Modulation of glucocorticoid metabolism by the growth hormone - IGF-1 axis.
The growth hormone-insulin-like growth factor 1 (GH-IGF-1) axis plays an important role in modulating the peripheral metabolism of glucocorticoids mainly through its effect on the isoenzyme 11 beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) which, in vivo, functions as a reductase catalysing the conversion of cortisone to cortisol. Several in vivo and ex vivo studies have shown that the GH-IGF-I system inhibits the expression and activity of 11beta-HSD1 in adipose tissues and the liver resulting in reduced local regeneration of cortisol. This interaction has clinically significant implications as it may at least partly explain the phenotypes of acromegaly and adult GH deficiency and the effects that treatment of these conditions has on body composition. In addition, by accelerating the peripheral metabolism of cortisol, GH therapy may precipitate adrenal insufficiency in susceptible hypopituitary patients, and endocrinologists should be mindful of this phenomenon when starting hypopituitary patients on GH replacement therapy.
Agha
Amar
A
Department of Endocrinology, St. Bartholomew's Hospital; William Harvey Research Institute, Queen Mary University of London, UK. amaragha@beaumont.ie
Monson
John P
JP
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism; D050154:Adiposity; D000309:Adrenal Insufficiency / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000328:Adult; D003348:Cortisone / Q000378:metabolism; D013006:Growth Hormone / Q000172:deficiency / Q000502:physiology*; D019382:Human Growth Hormone / Q000627:therapeutic use; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007018:Hypopituitarism / Q000188:drug therapy; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000378:metabolism*
D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D003348:Cortisone; D006854:Hydrocortisone