Physiology of growth hormone
- Shlomo Melmed, MD
Shlomo Melmed, MD
- Senior Vice President and Dean
- Cedars Sinai Medical Center
- Professor of Medicine
- University of California at Los Angeles School of Medicine
Growth hormone (GH) is produced by the pituitary somatotroph cells. GH production begins early in fetal life and continues throughout life, although at a progressively lower rate.
The basic aspects of GH physiology will be reviewed here. This discussion will include the GH gene, the mechanisms and regulators of GH secretion, and a summary of the actions of GH. The physiology of insulin-like growth factor 1 (IGF-1), which mediates most peripheral actions of GH, is discussed separately. (See "Physiology of insulin-like growth factor 1".)
Clinical issues related to GH excess (acromegaly) or GH deficiency in children and adults are also presented separately. (See "Treatment of growth hormone deficiency in children" and "Pituitary gigantism" and "Growth hormone deficiency in adults" and "Causes and clinical manifestations of acromegaly".)
The human growth hormone (GH) gene family comprises five distinct genes, all located on chromosome 17q22 . The pituitary GH gene (GH-N) encodes two alternatively spliced mRNA products, which give rise to the abundant circulating 22 kDa GH molecule and a less abundant (10 percent of circulating GH) 20 kDa GH lacking amino acids 32 to 46. Placental syncytiotrophoblast cells express a GH variant (hGH-V) as well as three other genes for human chorionic somatotropin (hCS). During pregnancy, maternal GH secretion declines and is replaced by rising placental-derived GH. (See "Maternal endocrine and metabolic adaptation to pregnancy", section on 'Anterior pituitary'.)
Regulation of the pituitary GH-N gene appears to be under complex hormonal, developmental, and tissue-specific control mediated by regulatory elements of the gene . The tissue-specific development of somatotrophs and expression of GH appear to be largely determined by the POU1F1 (Pit-1) transcription factor . (See "Principles of molecular genetics".)
- Brooks AJ, Waters MJ. The growth hormone receptor: mechanism of activation and clinical implications. Nat Rev Endocrinol 2010; 6:515.
- Ho Y, Liebhaber SA, Cooke NE. Activation of the human GH gene cluster: roles for targeted chromatin modification. Trends Endocrinol Metab 2004; 15:40.
- Voss JW, Rosenfeld MG. Anterior pituitary development: short tales from dwarf mice. Cell 1992; 70:527.
- Procter AM, Phillips JA 3rd, Cooper DN. The molecular genetics of growth hormone deficiency. Hum Genet 1998; 103:255.
- Wu W, Cogan JD, Pfäffle RW, et al. Mutations in PROP1 cause familial combined pituitary hormone deficiency. Nat Genet 1998; 18:147.
- Pellegrini-Bouiller I, Bélicar P, Barlier A, et al. A new mutation of the gene encoding the transcription factor Pit-1 is responsible for combined pituitary hormone deficiency. J Clin Endocrinol Metab 1996; 81:2790.
- Mullis PE. Genetics of GHRH, GHRH-receptor, GH and GH-receptor: its impact on pharmacogenetics. Best Pract Res Clin Endocrinol Metab 2011; 25:25.
- Mullis PE. Genetics of growth hormone deficiency. Endocrinol Metab Clin North Am 2007; 36:17.
- Leung KC, Ho KK. Measurement of growth hormone, insulin-like growth factor I and their binding proteins: the clinical aspects. Clin Chim Acta 2001; 313:119.
- Hartman ML, Veldhuis JD, Thorner MO. Normal control of growth hormone secretion. Horm Res 1993; 40:37.
- Giustina A, Veldhuis JD. Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev 1998; 19:717.
- Frohman LA, Jansson JO. Growth hormone-releasing hormone. Endocr Rev 1986; 7:223.
- Chanson P, Cailleux-Bounacer A, Kuhn JM, et al. Comparative validation of the growth hormone-releasing hormone and arginine test for the diagnosis of adult growth hormone deficiency using a growth hormone assay conforming to recent international recommendations. J Clin Endocrinol Metab 2010; 95:3684.
- Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999; 402:656.
- Pong SS, Chaung LY, Dean DC, et al. Identification of a new G-protein-linked receptor for growth hormone secretagogues. Mol Endocrinol 1996; 10:57.
- Zhao TJ, Liang G, Li RL, et al. Ghrelin O-acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice. Proc Natl Acad Sci U S A 2010; 107:7467.
- Shimon I, Taylor JE, Dong JZ, et al. Somatostatin receptor subtype specificity in human fetal pituitary cultures. Differential role of SSTR2 and SSTR5 for growth hormone, thyroid-stimulating hormone, and prolactin regulation. J Clin Invest 1997; 99:789.
- Ben-Shlomo A, Melmed S. Pituitary somatostatin receptor signaling. Trends Endocrinol Metab 2010; 21:123.
- Jaffe CA, DeMott-Friberg R, Barkan AL. Endogenous growth hormone (GH)-releasing hormone is required for GH responses to pharmacological stimuli. J Clin Invest 1996; 97:934.
- Unger RH. The hyperleptinemia of obesity-regulator of caloric surpluses. Cell 2004; 117:145.
- Van Cauter E, Leproult R, Plat L. Age-related changes in slow wave sleep and REM sleep and relationship with growth hormone and cortisol levels in healthy men. JAMA 2000; 284:861.
- Toogood AA, Nass RM, Pezzoli SS, et al. Preservation of growth hormone pulsatility despite pituitary pathology, surgery, and irradiation. J Clin Endocrinol Metab 1997; 82:2215.
- Reutens AT, Veldhuis JD, Hoffman DM, et al. A highly sensitive growth hormone (GH) enzyme-linked immunosorbent assay uncovers increased contribution of a tonic mode of GH secretion in adults with organic GH deficiency. J Clin Endocrinol Metab 1996; 81:1591.
- Goldenberg N, Barkan A. Factors regulating growth hormone secretion in humans. Endocrinol Metab Clin North Am 2007; 36:37.
- Salvatori R. Growth hormone and IGF-1. Rev Endocr Metab Disord 2004; 5:15.
- Chapman IM, Hartman ML, Straume M, et al. Enhanced sensitivity growth hormone (GH) chemiluminescence assay reveals lower postglucose nadir GH concentrations in men than women. J Clin Endocrinol Metab 1994; 78:1312.
- Iranmanesh A, Grisso B, Veldhuis JD. Low basal and persistent pulsatile growth hormone secretion are revealed in normal and hyposomatotropic men studied with a new ultrasensitive chemiluminescence assay. J Clin Endocrinol Metab 1994; 78:526.
- Reutens AT, Hoffman DM, Leung KC, Ho KK. Evaluation and application of a highly sensitive assay for serum growth hormone (GH) in the study of adult GH deficiency. J Clin Endocrinol Metab 1995; 80:480.
- Woelfle J, Chia DJ, Rotwein P. Mechanisms of growth hormone (GH) action. Identification of conserved Stat5 binding sites that mediate GH-induced insulin-like growth factor-I gene activation. J Biol Chem 2003; 278:51261.
- Bidlingmaier M, Freda PU. Measurement of human growth hormone by immunoassays: current status, unsolved problems and clinical consequences. Growth Horm IGF Res 2010; 20:19.
- Barnard R, Waters MJ. The serum growth hormone binding protein: pregnant with possibilities. J Endocrinol 1997; 153:1.
- Eugster EA, Pescovitz OH. New revelations about the role of STATs in stature. N Engl J Med 2003; 349:1110.
- Frank SJ. Growth hormone signalling and its regulation: preventing too much of a good thing. Growth Horm IGF Res 2001; 11:201.
- Leung KC, Waters MJ, Markus I, et al. Insulin and insulin-like growth factor-I acutely inhibit surface translocation of growth hormone receptors in osteoblasts: a novel mechanism of growth hormone receptor regulation. Proc Natl Acad Sci U S A 1997; 94:11381.