Physiology, Growth Hormone - StatPearls - NCBI Bookshelf

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StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-.

StatPearls [Internet].

Show detailsTreasure Island (FL): StatPearls Publishing; 2025 Jan-.Search term Physiology, Growth Hormone

Joshua E. Brinkman; Muhammad Ali Tariq; Logan Leavitt; Sandeep Sharma.

Author Information and Affiliations

Authors

Joshua E. Brinkman1; Muhammad Ali Tariq2; Logan Leavitt3; Sandeep Sharma4.

Affiliations

1 DeBusk College of Osteopathic Medicine2 Tower Health3 Barrow Brain and Spine4 Mery Fitzgerald Hospital

Last Update: May 1, 2023.

Introduction

Human growth hormone (HGH), also known as somatotropin, is a 191-amino acid single-chain polypeptide produced by somatotropic cells within the anterior pituitary gland. As its name implies, scientists originally found that it is responsible for growth regulation during childhood. However, research has shown that HGH also regulates many of the body’s basal metabolic functions and acts as an acute-phase stress reactant.[1][2]

Cellular Level

Human growth hormone is produced by the anterior pituitary gland in acidophilic somatotrophic cells. Its production is tightly regulated by several complex feedback mechanisms in response to stress, exercise, nutrition, sleep, and growth hormone. The primary regulatory factors are growth hormone-releasing hormone (GHRH), produced in the hypothalamus; somatostatin, produced in various tissues throughout the body; and ghrelin, produced in the gastrointestinal tract. GHRH promotes HGH production and release. Somatostatin inhibits the release of GHRH and the HGH release response to GHRH stimulation and increases hypoglycemia. Ghrelin is a hormone produced by the stomach that plays a role in the hunger response. Functionally, the ghrelin response is protective against hypoglycemia. When elevated, ghrelin binds to somatotrophs to stimulate HGH secretion. Insulin-like growth factor-1 also inhibits HGH by directly inhibiting somatotrophic HGH release and indirectly increasing somatostatin release. Additionally, HGH will negatively feed back into the hypothalamus, thus decreasing GHRH production. The net effect of this regulatory mechanism produces a pulsatile release of HGH into circulation that varies hourly. In general, HGH levels increase in childhood, spike during puberty, and subsequently decrease with age.[3][4][5]

Function

HGH has two mechanisms of action: direct and indirect. The direct effects of HGH on the body occur through its binding to target cells, stimulating a response. The indirect effects occur primarily through insulin-like growth factor-1, which hepatocytes secrete in response to elevated HGH binding to surface receptors. Once activated, the Janus-activated tyrosine kinases (JAKs) 1 and 2 bind to the latent cytoplasmic transcription factors STAT1, STAT3, and STAT5, and transport them into the nucleus, inducing increased gene transcription and metabolism to produce insulin-like growth factor-1 for release into the circulation. Insulin-like growth factor-1 then affects the growth and metabolism of peripheral tissues. One can think of the effects of HGH as a combined effect of both HGH and insulin-like growth factor-1.

Growth

HGH induces growth in nearly every tissue and organ in the body. However, it is best known for its growth-promoting effects on cartilage and bone, especially during adolescence. Chondrocytes and osteoblasts receive signals to increase replication and thus allow for growth in size via HGH’s activation of the mitogen-activated protein (MAP) kinases designated ERKs (extracellular signal-regulated kinases) 1 and 2 cellular signaling pathways. Activation of this intracellular signaling cascade results in a cascade of protein activation, leading to increased gene transcription in the affected cells and ultimately to increased gene replication and cellular growth.

Insulin-like growth factor-1 binds to its receptor, IGF-1R, on the cell surface and activates a tyrosine kinase-mediated intracellular signaling pathway that phosphorylates various proteins, leading to increased metabolism, anabolism, and cellular replication and division. Furthermore, it inhibits cell apoptosis, thereby prolonging the lifespan of existing cells. The net result is to promote tissue growth and create a hyperglycemic environment in the body.

Metabolic Effects

HGH primarily affects metabolism by up-regulating insulin-like growth factor-1 production and its subsequent effects on peripheral cells. The intracellular signaling activation described above also significantly impacts the basal metabolic functions of organ tissues. In general, cells enter an anabolic state with increased amino acid uptake, increased protein synthesis, and decreased protein catabolism. Fats are processed and consumed by stimulating triglyceride breakdown and oxidation in adipocytes. Additionally, HGH suppresses insulin's ability to stimulate glucose uptake in peripheral tissues and increases hepatic gluconeogenesis, leading to an overall hyperglycemic state.[6][7][8]

Related Testing

Due to the pulsatile nature of HGH levels in the blood, conventional serum HGH measurements are almost useless because values can range from undetectable to extremely high, depending on environmental stressors and conditions. If a clinician suspects HGH deficiency, it is best to evaluate insulin-like growth factor I and insulin-like growth factor binding protein-3 levels and to perform HGH stimulation tests.

In an HGH stimulation test, the patient fasts overnight, and a pharmacological challenge is added in the morning with either L-DOPA, clonidine, propranolol, glucagon, arginine, or insulin-induced hypoglycemia. HGH serum levels are then evaluated hourly to assess the response to increased hormone levels. Failure of this test to increase HGH levels, therefore, indicates HGH deficiency.[9][10]

Clinical Significance

HGH is extremely important for modulating growth during adolescence. Therefore, major aberrations in HGH regulation may result in growth defects. HGH hypersecretion results in gigantism or acromegaly, whereas HGH deficiency results in a growth deficit in children and the GH deficiency syndrome in adults.

