Effect of endothelin-1 in man—impact on basal and stimulated concentrations of luteinizing hormone, follicle-stimulating hormone, thyrotropin, growth hormone, corticotropin, and prolactin with and without pretreatment with nifedipine

Abstract

In healthy men, intravenous (IV) endothelin-1 suppresses the growth hormone (GH)-releasing hormone (GHRH)-stimulated increase in GH and prolactin (PRL) and augments corticotropin (ACTH)-releasing factor (CRF)-stimulated secretion of ACTH. Since some actions of endothelin-1 on pituitary function in vitro are antagonized by calcium channel antagonists, we have studied the effect of pretreatment with oral nifedipine (10 mg, given before infusion of endothelin-1 or vehicle) on basal and stimulated concentrations of pituitary hormones in a group of healthy men (N = 6). The augmentative effect of endothelin-1 on CRF-induced ACTH secretion ( P < .05) was counteracted by pretreatment with nidefipine. Pretreatment with nifedipine further inhibited ( P < .01) the GHRH-induced increase in plasma concentrations of GH ( P < .05), which, in keeping with previous data, had already been reduced by IV endothelin-1 alone ( P < .05). Thus, both endothelin-1 and nifedipine influence pituitary hormone secretion in healthy man. However, nifedipine does not ubiquitously counteract the effects of endothelin-1 since it enhances some of its actions on the pituitary and diminishes others. Endothelin-1 may therefore influence pituitary function by mechanisms other than activation of calcium channels alone.