title: Acute dexamethasone suppression of ACTH secretion stimulated by human corticotrophin releasing hormone, AVP and hypoglycaemia.
abstract: In order to obtain more insight into the mechanisms regulating endogenous ACTH secretion in humans we studied the inhibitory effect of acute i.v. dexamethasone administration on ACTH release under various conditions. Six male volunteers were subjected to six different protocols. After combined i.v. injection of 100 micrograms corticotrophin releasing hormone (CRH) and 100 micrograms growth hormone releasing hormone (GRH) there was the expected rise in ACTH (area under the curve, 1053 +/- 204 (SE) (pmol/l) min) and cortisol (59788 +/- 10098 (nmol/l) min) rise which was suppressed by prior i.v. injection of 2 mg dexamethasone (ACTH: 444 +/- 63 (pmol/l) min; cortisol: 28528 +/- 2152 (nmol/l) min). Insulin hypoglycaemia (IH) led to a more pronounced ACTH and cortisol rise compared with CRH (6307 +/- 817 (pmol/l) min and 82080 +/- 21934 (nmol/l) min, respectively) which was not completely suppressed by prior pretreatment with dexamethasone (ACTH, 580 +/- 103 (pmol/l) min; cortisol: 55649 +/- 5821 (nmol/l) min). Combined AVP/CRH injection (10 IU/100 micrograms) after pretreatment with dexamethasone (344 +/- 41 (pmol/l) min for ACTH; 32832 +/- 3173 (nmol/l) min for cortisol) could not reproduce the ACTH secretion following IH after pretreatment with dexamethasone (579 +/- 103 (pmol/l) min for ACTH and 55649 +/- 5821 (nmol/l) min for cortisol). In all subjects a saline control with 2 mg dexamethasone was performed. These findings confirm the acute inhibitory effect of glucocorticoids on CRH-stimulated ACTH secretion. Since CRH-induced ACTH secretion is almost completely abolished by administration of dexamethasone the ACTH rise following IH after dexamethasone can not be mediated by endogenous CRH alone. Moreover, since the addition of AVP to CRH (after dexamethasone suppression) could not reproduce the ACTH rise during IH after dexamethasone pretreatment, an additional, yet unknown factor stimulating ACTH secretion may be involved. In the same protocols, no significant difference could be observed comparing IH and GRH induced GH secretion (4948 +/- 1172 (mU/l) min vs 3596 +/- 820 (mU/l) min, NS); furthermore, in contrast to results obtained by chronic steroid administration, acute i.v. dexamethasone pretreatment did not affect IH or GRH-induced GH secretion (4110 +/- 666 (mU/l) min vs 2916 +/- 462 (mU/l) min, NS). The GRH-stimulated GH secretion (3596 +/- 820 (mU/l) min) was not suppressed by prior intravenous treatment with dexamethasone (2916 +/- 504 (mU/l) min, NS).
authors.affiliation: Medizinishce Klinik Innenstadt, University of Munich, FR Germany.
authors.forename: J
authors.initials: J
authors.lastname: Hohnloser
authors.forename: K
authors.initials: K
authors.lastname: Von Werder
authors.forename: O A
authors.initials: OA
authors.lastname: Müller
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D006063:Chorionic Gonadotropin / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004347:Drug Interactions / Q000502:physiology; D005246:Feedback; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D007275:Injections, Intravenous; D007328:Insulin; D008297:Male; D010906:Pituitary Hormone-Releasing Hormones / Q000008:administration & dosage / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000502:physiology; D011388:Prolactin / Q000097:blood
chemical_list: D006063:Chorionic Gonadotropin; D007328:Insulin; D010906:Pituitary Hormone-Releasing Hormones; D001127:Arginine Vasopressin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone