Serotonin and adrenocorticotropin (ACTH) release: direct effects at the anterior pituitary level and potentiation of arginine vasopressin-induced ACTH release.

Abstract

Many reports indicate that serotonin (5-HT) has a role in the regulation of the secretion of ACTH and related peptides. The present study was designed to evaluate in vitro a possible direct effect of 5-HT upon ACTH release from the anterior pituitary and also to determine if any interactions between the amine and different peptides with corticotropin-releasing activity (CRA) take place at the pituitary level. Dispersed anterior pituitary cells from donor adult male rats were incubated in the presence of 5-HT, quipazine (a 5-HT agonist), and metergoline (METER; a 5-HT receptor blocker) at different concentrations and also with synthetic arginine vasopressin (AVP) and corticotropin-releasing factor at several concentrations, alone or combined with some of the drugs mentioned above. In addition, several concentrations of acidic median eminence (ME) extracts were run alone or in combination with METER. The results indicate that 5-HT consistently elicited a small, but significant, release of ACTH in a dose-dependent fashion. This effect of 5-HT was completely blocked by the addition of METER to the cell incubates at concentrations of 10-6 and 10-8 M, whereas partial suppression was achieved with a METER concentration of 10 -10 M. Similarly, quipazine stimulated ACTH release, but at concentrations larger than those required for 5-HT. 5-HT potentiated the release of ACTH induced by AVP at concentrations of 1 and 10 ng AVP/ml incubated cells). This potentiation was also completely suppressed in the presence of 10-6 M METER. In contrast, the CRA of corticotropin-releasing factor (at doses of 0.2, 1, and 10 ng/ml), which by itself was severalfold more active than AVP, was not modified by the addition of 5-HT and/or METER. Finally, the CRA of rat ME extracts at two different doses was significantly depressed in the presence of METER. These results indicate: 1) that 5-HT can affect ACTH release by acting directly at the anterior pituitary level, an observation in line with recent reports (26) describing an uptake system for 5-HT in the rat pituitary; 2) that 5-HT potentiates the activity of AVP, suggesting an intriguing amine-peptide interaction at the pituitary level; and 3) that the latter interaction may be a component of the overall CRA of ME extracts, since blockade of 5-HT receptors consistently blunted the in vitro ACTH release elicited by ME extracts.