Atrial natriuretic hormone (ANH) is found in heart myocytes, and also in the CNS. The inhibitory action of ANH on the hypothalamic-pituitary-adrenocortical (HPA) system has been established by in vivo and in vitro experiments, and could be of considerable importance: whereas several synergists to corticotropin-releasing hormone (CRH), the key hormone of the HPA system, are characterized in the past, until now ANH seems to be the only peptide which counterbalances the effects of CRH at the pituitary. As well as at the corticotroph, CRH has a stimulatory influence upon the lactotroph in vivo, and like ACTH and corticosteroids prolactin (PRL) is released in response to physical and cognitive challenges. To test the hypothesis of whether ANH also inhibits the CRH-mediated prolactin release a randomized, placebo-controlled, double-blind study in 12 males aged from 25 to 30 years was conducted. With regard to the diurnal variation of the HPA system activity we compared the prolactin release by 100 micrograms hCRH during a 30 min infusion of placebo, 150 micrograms ANH or 3 IU arginine vasopressin in the morning (08:00 h) and evening (19:00 h). Evaluation of morning and evening effects revealed that administration of hCRH led to a prompt rise of plasma PRL concentration. Infusion of ANH resulted in a significantly reduced maximum increment of PRL compared to placebo (0.83 +/- 0.87 vs 2.85 +/- 1.57 ng/ml, mean +/- SD, n = 12, p < .001). In addition, the AUC values were significantly lower under ANH than in the placebo condition. Infusion of AVP did not significantly change the PRL response to CRH vs placebo.(ABSTRACT TRUNCATED AT 250 WORDS)