituitary Hormones; Reproduction; Signal Transduction
PubMed: 27697202
DOI: 10.1016/bs.pmbts.2016.08.004 -
Nature Reviews. Endocrinology Dec 2023Traditional textbook physiology has ascribed unitary functions to hormones from the anterior and posterior pituitary gland, mainly in the regulation of effector hormone... (Review)
Review
Traditional textbook physiology has ascribed unitary functions to hormones from the anterior and posterior pituitary gland, mainly in the regulation of effector hormone secretion from endocrine organs. However, the evolutionary biology of pituitary hormones and their receptors provides evidence for a broad range of functions in vertebrate physiology. Over the past decade, we and others have discovered that thyroid-stimulating hormone, follicle-stimulating hormone, adrenocorticotropic hormone, prolactin, oxytocin and arginine vasopressin act directly on somatic organs, including bone, adipose tissue and liver. New evidence also indicates that pituitary hormone receptors are expressed in brain regions, nuclei and subnuclei. These studies have prompted us to attribute the pathophysiology of certain human diseases, including osteoporosis, obesity and neurodegeneration, at least in part, to changes in pituitary hormone levels. This new information has identified actionable therapeutic targets for drug discovery.
Topics: Humans; Pituitary Hormones; Pituitary Gland; Prolactin; Adipose Tissue; Brain
PubMed: 37715028
DOI: 10.1038/s41574-023-00894-5 -
The Journal of Nutrition Apr 2000Numerous studies have shown that the administration of a glutamate receptor agonist or a high dose of glutamate stimulates pituitary hormone secretion in animals.... (Review)
Review
Numerous studies have shown that the administration of a glutamate receptor agonist or a high dose of glutamate stimulates pituitary hormone secretion in animals. However, only a single human study has reported that an oral load of glutamic acid induced the secretion of prolactin and probably adrenocorticotropic hormone (ACTH) (but not other pituitary hormones). Because of glutamate's use in foods as monosodium glutamate (MSG), a flavoring agent, and the limited amount of human data, we studied the effect of a large oral dose of MSG in humans on the secretion of prolactin and other pituitary hormones. Fasting male subjects bearing venous catheters received on separate days each of the following four treatments: a vehicle, MSG (12.7 g), a high protein meal (a physiologic stimulus of prolactin secretion) by mouth, or an intravenous infusion of thyrotropin-releasing hormone (TRH, a pharmacologic stimulus of prolactin secretion). Plasma hormone responses were quantitated by RIA at 20-min intervals for 4 h. The protein meal induced a modest increase and TRH infusion a substantial increase in plasma prolactin, whereas MSG ingestion did not. MSG ingestion also did not raise the plasma concentrations of any of the other pituitary hormones measured (luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, growth hormone) or of cortisol. Ingestion of MSG raised plasma glutamate concentrations 11-fold; the protein meal did not raise plasma glutamate. The results demonstrate that MSG ingestion in humans does not modify anterior pituitary hormone secretion. One implication is that diet-derived glutamate may not penetrate into hypothalamic regions controlling anterior pituitary function.
Topics: Administration, Oral; Animals; Dose-Response Relationship, Drug; Food Additives; Humans; Male; Pituitary Hormones; Reference Values; Sodium Glutamate
PubMed: 10736381
DOI: 10.1093/jn/130.4.1053S