The role of nitric oxide derived from l-arginine in the control of steroidogenesis, and perfusion medium flow rate in the isolated perfused rat adrenal gland

Abstract

The present studies were designed to investigate the role of nitric oxide (NO) in the regulation of adrenocortical function, using the intact rat adrenal gland in situ, perfused with medium (Hank's balanced salt solution) containing a range of concentrations of L-arginine, the substrate for NO production. In addition, the effects of NG-nitro-L-arginine methylester (L-NAME), an inhibitor of NO production, were investigated. Results showed that L-arginine caused a dose-dependent increase in the flow rate of the perfusion medium through the adrenal gland. This effect was specific, as neither D-arginine nor L-lysine had an effect. The presence of L-NAME (5 mmol/l) in perfusion medium containing L-arginine caused a decrease in flow rate to levels in the absence of L-arginine. In the presence of concentrations of L-arginine up to 500 mumol/l, corticosterone secretion rates were also stimulated in a dose-dependent manner. Further studies, investigating the effect of L-arginine on the response to ACTH(1-24) stimulation, found that the percentage increase in flow rate, aldosterone secretion and corticosterone secretion caused by ACTH were not significantly different using media containing 230 mumol L-arginine/l or in the absence of L-arginine. These results suggest a role for NO derived from L-arginine in the regulation of basal levels of adrenal vascular tone in the rat isolated adrenal gland preparation. They do not suggest an obligatory role for NO in either the vascular or steroidogenic response to ACTH stimulation.

The rapid release of corticosterone from the adrenal induced by ACTH is mediated by nitric oxide acting by prostaglandin E 2

“…Our present results indicate that NO stimulates corticosterone release from adrenals in vitro. These results are in concordance with those of previous authors (16), demonstrating that L-arginine, the substrate of NO, caused a dose-dependent increase in corticosterone secretion. We believe that NO leads to a rapid release of stored corticosterone from the adrenals, because release at 15 min was nearly as great as at 30 min.…”

“…NO is generated by L-arginine oxidation in a complex enzymatic reaction catalyzed by a NO synthase (NOS) family found in many tissues, including the AG (14,15). In addition, increasing evidence suggests NO involvement in steroid biosynthesis regulation (13,16). Because endothelial and neuronal cells have a close anatomical proximity to steroidogenic cells in the AG, and these cells release NO, one study suggested that endothelial or neural NOS could be effective in regulating steroid release (13).…”

“…Epinephrine, one of the main products of the adrenal medulla, probably stimulates StAR expression through cAMP production (24). There are controversial reports on the effects of NO and PGs on the steroidogenic pathway (13,16,17). All of these studies used dispersed cells, thereby eliminating the normal architecture of the gland.…”

Effect of nitric oxide on rat adrenal zona fasciculata steroidogenesis

“…However, it has been shown that the administration of -NAME induces the activation of the hypothalamicpituitary-adrenal axis through an increase of ACTH plasma levels (Giordano et al 1996). Since these experiments were performed in vivo, systemic effects induced by the inhibition of the basal NO tone, such as an increase in blood pressure (Cameron & Hinson 1993) cannot be ruled out.…”

“…Adams et al (1991) reported that in vivo treatment with -NAME resulted in a dosedependent increase in testosterone and corticosterone secretion without any effect at the anterior pituitary level, but an increase in plasma adrenocorticotropin (ACTH) concentrations induced by the administration of -NAME in vivo was also described (Giordano et al 1996). On the contrary, it has been reported that corticosterone secretion in isolated perfused adrenals is inhibited by -NAME (Cameron & Hinson 1993). Concurrently, Nakayama et al (1996) found that -NMMA prevented the ACTHstimulated production of aldosterone in isolated rat adrenal glands.…”