PLASMA GROWTH-HORMONE (GH) RESPONSES TO CORTICOTROPIN-RELEASING HORMONE IN PATIENTS WITH ACROMEGALY - THE EFFECT OF DEXAMETHASONE PRETREATMENT AND THE COMPARISON WITH GH RESPONSES TO THYROTROPIN-RELEASING-HORMONE, GONADOTROPIN-RELEASING-HORMONE AND GH-RELEASING HORMONE

It has been reported that paradoxical GH responses to corticotropin-releasing hormone (CRH) occur in only few patients with acromegaly. However, we have observed such responses in 7 of 14 active acromegalic patients. Therefore, we have studied the GH responses to thyrotropin-releasing hormone (TRH) (500-mu-g, iv), gonadotropin-releasing hormone (LHRH) (100 -mu-g, iv) and GH-releasing hormone (GHRH) (100-mu-g, iv) in these patients to examine the relationships between the GH responses to CRH and the responses to these hypothalamic hormones. Further, these patients received human CRH (1-41) NH2 (100-mu-g, iv) With or without dexamethasone (Dex) pretreatment (1 mg/100 ml saline, iv, from -30 to + 30 min) to study the mechanism of CRH-induced GH secretion, and a perifusion experiment was performed using adenoma tissue obtained at surgery from one patient (10(-7)M CRH and TRH were added) to elucidate whether CRH acts directly at the pituitary level. Aberrant GH responses induced by CRH were found in 7 of 14 (50%) acromegalic patients (TRH responders: 10/13, 77%; LHRH responders: 2/9, 22%; GHRH responders: 10/12,83%). In these patients, percent GH increment induced by CRH ranged from 81 to 144% (Mean +/- SE, 118 +/- 8%), and the GH peak (19 +/- 3 min) appeared as early as after TRH (23 +/- 4 min, N = 10). Plasma GH responses to CRH were not affected by Dex pretreatment in 4 acromegalic patients (AUC of GH responses: before, 3730 +/- 1339; after Dex, 3867 +/- 1616-mu-g/L min), whereas plasma ACTH responses of 7 patients including CRH nonresponders were significantly suppressed (AUC of ACTH responses: before, 181 +/- 1827; after Dex, 1090 +/- 384-mu-g/L-min) (p = 0.0156). In the perifusion experiment, CRH also stimulated GH release as well as TRH. These results indicate that: i) Paradoxical GH responses to CRH in acromegalic patients are not so rare, suggesting multiple abnormalities of the cell membrane of the tumor somatotrophs; ii) The relationship between CRH and glucocorticoids as is present in normal corticotrophs is lacking in GH adenoma cells.