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Frontiers in Endocrinology 2022Growth hormone (GH) is mainly secreted by eosinophils of anterior pituitary gland. GH plays an important role in regulating the growth and development of many tissues... (Review)
Review
Growth hormone (GH) is mainly secreted by eosinophils of anterior pituitary gland. GH plays an important role in regulating the growth and development of many tissues and cells, so it is used in the treatment of many diseases. In recent years, the regulation of GH on ovarian function has attracted much attention. GH has been applied in controlled ovarian hyperstimulation, particularly in the patients with advanced age, diminished ovarian reserve (DOR) and poor ovarian response (POR). GH can directly bind to the growth hormone receptor (GHR) on the ovary to promote the growth, maturation and ovulation of follicles, as well as to inhibit follicular atresia. GH so as to promote the occurrence of early follicles, enhance the sensitivity of follicles to gonadotropins, accelerate the maturation of oocyte nucleus, improve mitochondrial activity and the quality of oocytes through the insulin-like growth factor (IGF) system, which is an indirect regulation. The deep-seated effects of GH on human reproduction and ovarian aging need further basic research and clinical practice.
Topics: Female; Humans; Growth Hormone; Ovary; Follicular Atresia; Human Growth Hormone; Aging
PubMed: 36699044
DOI: 10.3389/fendo.2022.1072313 -
Frontiers in Endocrinology 2022
Topics: Growth Disorders; Human Growth Hormone; Humans
PubMed: 36176472
DOI: 10.3389/fendo.2022.1013872 -
Discovery Medicine Jun 2014Acromegaly is a disease characterized by growth hormone (GH) excess originating, in approximately 95% of cases, from a somatotroph pituitary adenoma. Symptomatology and... (Review)
Review
Acromegaly is a disease characterized by growth hormone (GH) excess originating, in approximately 95% of cases, from a somatotroph pituitary adenoma. Symptomatology and clinical features are due to GH and insulin-like growth factor 1 excess; unfortunately, for most patients diagnosis is delayed by several years. Acromegaly patients' morbidity and mortality are higher than those of the normal population. However, with adequate biochemical control mortality rates can be restored to normal. Tumor size and location, symptoms, comorbidities, and lastly, but not least, patient preference, are all important aspects in treatment decision making, and treatment approach should be individualized. Current therapy includes medical, surgical, and radiation. This review focuses on recent significant developments in medical therapy. There are three major therapeutic drug classes: somatostatin receptor ligands (SRLs), which represent the mainstay of medical therapy, GH receptor blockers, and dopamine agonists. Multi-ligand receptor SRLs such as pasireotide, should increase therapeutic choices for acromegaly patients currently uncontrolled on available SRLs. Furthermore, significant research has been focused in the development of novel delivery modalities (e.g., oral and long acting subcutaneous administration).
Topics: Acromegaly; Dopamine Agonists; Drug Therapy; Drug Therapy, Combination; Human Growth Hormone; Humans; Receptors, Somatostatin
PubMed: 24979253
DOI: No ID Found -
International Journal of Obesity and... Mar 1999Growth hormone (GH) secretion, either spontaneous or evoked by provocative stimuli, is markedly blunted in obesity. In fact obese patients display, compared to normal... (Review)
Review
Growth hormone (GH) secretion, either spontaneous or evoked by provocative stimuli, is markedly blunted in obesity. In fact obese patients display, compared to normal weight subjects, a reduced half-life, frequency of secretory episodes and daily production rate of the hormone. Furthermore, in these patients GH secretion is impaired in response to all traditional pharmacological stimuli acting at the hypothalamus (insulin-induced hypoglycaemia, arginine, galanin, L-dopa, clonidine, acute glucocorticoid administration) and to direct somatotrope stimulation by exogenous growth hormone releasing hormone (GHRH). Compounds thought to inhibit hypothalamic somatostatin (SRIH) release (pyridostigmine, arginine, galanin, atenolol) consistently improve, though do not normalize, the somatotropin response to GHRH in obesity. The synthetic growth hormone releasing peptides (GHRPs) GHRP-6 and hexarelin elicit in obese patients GH responses greater than those evoked by GHRH, but still lower than those observed in lean subjects. The combined administration of GHRH and GHRP-6 represents the most powerful GH releasing stimulus known in obesity, but once again it is less effective in these patients than in lean subjects. As for the peripheral limb of the GH-insulin-like growth factor I (IGF-I) axis, high free IGF-I, low IGF-binding proteins 1 (IGFBP-1) and 2 (IGFBP-2), normal or high IGFBP-3 and increased GH binding protein (GHBP) circulating levels have been described in obesity. Recent evidence suggests that leptin, the product of adipocyte specific ob gene, exerts a stimulating effect on GH release in rodents; should the same hold true in man, the coexistence of high leptin and low GH serum levels in human obesity would fit in well with the concept of a leptin resistance in this condition. Concerning the influence of metabolic and nutritional factors, an impaired somatotropin response to hypoglycaemia and a failure of glucose load to inhibit spontaneous and stimulated GH release are well documented in obese patients; furthermore, drugs able to block lipolysis and thus to lower serum free fatty acids (NEFA) significantly improve somatotropin secretion in obesity. Caloric restriction and weight loss are followed by the restoration of a normal spontaneous and stimulated GH release. On the whole, hypothalamic, pituitary and peripheral factors appear to be involved in the GH hyposecretion of obesity. A SRIH hypertone, a GHRH deficiency or a functional failure of the somatotrope have been proposed as contributing factors. A lack of the putative endogenous ligand for GHRP receptors is another challenging hypothesis. On the peripheral side, the elevated plasma levels of NEFA and free IGF-I may play a major role. Whatever the cause, the defect of GH secretion in obesity appears to be of secondary, probably adaptive, nature since it is completely reversed by the normalization of body weight. In spite of this, treatment with biosynthetic GH has been shown to improve the body composition and the metabolic efficacy of lean body mass in obese patients undergoing therapeutic severe caloric restriction. GH and conceivably GHRPs might therefore have a place in the therapy of obesity.
