-
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 -
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 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 -
Archives of Endocrinology and Metabolism 2019The somatotropic axis is the main hormonal regulator of growth. Growth hormone (GH), also known as somatotropin, and insulin-like growth factor 1 (IGF-1) are the key... (Review)
Review
The somatotropic axis is the main hormonal regulator of growth. Growth hormone (GH), also known as somatotropin, and insulin-like growth factor 1 (IGF-1) are the key components of the somatotropic axis. This axis has been studied for a long time and the knowledge of how some molecules could promote or impair hormones production and action has been growing over the last decade. The enhancement of large-scale sequencing techniques has expanded the spectrum of known genes and several other candidate genes that could affect the GH-IGF1-bone pathway. To date, defects in more than forty genes were associated with an impairment of the somatotropic axis. These defects can affect from the secretion of GH to the bioavailability and action of IGF-1. Affected patients present a large heterogeneous group of conditions associated with growth retardation. In this review, we focus on the description of the GH-IGF axis genetic defects reported in the last decade. Arch Endocrinol Metab. 2019;63(6):608-17.
Topics: Genotype; Growth Disorders; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Mutation; Phenotype; Signal Transduction
PubMed: 31939486
DOI: 10.20945/2359-3997000000191 -
Frontiers in Endocrinology 2024
Topics: Humans; Dwarfism; Human Growth Hormone
PubMed: 38606084
DOI: 10.3389/fendo.2024.1403112 -
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 -
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 -
Molecular and Cellular Endocrinology Dec 2020Growth hormone (GH) is a pleiotropic hormone that coordinates an array of physiological processes, including effects on bone, muscle, and fat, ultimately resulting in... (Review)
Review
Growth hormone (GH) is a pleiotropic hormone that coordinates an array of physiological processes, including effects on bone, muscle, and fat, ultimately resulting in growth. Metabolically, GH promotes anabolic action in most tissues except adipose, where its catabolic action causes the breakdown of stored triglycerides into free fatty acids (FFA). GH antagonizes insulin action via various molecular pathways. Chronic GH secretion suppresses the anti-lipolytic action of insulin and increases FFA flux into the systemic circulation; thus, promoting lipotoxicity, which causes pathophysiological problems, including insulin resistance. In this review, we will provide an update on GH-stimulated adipose lipolysis and its consequences on insulin signaling in liver, skeletal muscle, and adipose tissue. Furthermore, we will discuss the mechanisms that contribute to the diabetogenic action of GH.
Topics: Adipose Tissue; Animals; Diabetes Mellitus; Growth Hormone; Human Growth Hormone; Humans; Insulin; Insulin Resistance; Lipolysis; Signal Transduction
PubMed: 32966863
DOI: 10.1016/j.mce.2020.111038