Nitric oxide stimulates growth hormone secretion in vitro through a calcium- and cyclic guanosine monophosphate-independent mechanism

In the last years, nitric oxide (NO) has emerged as an important intra- and intercellular transmitter involved in the control of the hypothalamic-pitu itary axis, and NO synthase (NOS) has been identified in pituitary cells. T o determine the role of NO in the control of GH secretion acting directly a t the pituitary level, we have studied GH release by hemipituitaries incuba ted in the presence of different concentrations (10(-7) -10(-3) M) Of sodiu m nitro-prusside (SNP), a potent NO donor. We found that SNP (10(-4)-10(-3) M) stimulated GH release. This effect was mediated by the release of NO si nce it was abolished in the presence of hemoglobin, a scavenger of NO, but preserved in the presence of rhodanese + sodium thiosulfate (inactivators o f cyanides generated from SNP]. To analyze the participation of cyclic guan osine monophosphate (cGMP), the second messenger for a wide range of NO act ions, in SNP-stimulated GH secretion, hemipituitaries were incubated in the presence of 8-bromo-cGMP (8-Br-cGMP; 10(-7)-10(-3) M). In addition, hemipi tuitaries were stimulated with SNP plus oxadiazoloquinoxaline (OQD) or LY 8 3,583 (inhibitors of guanylyl cyclases). We found that 8-Br-cGMP was ineffe ctive in eliciting GH release, and that the stimulatory effect of SNP was m aintained in presence of OOD and LY 83,583. Finally, to analyze calcium dep endence, the SNP effect was studied in hemipituitaries incubated in free me dium calcium, in the presence of nifedipine and verapamil (blockers of calc ium channels) and after depletion of intracellular Ca2+ stores with caffein e. We found that the SNP-induced GH secretion is also detected after incuba tion of hemipituitaries in free calcium medium, in the presence of nifedipi ne and verapamil, and after caffeine preincubation. We conclude that NO sti mulates GH secretion in vitro through a specific calcium-cGMP-independent m echanism. Copyright (C) 1999 S. Karger AG, Basel.