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  • 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.


Structure of Human Growth Hormone

Human growth hormone (hGH, or somatotropin) is a globular protein with a molecular mass of 22 kDa. It consists of a single polypeptide chain of 191 amino acid residues, with two disulfide bridges and no carbohydrate moieties (Fig. 202-1).1-3 Growth hormones (GH) from cattle, sheep, and pigs are very similar, although not identical in structure, to hGH, but all are sufficiently different to render them inactive in humans.4 The hGH molecule is predominantly α-helical in its secondary structure. While most of the hGH contained in the pituitary gland is the 22-kDa form shown in Fig. 202-1, four other variants (one 45 kDa, two 24 kDa, and one 20 kDa) have been identified.4 The 45-kDa variant is an aggregate or ...

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