Acromegaly

Acromegaly typically results from an HGH-secreting pituitary adenoma with an onset after the closure of the epiphyseal growth plates, typically in adulthood. Therefore, bone growth primarily affects flat bones, such as the skull, mandible, sternum, and the hands and feet. Often, the presenting complaint is that hats or gloves no longer fit due to swelling of the hands and head. Because the illness is due to a pituitary mass, hypopituitarism may also develop with secondary reproductive disorders and visual symptoms. In addition to bony growth, myocardial growth occurs, resulting in biventricular concentric hypertrophy and subsequent heart failure in later disease. Because HGH counteracts insulin's effects on glucose and lipid metabolism, diabetes mellitus type 2 and hyperlipidemia are strongly associated with this disease. Treatment consists of surgery and radiation therapy targeting the underlying adenoma as well as symptomatic relief of the secondary effects of HGH as above.

Gigantism

This illness is very similar to acromegaly in all respects, except that the underlying pituitary adenoma develops before the closure of the long-bone epiphysis. Therefore, bone growth occurs in long bones such as the tibia, fibula, femur, humerus, radius, and ulna. Since epiphyseal closure occurs before adulthood, this is typically an illness with an onset seen in children. The organ and metabolic effects are similar to those of acromegaly.

HGH Deficiency

In children, idiopathic HGH deficiency is the most common. In adult-onset HGH deficiency, it typically presents as a constellation of hypopituitary deficiencies. The triggering incident is typically a pituitary adenoma, most likely a prolactinoma. However, other treatments, such as radiation therapy or surgery, might be the cause. Childhood-onset is associated with decreased growth of all skeletal structures, leading to dwarfism. Adult-onset HGH deficiency is less easily diagnosed because it lacks a single pathognomonic feature. Typically, adults have decreased skeletal muscle mass and increased visceral fat, as well as decreased bone density and remodeling, which can lead to osteoporosis. Dyslipidemia and insulin resistance are prevalent, which lead to secondary cardiovascular dysfunction, depressed mood, increased anxiety, and a lack of energy.[11][12][13]

Review Questions

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References

1.Baltaci AK, Mogulkoc R, Baltaci SB. Review: The role of zinc in the endocrine system. Pak J Pharm Sci. 2019 Jan;32(1):231-239. [PubMed: 30772815]2.Vanderkuur JA, Butch ER, Waters SB, Pessin JE, Guan KL, Carter-Su C. Signaling molecules involved in coupling growth hormone receptor to mitogen-activated protein kinase activation. Endocrinology. 1997 Oct;138(10):4301-7. [PubMed: 9322943]3.Binder G. Noonan syndrome, the Ras-MAPK signalling pathway and short stature. Horm Res. 2009 Apr;71 Suppl 2:64-70. [PubMed: 19407499]4.Al Aboud AM, Syed HA, Zito PM. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Feb 26, 2024. Alopecia. [PubMed: 30844205]5.Han Y, Leaman DW, Watling D, Rogers NC, Groner B, Kerr IM, Wood WI, Stark GR. Participation of JAK and STAT proteins in growth hormone-induced signaling. J Biol Chem. 1996 Mar 08;271(10):5947-52. [PubMed: 8621469]6.Ayuk J, Sheppard MC. Growth hormone and its disorders. Postgrad Med J. 2006 Jan;82(963):24-30. [PMC free article: PMC2563724] [PubMed: 16397076]7.Lanes R, Hurtado E. Oral clonidine-an effective growth hormone-releasing agent in prepubertal subjects. J Pediatr. 1982 May;100(5):710-4. [PubMed: 7040621]8.Stimulation of growth hormone secretion by levodopa-propranolol in children and adolescents. Pediatrics. 1975 Aug;56(2):262-6. [PubMed: 169508]9.Mitchell ML, Byrne MJ, Sanchez Y, Sawin CT. Detection of growth-hormone deficiency. N Engl J Med. 1970 Mar 05;282(10):539-41. [PubMed: 5413105]10.Mullis PE. Genetics of GHRH, GHRH-receptor, GH and GH-receptor: its impact on pharmacogenetics. Best Pract Res Clin Endocrinol Metab. 2011 Feb;25(1):25-41. [PubMed: 21396573]11.Gehmert S, Sadat S, Song YH, Yan Y, Alt E. The anti-apoptotic effect of IGF-1 on tissue resident stem cells is mediated via PI3-kinase dependent secreted frizzled related protein 2 (Sfrp2) release. Biochem Biophys Res Commun. 2008 Jul 11;371(4):752-5. [PubMed: 18466761]12.Merimee TJ, Rabinowtitz D, Fineberg SE. Arginine-initiated release of human growth hormone. Factors modifying the response in normal man. N Engl J Med. 1969 Jun 26;280(26):1434-8. [PubMed: 5786514]13.Hartman ML, Veldhuis JD, Thorner MO. Normal control of growth hormone secretion. Horm Res. 1993;40(1-3):37-47. [PubMed: 8300049]

Disclosure: Joshua Brinkman declares no relevant financial relationships with ineligible companies.

Disclosure: Muhammad Ali Tariq declares no relevant financial relationships with ineligible companies.

Disclosure: Logan Leavitt declares no relevant financial relationships with ineligible companies.

Disclosure: Sandeep Sharma declares no relevant financial relationships with ineligible companies.

Copyright © 2025, StatPearls Publishing LLC.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

Bookshelf ID: NBK482141PMID: 29489209 Share

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• Cite this PageBrinkman JE, Tariq MA, Leavitt L, et al. Physiology, Growth Hormone. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-.

In this Page

• Introduction
• Cellular Level
• Function
• Related Testing
• Clinical Significance
• Review Questions
• References

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