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Frontiers in Endocrinology 2021Growth hormone (GH), once the age of linear growth is completed, continues to play a fundamental role for the human body. In adulthood, GH contributes to regulate... (Review)
Review
Growth hormone (GH), once the age of linear growth is completed, continues to play a fundamental role for the human body. In adulthood, GH contributes to regulate muscle, cardiovascular and bone metabolism. The same happens in old age, although there is less data on the effect of GH in the elderly. Regardless the age of onset, a reduced quality of life (QoL), an increased cardiovascular risk and an accelerated age-related decline in physical strength have been demonstrated in the elderly with GH deficiency (EGHD). In adults with GH deficiency (AGHD), recent studies suggest a role of GH replacement therapy (GHrt) in improving lean/fat mass ratio, blood pressure, lipid profile, bone metabolism and QoL. Despite these recent studies, there is still a lack of randomized controlled trials proving these positive effects in EGHD. Moreover, the lack of a long-term positive outcome on mortality, and the cost of GHrt could often impact on treatment decision-making and lead to postpone or avoid the prescription. The aim of this mini-review is to summarize the available data on GHrt in EGHD, in order to highlight its weaknesses and strengths and to provide directions to clinicians that will help in the management of this specific set of patients.
Topics: Aged; Body Composition; Cognition; Hormone Replacement Therapy; Human Growth Hormone; Humans; Muscle Strength; Quality of Life
PubMed: 34211437
DOI: 10.3389/fendo.2021.680579 -
Genetics in Medicine : Official Journal... 2002The technologies made available by new research in genetics and genomics have been and will be used not only to diagnose and treat disease, but also to attempt to... (Review)
Review
The technologies made available by new research in genetics and genomics have been and will be used not only to diagnose and treat disease, but also to attempt to enhance human traits and capacities. A broad definition of genetic-enhancement technologies, not merely gene manipulation, but also indirect genetic technologies, such as biosynthetic drugs, is needed to capture the full range of possible applications. It is difficult, but often possible, to anticipate the enhancement temptations of new therapies. Such anticipation may help us in shaping the marketing, availability, or other aspects of those technologies. Appropriate public and professional policies are needed, and work on them should begin immediately. Most important, we must stimulate public education and dialogue to encourage personal ethical reflection on the appropriate uses and limits of genetic-enhancement technologies.
Topics: Body Height; Cloning, Organism; Doping in Sports; Genetic Enhancement; Human Growth Hormone; Humans
PubMed: 12544484
DOI: 10.1097/00125817-200211001-00006 -
Archives of Endocrinology and Metabolism 2019Skeletal muscle is a target tissue of GH. Based on its anabolic properties, it is widely accepted that GH enhances muscle performance in sports. Athletic performance... (Review)
Review
Skeletal muscle is a target tissue of GH. Based on its anabolic properties, it is widely accepted that GH enhances muscle performance in sports. Athletic performance depends on muscle strength and the energy required to power muscle function. The energy required to power muscle function is derived from a continuum of anaerobic and aerobic sources. Molecular and functional studies provide evidence that in muscle GH stimulates the anaerobic and suppresses the aerobic energy system, in turn affecting power-based functional measures in a time-dependent manner. In recreational athletes, GH improves anaerobic capacity but has not been proven to significantly enhance muscle strength, power, or maximum rate of oxygen consumption. GH appears likely to selectively benefit sprint events and not physical performance that depends on strength and endurance. Arch Endocrinol Metab. 2019;63(6):576-81.
Topics: Athletes; Human Growth Hormone; Humans; Muscle Strength; Muscle, Skeletal; Oxygen Consumption
PubMed: 31939482
DOI: 10.20945/2359-3997000000187 -
Archives of Endocrinology and Metabolism 2019Growth hormone therapy with daily injections of recombinant human growth hormone has been available since 1985, and is shown to be safe and effective treatment for short... (Review)
Review
Growth hormone therapy with daily injections of recombinant human growth hormone has been available since 1985, and is shown to be safe and effective treatment for short stature in children and for adult growth hormone deficiency. In an effort to produce a product that would improve patient adherence, there has been a strong effort from industry to create a long acting form of growth hormone to ease the burden of use. Technologies used to increase half-life include depot formulations, PEGylated formulations, pro-drug formulations, non-covalent albumin binding growth hormone and growth hormone fusion proteins. At present, two long acting formulations are on the market in China and South Korea, and several more promising agents are under clinical investigation at various stages of development throughout the world. Arch Endocrinol Metab. 2019;63(6):601-7.