Topics: Body Composition; Diet, Reducing; Growth Hormone-Releasing Hormone; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Leptin; Nutritional Physiological Phenomena; Obesity; Proteins; Weight Loss
PubMed: 10193871
DOI: 10.1038/sj.ijo.0800807 -
Protein Science : a Publication of the... Sep 2023Recombinant human growth hormone (rhGH) and GH receptor antagonists (GHAs) are used clinically to treat a range of disorders associated with GH deficiency or... (Review)
Review
Recombinant human growth hormone (rhGH) and GH receptor antagonists (GHAs) are used clinically to treat a range of disorders associated with GH deficiency or hypersecretion, respectively. However, these biotherapeutics can be difficult and expensive to manufacture with multiple challenges from recombinant protein generation through to the development of long-acting formulations required to improve the circulating half-life of the drug. In this review, we summarize methodologies and approaches used for making and purifying recombinant GH and GHA proteins, and strategies to improve pharmacokinetic and pharmacodynamic properties, including PEGylation and fusion proteins. Therapeutics that are in clinical use or are currently under development are also discussed.
Topics: Humans; Human Growth Hormone; Recombinant Proteins; Receptors, Somatotropin
PubMed: 37428391
DOI: 10.1002/pro.4727 -
Nature Reviews. Endocrinology Sep 2022Since its discovery nearly a century ago, over 100,000 studies of growth hormone (GH) have investigated its structure, how it interacts with the GH receptor and its... (Review)
Review
Since its discovery nearly a century ago, over 100,000 studies of growth hormone (GH) have investigated its structure, how it interacts with the GH receptor and its multiple actions. These include effects on growth, substrate metabolism, body composition, bone mineral density, the cardiovascular system and brain function, among many others. Recombinant human GH is approved for use to promote growth in children with GH deficiency (GHD), along with several additional clinical indications. Studies of humans and animals with altered levels of GH, from complete or partial GHD to GH excess, have revealed several covert or hidden actions of GH, such as effects on fibrosis, cardiovascular function and cancer. In this Review, we do not concentrate on the classic and controversial indications for GH therapy, nor do we cover all covert actions of GH. Instead, we stress the importance of the relationship between GH and fibrosis, and how fibrosis (or lack thereof) might be an emerging factor in both cardiovascular and cancer pathologies. We highlight clinical data from patients with acromegaly or GHD, alongside data from cellular and animal studies, to reveal novel phenotypes and molecular pathways responsible for these actions of GH in fibrosis, cardiovascular function and cancer.
Topics: Animals; Cardiovascular Diseases; Child; Dwarfism, Pituitary; Fibrosis; Growth Hormone; Human Growth Hormone; Humans; Neoplasms
PubMed: 35750929
DOI: 10.1038/s41574-022-00702-6 -
Best Practice & Research. Clinical... Feb 2017Growth hormone (GH) replacement therapy in adults with GH deficiency is still a challenge for the clinical endocrinologist and its implementation has still numerous... (Review)
Review
Growth hormone (GH) replacement therapy in adults with GH deficiency is still a challenge for the clinical endocrinologist and its implementation has still numerous difficulties and uncertainties. The decision to treat GH deficient adults requires a thoughtful and individualized evaluation of risks and benefits. Benefits have been found in body composition, bone health, cardiovascular risk factors, and quality of life. However, evidences for a reduction in cardiovascular events and mortality are still lacking, and treatment costs remain high. It is advisable to start treatment with low doses of GH, the goals being an appropriate clinical response, an avoidance of side effects, and IGF-I levels in the age-adjusted reference range. Although treatment appears to be overall safe, certain areas continue to require long-term surveillance, such as risks of glucose intolerance, pituitary/hypothalamic tumor recurrence, and cancer.
Topics: Adult; Body Composition; Bone and Bones; Cardiovascular Diseases; Glucose Intolerance; Hormone Replacement Therapy; Human Growth Hormone; Humans; Hypopituitarism; Insulin-Like Growth Factor I; Male; Middle Aged; Neoplasm Recurrence, Local; Quality of Life; Reference Values; Risk Factors
PubMed: 28477728
DOI: 10.1016/j.beem.2017.03.001 -
Growth Hormone & IGF Research :... 2023Patients with Noonan syndrome typically have a target height <2 standard deviations compared to the general population, and half of the affected adults remain... (Review)
Review
Patients with Noonan syndrome typically have a target height <2 standard deviations compared to the general population, and half of the affected adults remain permanently below the 3rd centile for height, though their short stature might result from a multifactorial etiology, not-yet fully understood. The secretion of growth hormone (GH) following the classic GH stimulation tests is often normal, with baseline insulin-like growth factor-1 (IGF-1) levels at the lower normal limits, but patients with Noonan syndrome have also a possible moderate response to GH therapy, leading to a final increased height and substantial improvement in growth rate. Aim of this review was to evaluate both safety and efficacy of GH therapy in children and adolescents with Noonan syndrome, also evaluating as a secondary aim the possible correlations between the underlying genetic mutations and GH responses.
Topics: Adolescent; Humans; Child; Growth Hormone; Noonan Syndrome; Human Growth Hormone; Insulin-Like Growth Factor I; Growth Disorders; Mutation; Body Height
PubMed: 37084633
DOI: 10.1016/j.ghir.2023.101532 -
Frontiers in Endocrinology 2021Daily recombinant human GH (rhGH) is currently approved for use in children and adults with GH deficiency (GHD) in many countries with relatively few side-effects.... (Review)
Review
Daily recombinant human GH (rhGH) is currently approved for use in children and adults with GH deficiency (GHD) in many countries with relatively few side-effects. Nevertheless, daily injections can be painful and distressing for some patients, often resulting in non-adherence and reduction of treatment outcomes. This has prompted the development of numerous long-acting GH (LAGH) analogs that allow for decreased injection frequency, ranging from weekly, bi-weekly to monthly. These LAGH analogs are attractive as they may theoretically offer increased patient acceptance, tolerability, and therapeutic flexibility. Conversely, there may also be pitfalls to these LAGH analogs, including an unphysiological GH profile and differing molecular structures that pose potential clinical issues in terms of dose initiation, therapeutic monitoring, incidence and duration of side-effects, and long-term safety. Furthermore, fluctuations of peak and trough serum GH and IGF-I levels and variations in therapeutic efficacy may depend on the technology used to prolong GH action. Previous studies of some LAGH analogs have demonstrated non-inferiority compared to daily rhGH in terms of increased growth velocity and improved body composition in children and adults with GHD, respectively, with no significant unanticipated adverse events. Currently, two LAGH analogs are marketed in Asia, one recently approved in the United States, another previously approved but not marketed in Europe, and several others proceeding through various stages of clinical development. Nevertheless, several practical questions still remain, including possible differences in dose initiation between naïve and switch-over patients, methodology of dose adjustment/s, timing of measuring serum IGF-I levels, safety, durability of efficacy and cost-effectiveness. Long-term surveillance of safety and efficacy of LAGH analogs are needed to answer these important questions.
Topics: Body Composition; Dwarfism, Pituitary; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Patient Compliance; Patient Safety; Protein Transport; Recombinant Proteins; Signal Transduction; Treatment Outcome
PubMed: 33716988
DOI: 10.3389/fendo.2021.637209 -
International Journal of Molecular... Jun 2023Congenital growth hormone deficiency (GHD) is a rare disease caused by disorders affecting the morphogenesis and function of the pituitary gland. It is sometimes found... (Review)
Review
Congenital growth hormone deficiency (GHD) is a rare disease caused by disorders affecting the morphogenesis and function of the pituitary gland. It is sometimes found in isolation but is more frequently associated with multiple pituitary hormone deficiency. In some cases, GHD may have a genetic basis. The many clinical signs and symptoms include hypoglycaemia, neonatal cholestasis and micropenis. Diagnosis should be made by laboratory analyses of the growth hormone and other pituitary hormones, rather than by cranial imaging with magnetic resonance imaging. When diagnosis is confirmed, hormone replacement should be initiated. Early GH replacement therapy leads to more positive outcomes, including reduced hypoglycaemia, growth recovery, metabolic asset, and neurodevelopmental improvements.
Topics: Infant, Newborn; Humans; Hypopituitarism; Human Growth Hormone; Pituitary Hormones; Growth Hormone; Hypoglycemia
PubMed: 37373261
DOI: 10.3390/ijms241210114