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Reviews in Endocrine & Metabolic... Mar 2021Growth hormone (GH) induces pleiotropic effects on growth and metabolism via binding and subsequent activation of the growth hormone receptor (GHR) and its downstream... (Review)
Review
Growth hormone (GH) induces pleiotropic effects on growth and metabolism via binding and subsequent activation of the growth hormone receptor (GHR) and its downstream signaling pathways. Growth hormone insensitivity (GHI) describes a group of disorders in which there is resistance to the action of GH and resultant insulin-like growth factor I (IGF-I) deficiency. GHI is commonly due to genetic disorders of the GH receptor causing GH receptor deficiency (e.g. Laron Syndrome (LS)), decreased activation of GHR, or defects in post-receptor signaling molecules. Genetically altered mouse lines have been invaluable to better understand the physiological impact of GHI due to the ability to do invasive and longitudinal measures of metabolism, growth, and health on a whole animal or in individual tissues/cells. In the current review, the phenotype of mouse lines with GHI will be reviewed. Mouse lines to be discussed include: 1) GHR-/- mice with a gene disruption in the GHR that results in no functional GHR throughout life, also referred to as the Laron mouse, 2) mice with temporal loss of GHR (aGHRKO) starting at 6 weeks of age, 3) mice transgenic for a GHR antagonist (GHA mice), 4) mice with GHI in select tissues or cells generated via Cre-lox or related technology, and 5) assorted mice with defects in post-receptor signaling molecules. Collectively, these mouse lines have revealed an intriguing role of GH action in health, disease, and aging.
Topics: Animals; Growth Disorders; Growth Hormone; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Laron Syndrome; Mice; Receptors, Somatotropin
PubMed: 33037595
DOI: 10.1007/s11154-020-09600-6 -
Frontiers in Endocrinology 2022In contemporary ART, the use of "add-ons" during ovarian stimulation has increased, especially in poor responders. Growth Hormone (GH) is an adjunctive therapy that has... (Review)
Review
In contemporary ART, the use of "add-ons" during ovarian stimulation has increased, especially in poor responders. Growth Hormone (GH) is an adjunctive therapy that has been studied extensively in the translational and clinical setting, with an ongoing scientific debate over its effectiveness and optimal use. In this review, we aim to provide an overview of the physiologic basis for the use of GH in ART, and to summarize the latest evidence regarding its clinical use, primarily as an adjunct to ovarian stimulation, but also in the IVF lab and with regards to its effects on the endometrium.
Topics: Female; Humans; Growth Hormone; Fertilization in Vitro; Ovulation Induction; Human Growth Hormone; Reproduction
PubMed: 36531455
DOI: 10.3389/fendo.2022.1055097 -
Molecular and Cellular Endocrinology Dec 2020In this review, I summarize historical and recent features of the classical pathways activated by growth hormone (GH) through the cell surface GH receptor (GHR). GHR is... (Review)
Review
In this review, I summarize historical and recent features of the classical pathways activated by growth hormone (GH) through the cell surface GH receptor (GHR). GHR is a cytokine receptor superfamily member that signals by activating the non-receptor tyrosine kinase, JAK2, and members of the Src family kinases. Activation of the GHR engages STATs, PI3K, and ERK pathways, among others, and details of these now-classical pathways are presented. Modulating elements, including the SOCS proteins, phosphatases, and regulated GHR metalloproteolysis, are discussed. In addition, a novel physical and functional interaction of GHR with IGF-1R is summarized and discussed in terms of its mechanisms, consequences, and physiological and therapeutic implications.
Topics: Animals; Growth Hormone; Human Growth Hormone; Humans; Receptors, Somatotropin; Signal Transduction
PubMed: 32835785
DOI: 10.1016/j.mce.2020.110999 -
Journal of Endocrinological... Jun 2017In 2007, we published an opinion document to review the role of pegvisomant (PEG) in the treatment of acromegaly. Since then, new evidence emerged on the biochemical and... (Review)
Review
BACKGROUND
In 2007, we published an opinion document to review the role of pegvisomant (PEG) in the treatment of acromegaly. Since then, new evidence emerged on the biochemical and clinical effects of PEG and on its long-term efficacy and safety.
AIM
We here reviewed the emerging aspects of the use of PEG in clinical practice in the light of the most recent literature.
RESULTS
The clinical use of PEG is still suboptimal, considering that it remains the most powerful tool to control IGF-I in acromegaly allowing to obtain, with a pharmacological treatment, the most important clinical effects in terms of signs and symptoms, quality of life and comorbidities. The number of patients with acromegaly exposed to PEG worldwide has become quite elevated and the prolonged follow-up allows now to deal quite satisfactorily with many clinical issues including major safety issues, such as the concerns about possible tumour (re)growth under PEG. The positive or neutral impact of PEG on glucose metabolism has been highlighted, and the clinical experience, although limited, with sleep apnoea and pregnancy has been reviewed. Finally, the current concept of somatostatin receptor ligands (SRL) resistance has been addressed, in order to better define the acromegaly patients to whom the PEG option may be offered.
CONCLUSIONS
PEG increasingly appears to be an effective and safe medical option for many patients not controlled by SRL but its use still needs to be optimized.
