Effect of dopamine, dopamine D-1 and D-2 receptor modulation on ACTH and cortisol levels in normal men and women

Abstract

Abstract. The regulation of the hypothalamic-pituitary-adrenal axis by dopamine is not fully understood. Therefore, we have studied the effect of dopamine, metoclopramide, a D-2 receptor antagonist, and fenoldopam, a specific D-1 receptor agonist, on ACTH and cortisol levels in normal subjects. Normal women received 5-h infusions of either glucose (N = 6) or dopamine at rates of 0.04 (N = 6), 0.4 (N = 6) and 4.0 μg · kg−1· min−1 (N = 8). After 3 h, 10 mg metoclopramide was given iv. No intergroup differences regarding ACTH and cortisol levels were observed (p>0.05). In a second study six women received dopamine (4.0 μg·kg−1·min−1) or glucose for 18 h. During the infusions cortisol and ACTH levels were similar on the two study days. Administration of metoclopramide (10 mg) after 17 h induced a significant increase in cortisol levels during dopamine infusion (p<0.05), whereas no effect was observed during placebo infusion. ACTH levels were unaffected by metoclopramide. In a third study, 9 normal women and 9 normal men received fenoldopam (0.5 μg·kg −1·min−) or placebo infusions for 3 h. In males, median ACTH and cortisol levels were significantly lower (p<0.05) during fenoldopam compared with placebo infusion. In contrast, fenoldopam did not affect ACTH and cortisol levels in normal women. The results suggest that the effect of dopamine D-1 receptor stimulation on ACTH and cortisol secretion is mainly at the hypothalamic level and that this effect is sex-dependent. In addition, we hypothesize that raised dopaminergic activity for a prolonged period of time may have an inhibitory effect on the hypothalamic-pituitary-adrenal axis. This may be triggered by low estrogen levels.