TY - CHAP M1 - Book, Section TI - Inherited Defects in Growth Hormone Synthesis and Action A1 - Cogan, Joy D. A1 - Phillips, John A. A2 - Valle, David L. A2 - Antonarakis, Stylianos A2 - Ballabio, Andrea A2 - Beaudet, Arthur L. A2 - Mitchell, Grant A. PY - 2019 T2 - The Online Metabolic and Molecular Bases of Inherited Disease AB - Human growth hormone (hGH, or somatotropin) is essential for normal postnatal growth. It is a 191-amino acid protein that is released from the anterior pituitary gland on stimulation by growth hormone-releasing hormone (GHRH, or somatocrinin), a factor produced by the hypothalamic region of the brain. Like other pituitary hormones, hGH acts on target tissues, in this case primarily the liver, to cause synthesis and release of a second hormone mediator, insulin-like growth factor (IGF) I, also called somatomedin C, into the systemic circulation. IGF-I is a growth-accelerating peptide that acts directly on cartilage to promote bone growth.Deficiency of human growth hormone (hGH) production causes metabolic alterations and growth failure. While most cases of hGH deficiency are idiopathic, 17 known single gene disorders as well as a variety of other genetic disorders and syndromes are associated with deficiency of hGH or defective action. These genetic disorders are caused by alterations in the hGH gene, alterations of distant loci (such as Pit-1, Prop-1, or GHRHR) that cause hGH deficiency through epistatic effects, or alterations of genes (such as the growth hormone receptor gene (GHR)) that affect the response to hGH.Deficiency of hGH was treated in the past by replacement with exogenous hGH isolated from cadaver pituitaries. Because of the accompanying danger of transmission of infectious neurodegenerative disease (Creutzfeldt-Jakob disease; MIM 123400), alternative methods of treatment are now used. These include replacement with biosynthetic hGH or, in some cases, treatment with GHRH. The potential for hGH gene therapy has been demonstrated in animals.Human chorionic somatomammotropin (hCS, or human placental lactogen) has similar biologic activities, but it is much less potent than hGH. During pregnancy, maternal hCS levels are very high and approximately 300 times greater than fetal levels. While human chorionic somatomammotropin (hCS) is thought to be important in maternal carbohydrate and fat metabolism, normal fetal growth occurs in pregnancies in which it is absent.Two genetic disorders of the hCS loci have been described. While these alterations lead to deficiency or absent hCS production, affected individuals are thought to be asymptomatic. SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/03/28 UR - ommbid.mhmedical.com/content.aspx?aid=1181453850 ER -