Topics: Adult; Chemistry, Pharmaceutical; Child; Delayed-Action Preparations; Drug Administration Schedule; Drug Design; Growth Disorders; Human Growth Hormone; Humans
PubMed: 31939485
DOI: 10.20945/2359-3997000000190 -
Archives of Endocrinology and Metabolism 2019Growth hormone (GH) deficiency (GHD) in adults is well-characterized and includes abnormal body composition, reduced bone mass, an adverse cardiovascular risk profile,... (Review)
Review
Growth hormone (GH) deficiency (GHD) in adults is well-characterized and includes abnormal body composition, reduced bone mass, an adverse cardiovascular risk profile, and impaired quality of life. In the early 1990s, it was also shown that patients with hypopituitarism without GH replacement therapy (GHRT) had excess mortality. Today, GHRT has been shown to decrease or reverse the negative effects of GHD. In addition, recent papers have shown that mortality and morbidity are approaching normal in hypopituitary patients with GHD who receive modern endocrine therapy including GHRT. Since the first dose-finding studies, it has been clear that efficacy and side effects differ substantially between patients. Many factors have been suggested as affecting responsiveness, such as sex, age, age at GHD onset, adherence, and GH receptor polymorphisms, with sex and sex steroid replacement having the greatest impact. Therefore, the individual tailoring of GH dose is of great importance to achieve sufficient efficacy without side effects. One group that stands out is women receiving oral estrogen replacement, who needs the highest dose. Serum insulin-like growth factor-1 (IGF-1) is still the most used biochemical biomarker for GH dose titration, although the best serum IGF-1 target is still debated. Patients with GHD due to acromegaly, Cushing's disease, or craniopharyngioma experience similar effects from GHRT as others. Arch Endocrinol Metab. 2019;63(6):592-600.
Topics: Adult; Age of Onset; Female; Hormone Replacement Therapy; Human Growth Hormone; Humans; Male; Medication Adherence; Precision Medicine; Quality of Life
PubMed: 31939484
DOI: 10.20945/2359-3997000000189 -
Physiological Reviews Apr 1999The secretion of growth hormone (GH) is regulated through a complex neuroendocrine control system, especially by the functional interplay of two hypothalamic... (Review)
Review
The secretion of growth hormone (GH) is regulated through a complex neuroendocrine control system, especially by the functional interplay of two hypothalamic hypophysiotropic hormones, GH-releasing hormone (GHRH) and somatostatin (SS), exerting stimulatory and inhibitory influences, respectively, on the somatotrope. The two hypothalamic neurohormones are subject to modulation by a host of neurotransmitters, especially the noradrenergic and cholinergic ones and other hypothalamic neuropeptides, and are the final mediators of metabolic, endocrine, neural, and immune influences for the secretion of GH. Since the identification of the GHRH peptide, recombinant DNA procedures have been used to characterize the corresponding cDNA and to clone GHRH receptor isoforms in rodent and human pituitaries. Parallel to research into the effects of SS and its analogs on endocrine and exocrine secretions, investigations into their mechanism of action have led to the discovery of five separate SS receptor genes encoding a family of G protein-coupled SS receptors, which are widely expressed in the pituitary, brain, and the periphery, and to the synthesis of analogs with subtype specificity. Better understanding of the function of GHRH, SS, and their receptors and, hence, of neural regulation of GH secretion in health and disease has been achieved with the discovery of a new class of fairly specific, orally active, small peptides and their congeners, the GH-releasing peptides, acting on specific, ubiquitous seven-transmembrane domain receptors, whose natural ligands are not yet known.
Topics: Amino Acid Sequence; Brain Chemistry; Female; Human Growth Hormone; Humans; Male; Molecular Sequence Data; Neurosecretory Systems; Neurotransmitter Agents
PubMed: 10221989
DOI: 10.1152/physrev.1999.79.2.511 -
International Journal of Molecular... Jul 2017Obesity is an excessive accumulation or expansion of adipose tissue (AT) due to an increase in either the size and/or number of its characteristic cell type, the... (Review)
Review
Obesity is an excessive accumulation or expansion of adipose tissue (AT) due to an increase in either the size and/or number of its characteristic cell type, the adipocyte. As one of the most significant public health problems of our time, obesity and its associated metabolic complications have demanded that attention be given to finding effective therapeutic options aimed at reducing adiposity or the metabolic dysfunction associated with its accumulation. Growth hormone (GH) has therapeutic potential due to its potent lipolytic effect and resultant ability to reduce AT mass while preserving lean body mass. However, AT and its resident adipocytes are significantly more dynamic and elaborate than once thought and require one not to use the reduction in absolute mass as a readout of efficacy alone. Paradoxically, therapies that reduce GH action may ultimately prove to be healthier, in part because GH also possesses potent anti-insulin activities along with concerns that GH may promote the growth of certain cancers. This review will briefly summarize some of the newer complexities of AT relevant to GH action and describe the current understanding of how GH influences this tissue using data from both humans and mice. We will conclude by considering the therapeutic use of GH or GH antagonists in obesity, as well as important gaps in knowledge regarding GH and AT.
