EFFECT OF NITRIC-OXIDE ON RAT ADRENAL ZONA-FASCICULATA STEROIDOGENESIS

The present study was designed to investigate the role of nitric oxide (NO) in the regulation of adrenocortical function. Different NO donor s, such as sodium nitroprusside (SNP), S-nitroso-L-acetyl penicillamin e, diethylamine/NO complex sodium salt and diethylenetriamine NO adduc t, significantly decreased corticosterone production both in unstimula ted and in corticotropin-stimulated zona fasciculata adrenal cells, in a dose-dependent manner. The effect of SNP was reversed by ferrous he moglobin. A selective inhibitor of NO synthase, L-N-G-nitro-arginine s ignificantly increased corticosterone secretion. The effect of SNP was not mediated by cGMP as permeable cGMP analogs did not reproduce its inhibitory effect. SNP significantly inhibited the steroidogenesis sti mulated by 8Br-cAMP and 22(R)OH-cholesterol, but was ineffective when corticosterone was produced in the presence of exogenously added pregn enolone. Moreover, the conversion of [H-3]cholesterol to [H-3]pregneno lone and the production of pregnenolone or progesterone (assessed by R IA) were significantly decreased by SNP. Taken together, these results suggest that NO may be a negative modulator of adrenal zona fascicula ta steroidogenesis.