-
American Journal of Orthodontics and... Mar 2018
Topics: Growth Hormone; Human Growth Hormone
PubMed: 29501103
DOI: 10.1016/j.ajodo.2017.11.022 -
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 -
Journal of Neuroendocrinology Nov 2020
Topics: Animals; Growth Hormone; Human Growth Hormone; Humans; Mice; Prolactin
PubMed: 33128814
DOI: 10.1111/jne.12909 -
Aging Aug 2019
Topics: Gene Expression Profiling; Human Growth Hormone; Humans; MicroRNAs; Multigene Family; Signal Transduction
PubMed: 31389342
DOI: 10.18632/aging.102145 -
Best Practice & Research. Clinical... Feb 2017The interrelationships of growth hormone (GH) actions and aging are complex and incompletely understood. The very pronounced age-related decline in GH secretion together... (Review)
Review
The interrelationships of growth hormone (GH) actions and aging are complex and incompletely understood. The very pronounced age-related decline in GH secretion together with benefits of GH therapy in individuals with congenital or adult GH deficiency (GHD) prompted interest in GH as an anti-aging agent. However, the benefits of treatment of normal elderly subjects with GH appear to be marginal and counterbalanced by worrisome side effects. In laboratory mice, genetic GH deficiency or resistance leads to a remarkable extension of longevity accompanied by signs of delayed and/or slower aging. Mechanisms believed to contribute to extended longevity of GH-related mutants include improved anti-oxidant defenses, enhanced insulin sensitivity and reduced insulin levels, reduced inflammation and cell senescence, major shifts in mitochondrial function and energy metabolism, and greater stress resistance. Negative association of the somatotropic signaling and GH/insulin-like growth factor 1 (IGF-1)-dependent traits with longevity has also been shown in other mammalian species. In humans, syndromes of GH resistance or deficiency have no consistent effect on longevity, but can provide striking protection from cancer, diabetes and atherosclerosis. More subtle alterations in various steps of GH and IGF-1 signaling are associated with reduced old-age mortality, particularly in women and with improved chances of attaining extremes of lifespan. Epidemiological studies raise a possibility that the relationship of IGF-1 and perhaps also GH levels with human healthy aging and longevity may be biphasic. However, the impact of somatotropic signaling on neoplastic disease is difficult to separate from its impact on aging, and IGF-1 levels exhibit opposite associations with different chronic, age-related diseases.
Topics: Aging; Animals; Energy Metabolism; Human Growth Hormone; Humans; Hypopituitarism; Inflammation; Insulin-Like Growth Factor I; Longevity; Mice, Transgenic; Neoplasms; Phenotype; Signal Transduction
PubMed: 28477727
DOI: 10.1016/j.beem.2017.02.005 -
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 :... Feb 2018Along with its inherent properties in growth promotion, cell division and regeneration, growth hormone (GH) exerts a variety of miscellaneous and widespread actions on... (Review)
Review
Along with its inherent properties in growth promotion, cell division and regeneration, growth hormone (GH) exerts a variety of miscellaneous and widespread actions on the human body after binding to its receptor (GHR). Indeed, GH influences the metabolism of carbohydrates, lipids and proteins; shapes body composition, influences cardiovascular profile, quality of life, and induces other direct and indirect physiologic effects. Besides this salutary actions, GH and its derived peptide insulin-like growth factor-I (IGF-I), main product of the GH/GHR interaction, have been implicated in the genesis of diseases such as cancer and insulin-resistant diabetes. The effects of these peptides are difficult to discern in healthy individuals but can be better evaluated in disease states in which their action in target tissues is abnormal. In consequence, we selected acromegaly and Laron syndrome due to GH receptor deficiency (GHRD) as models for excess and absence of GH action, and focused in the role of GH/GHR signaling in the genesis of cancer and diabetes. Considering that malignancy has been linked at epidemiological level to type 2 diabetes and high body mass index, suggesting that hyperinsulinemia is an independent contributor to cancer genesis and progression, we propose that the GH-derived IGF-I is also an independent influence for progression to neoplasia since its absence associates with less DNA damage, diminished mutagenesis and efficient apoptosis. Regarding development of type 2 diabetes, we support the notion that GH, by influencing insulin sensitivity via its counter-regulatory properties on carbohydrate metabolism, is an important contributor for development of this disease.
Topics: Diabetes Mellitus; Human Growth Hormone; Humans; Insulin Resistance; Neoplasms; Receptors, Somatotropin; Signal Transduction
PubMed: 29395968
DOI: 10.1016/j.ghir.2017.12.006 -
Hormone Research in Paediatrics 2022People have long been fascinated with the size and growth of living things, from the giants of classic mythology and art to the little people who also have appeared in... (Review)
Review
BACKGROUND
People have long been fascinated with the size and growth of living things, from the giants of classic mythology and art to the little people who also have appeared in classical art, as well as the courts of European monarchs, and were exploited in "shows." Serious medical evaluation began in the late 19th century with the description of acromegaly and its association with pituitary tumors. In the early 20th century, multiple investigators attempted to extract a growth-promoting factor from the anterior pituitary and then, over the decades, to purify it and distinguish it from other anterior pituitary hormones. With relatively pure growth hormone (GH), its biological activity in growth promotion and as a metabolic hormone were studied, and species specificity became apparent: primate GH was the only GH active in man. Human GH was prepared from cadaveric pituitaries and distributed by the NIH to treat children with GH deficiency, but there was never enough pituitary hGH for all of the children who required it. When Creutzfeldt-Jakob disease was found in some patients who received pituitary GH, the production and FDA approval of biosynthetic hGH dramatically accelerated. With a large supply, one could treat those who were GH deficient and test its efficacy in other causes of short stature; longer acting versions of hGH have now been developed, tested, and in a few instances received FDA approval.
SUMMARY
It has been a long journey from the description of over- and underproduction of GH in animals to the production and clinical use of the biosynthetic hormones.
KEY MESSAGES
The efforts of basic scientists led to the extraction and purification of GH. Clinical scientists have expanded the appropriate use of hGH for short children with conditions in addition to GH deficiency.
Topics: Animals; Humans; Acromegaly; Dwarfism; Endocrine System Diseases; Growth Hormone; Human Growth Hormone; Pituitary Hormones, Anterior
PubMed: 36446319
DOI: 10.1159/000526440 -
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 -
Growth Hormone & IGF Research :... Jun 2016Growth is a good indicator of a child's health. Growth disturbances, including short stature or growth failure, could be indications of illnesses such as chronic... (Review)
Review
Growth is a good indicator of a child's health. Growth disturbances, including short stature or growth failure, could be indications of illnesses such as chronic disease, nutritional deficits, celiac disease or hormonal abnormalities. Therefore, a careful assessment of the various requirements for normal growth needs to be done by history, physical examination, and screening laboratory tests. More details will be reviewed about the GH-IGF axis, its abnormalities with special emphasis on GH deficiency, its diagnosis and treatment. GH treatment indications in the US will be reviewed and a few only will be highlighted. They will include GH deficiency, as well as the treatment of children born SGA, including the results of a US study using FDA approved dose of 0.48mg/kg/week. GH deficiency in adults will also be briefly reviewed. Treatment of patients with SHOX deficiency will also be discussed. Possible side effects of GH treatment and the importance of monitoring safety will be highlighted.
Topics: Growth Disorders; Human Growth Hormone; Humans; Infant, Small for Gestational Age; Insulin-Like Growth Factor I; Short Stature Homeobox Protein; Turner Syndrome
PubMed: 26936284
DOI: 10.1016/j.ghir.2016.02.004