Topics: Adipocytes; Adipose Tissue; Animals; Human Growth Hormone; Humans; Mice; Obesity; Receptors, Somatotropin
PubMed: 28933734
DOI: 10.3390/ijms18081621 -
Genomics Jan 2020Personalized medicine, one of the main promises of the Human Genome Project (HGP) that began three decades ago, is now a new therapeutic paradigm. With its arrival the... (Review)
Review
Personalized medicine, one of the main promises of the Human Genome Project (HGP) that began three decades ago, is now a new therapeutic paradigm. With its arrival the era of developing drugs to suit all patients, yet often having to withdraw a promising new one because a minority of patients was at risk, even though it had proved valuable for the majority was consigned to history as were trial-and-error strategies being the predominant means of tailoring therapy. But how did it originate and the earliest examples emerge? Is it true that the first personalized diagnostic test was the companion test for Herceptin®? This account of a remarkable journey from genomic and translational research to therapeutic and diagnostic innovations, describes how sequencing the human growth hormone (hGH) locus provided proof of principle for HGP-inspired personalized medicine. Sequencing this locus and the resultant biomanufacture of HGH and the development of a test capable of detecting which patients would benefit from its administration helped silence the skeptics who questioned the validity of such an approach. The associated companion diagnostic was created four years before the invention of the HercepTest® (registered as the first companion diagnostics ever developed). By cultivating genomic research with passion and pursuing its applications, we and many others contributed to the emergence of a new diagnostics industry, the discovery of better actionable gene-targets and to a revitalized pharmaceutical industry capable of developing safer and more effective therapies. In combination, these developments are beginning to fulfill the promise of the HGP, offering each patient the opportunity to adopt the right treatment at the correct dosage in an opportune manner.
Topics: Genetic Loci; Genomics; Human Growth Hormone; Humans; Precision Medicine; Proof of Concept Study
PubMed: 31078717
DOI: 10.1016/j.ygeno.2019.05.006 -
Frontiers in Endocrinology 2023Linear growth during childhood is the result of the synergic contribution of different factors. The best growth determinant system during each period of life is... (Review)
Review
Linear growth during childhood is the result of the synergic contribution of different factors. The best growth determinant system during each period of life is represented by the growth hormone-insulin-like growth factor axis (GH-IGF), even if several other factors are involved in normal growth. Within the broad spectrum of growth disorders, an increased importance has been placed on growth hormone insensitivity (GHI). GHI was reported for the first time by Laron as a syndrome characterized by short stature due to GH receptor (GHR) mutation. To date, it is recognized that GHI represents a wide diagnostic category, including a broad spectrum of defects. The peculiar characteristic of GHI is the low IGF-1 levels associated with normal or elevated GH levels and the lack of IGF-1 response after GH administration. Recombinant IGF-1 preparations may be used in the treatment of these patients.
Topics: Dwarfism; Human Growth Hormone; Insulin-Like Growth Factor I; Humans; Growth Disorders
PubMed: 37008935
DOI: 10.3389/fendo.2023.1141039 -
Value in Health : the Journal of the... Jul 2018Acromegaly results from the hypersecretion of growth hormone. Because of the low incidence rates of this disease worldwide, few clinical trials evaluating drug... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acromegaly results from the hypersecretion of growth hormone. Because of the low incidence rates of this disease worldwide, few clinical trials evaluating drug treatments have been conducted.
OBJECTIVES
To conduct the first network meta-analysis simultaneously comparing all available drugs used in acromegaly treatment so as to provide more robust evidence in this field.
METHODS
A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane Collaboration recommendations (PROSPERO database under the registration number CRD42017059880). The electronic searches were conducted in PubMed (MEDLINE), Scopus, and Web of Science databases. Randomized controlled trials comparing any drug for the treatment of acromegaly head-to-head or versus placebo were included. Outcomes concerning the efficacy and safety of treatments were evaluated. The statistical analyses were performed using Aggregate Data Drug Information System version 1.16.8 (drugis.org, Groningen, The Netherlands).
RESULTS
The initial search retrieved 2059 articles. Of these, 10 randomized controlled trials were included in a qualitative analysis and 7 in a quantitative analysis. The network meta-analysis for the efficacy outcome (number of patients achieving insulinlike growth factor 1 control) showed that pegvisomant and lanreotide autogel were statistically superior to placebo (odds ratio [95% credible interval] 0.06 [0.00-0.55] and 0.09 [0.01-0.88]). No further differences were found. The probability rank indicated that pegvisomant and pasireotide have the highest probabilities (33% and 34%, respectively) of being the best therapeutic options. No major side effects were noted.
CONCLUSIONS
Pegvisomant is still a good option for acromegaly treatment, but pasireotide seems to be a promising alternative. Nevertheless, other important key factors such as drug costs and effectiveness (real-world results) should be taken into account when selecting acromegaly treatment.
Topics: Acromegaly; Adolescent; Adult; Aged; Aged, 80 and over; Female; Hormone Antagonists; Human Growth Hormone; Humans; Male; Middle Aged; Peptides, Cyclic; Receptors, Somatotropin; Somatostatin; Treatment Outcome; Young Adult
PubMed: 30005760
DOI: 10.1016/j.jval.2017.12.014