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 μ, iv), gonadotropin-releasing hormone (LHRH) (100 μg, iv) and GH-releasing hormone (GHRH) (100 μg, 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 μg, 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 (10-7M 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 responded: 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 μg/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 μg/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 corticotropins is lacking in GH adenoma cells.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism