Dual and Selective Actions of Glucocorticoids upon Basal and Stimulated Growth Hormone Release in Man

Abstract

In humans, corticoids suppress growth and growth hormone (GH) secretion elicited by a variety of stimuli, while in the rat they potentiate both in vivo and in vitro GH release. To further study this problem, growth-hormone-releasing hormone (GHRH) tests were performed in 6 nonobese Cushing''s syndrome patients and 6 controls. The normal GHRH-induced GH secretion was completely abolished in the Cushing''s syndrome group. To study the action of shorter corticoid exposures, 34 volunteers were subjected to four tests each: placebo treatment (control); dexamethasone (Dex) administration 4 mg i.v., 3 h before; Dex 8 mg p.o., 12 h before, and Dex 22 mg p.o. over the 2 days before the pituitary challenge that was always administered at 0 min (12.00 h). In the first test (n = 9), GHRH (1 .mu.g/skg i.v.) induced a GH peak of 14.5 .+-. 3.8 ng/ml (control) that was potentiated by Dex 4 mg i.v. administered 3 h before (26.4 .+-. 6.8 ng/ml). On the contrary, longer Dex treatments suppress GHRH-induced GH values (6.0 .+-. 1.1 ng/ml after Dex 8 mg and 1.8 .+-. 0.3 ng/ml after Dex 22 mg). Clonidine administration 300 .mu.g p.o. (n = 7) increased GH secretion with an area under the secretory curve (AUC) of 1,274 .+-. 236 that was potentiated by Dex 4 mg i.v. given 3 h before clonidine (2,380 .+-. 489) and reduced by Dex 8 mg, the reduction being significant only after 22 mg Dex (595 .+-. 47). When arginine 30 g was used as pituitary challenge (n = 6), the GH peak (19.1 .+-. 4.8 ng/ml) and the AUC (1,318 .+-. 322) were not significantly altered by Dex 4 mg nor by Dex 8 mg, but clearly reduced after pretreatment with Dex 22 mg (11.1 .+-. 4.6 ng/ml peak; 635 .+-. 189 AUC).The action of Dex was rather selective for GH secretion, because it did not alter (n = 6) prolactin, luteinizing hormone and follicle-stimulating hormone stimulated by a combined administration of leuteinizing-hormone-releasing hormone and thyrotropin-releasing hormone. In this group, thyrotropin was only altered after the higher (22 mg) Dex treatment. These results showed a dual action of Dex on GH release in man. Short-term treatment potentiated basal and GHRH-stimulated GH secretion. The stimulatory action of corticoids becomes in inhibitory one when longer treatments are employed, suggesting, though not proving, to be mediated by somatostatin release from the hypothalamus.