Topics: Acromegaly; Animals; Human Growth Hormone; Humans
PubMed: 28176221
DOI: 10.1007/s40618-017-0614-1 -
Neuroendocrinology 2016Historically, medical treatment of acromegaly has mainly been used as an adjuvant therapy after surgery. In the last decades, an increased range of medical therapy... (Review)
Review
Historically, medical treatment of acromegaly has mainly been used as an adjuvant therapy after surgery. In the last decades, an increased range of medical therapy options has been available. Somatostatin analogues have become the cornerstones of medical treatment in acromegaly and are even seen as a primary treatment in a selected group of acromegaly patients. The most recent medical treatment available for acromegaly patients is pegvisomant, a growth hormone receptor antagonist. To date, it is the most effective medical treatment, but it is costly. Pegvisomant is used as monotherapy and combined with somatostatin analogues. In this article, we review clinical studies and cohorts that have documented the efficacy of pegvisomant monotherapy and combined therapy and give a concise overview of associated side effects.
Topics: Acromegaly; Drug Therapy, Combination; Hormone Antagonists; Human Growth Hormone; Humans; Octreotide; Somatostatin
PubMed: 25792221
DOI: 10.1159/000381644 -
Current Diabetes Reports Oct 2022Canonical growth hormone (GH)-dependent signaling is essential for growth and counterregulatory responses to hypoglycemia, but also may contribute to glucose homeostasis... (Review)
Review
PURPOSE OF REVIEW
Canonical growth hormone (GH)-dependent signaling is essential for growth and counterregulatory responses to hypoglycemia, but also may contribute to glucose homeostasis (even in the absence of hypoglycemia) via its impact on metabolism of carbohydrates, lipids and proteins, body composition, and cardiovascular risk profile. The aim of this review is to summarize recent data implicating GH action in metabolic control, including both IGF-1-dependent and -independent pathways, and its potential role as target for T2D therapy.
RECENT FINDINGS
Experimental blockade of the GHR can modulate glucose metabolism. Moreover, the soluble form of the GH receptor (GHR, or GHBP) was recently identified as a mediator of improvement in glycemic control in patients with T2D randomized to bariatric surgery vs. medical therapy. Reductions in GHR were accompanied by increases in plasma GH, but unchanged levels of both total and free IGF-1. Likewise, hepatic GHR expression is reduced following both RYGB and VSG in rodents. Emerging data indicate that GH signaling is important for regulation of long-term glucose metabolism in T2D. Future studies will be required to dissect tissue-specific GH signaling and sensitivity and their contributions to systemic glucose metabolism.
Topics: Diabetes Mellitus, Type 2; Glucose; Growth Hormone; Human Growth Hormone; Humans; Hypoglycemia; Insulin-Like Growth Factor I; Randomized Controlled Trials as Topic
PubMed: 36001217
DOI: 10.1007/s11892-022-01488-7 -
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 -
Archives of Endocrinology and Metabolism 2019Tumor development is a multistep process whereby local mechanisms enable somatic mutations during preneoplastic stages. Once a tumor develops, it becomes a complex organ... (Review)
Review
Tumor development is a multistep process whereby local mechanisms enable somatic mutations during preneoplastic stages. Once a tumor develops, it becomes a complex organ composed of multiple cell types. Interactions between malignant and non-transformed cells and tissues create a tumor microenvironment (TME) comprising epithelial cancer cells, cancer stem cells, non-tumorous cells, stromal cells, immune-inflammatory cells, blood and lymphatic vascular network, and extracellular matrix. We review reports and present a hypothesis that postulates the involvement of growth hormone (GH) in field cancerization. We discuss GH contribution to TME, promoting epithelial-to-mesenchymal transition, accumulation of unrepaired DNA damage, tumor vascularity, and resistance to therapy. Arch Endocrinol Metab. 2019;63(6):568-75.
Topics: DNA Damage; Drug Resistance, Neoplasm; Epithelial-Mesenchymal Transition; Human Growth Hormone; Humans; Neovascularization, Pathologic; Tumor Microenvironment
PubMed: 31939481
DOI: 10.20945/2359-3997000000186 -
Frontiers in Endocrinology 2023The growth hormone (GH)-insulin-like growth factor-1 (IGF1) signaling pathway emerged in recent years as a key determinant of aging and longevity. Disruption of this... (Review)
Review
The growth hormone (GH)-insulin-like growth factor-1 (IGF1) signaling pathway emerged in recent years as a key determinant of aging and longevity. Disruption of this network in different animal species, including flies, nematodes and mouse, was consistently associated with an extended lifespan. Epidemiological analyses have shown that patients with Laron syndrome (LS), the best-characterized disease under the umbrella of the congenital IGF1 deficiencies, seem to be protected from cancer. While aging and cancer, as a rule, are considered diametrically opposite processes, modern lines of evidence reinforce the notion that aging and cancer might, as a matter of fact, be regarded as divergent manifestations of identical biochemical and cellular underlying processes. While the effect of individual mutations on lifespan and health span is very difficult to assess, genome-wide screenings identified a number of differentially represented aging- and longevity-associated genes in patients with LS. The present review summarizes recent data that emerged from comprehensive analyses of LS patients and portrays a number of previously unrecognized targets for GH-IGF1 action. Our article sheds light on complex aging and longevity processes, with a particular emphasis on the role of the GH-IGF1 network in these mechanisms.
Topics: Humans; Mice; Animals; Laron Syndrome; Aging; Longevity; Growth Hormone; Human Growth Hormone; Neoplasms
PubMed: 37941907
DOI: 10.3389/fendo.2023.1291812 -
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