Prolactin has a direct effect on adrenal androgen secretion.

The role of PRL in the secretion of androgens by the adrenal glands was investigated in vivo and in vitro. In women with hyperprolactinemia whose pituitary-adrenal function was normal, there was significant correlation between serum PRL and dehydroepiandrosterone sulfate [(DHEA-S) gamma = 0.48, P less than 0.05, n = 34] and DHEA (gamma = 0.50, P less than 0.05, n = 34), but not with androstenedione. Long term administration of sulpiride to normal women increased both serum PRL and DHEA-S, whereas acute elevation of PRL after a single iv dose of domperidone had no influence on the serum DHEA-S levels. Monolayer cultures of human adrenal cells were used in order to study the direct effect of PRL on adrenal androgen secretion. The daily secretion of DHEA-S, DHEA, androstenedione, and cortisol was determined. In the absence of ACTH, PRL had no effect on steroid secretion in a 7-day culture period. In the presence of ACTH, there was a daily increase in the secretion of steroids. PRL, when added in combination with ACTH, potentiated the effect of ACTH on DHEA-S and DHEA but not on androstenedione and cortisol secretion on the seventh day in culture. These results indicate that PRL has a direct synergistic effect with ACTH on adrenal cells to increase adrenal androgen release. Increases in DHEA-S and DHEA but not androstenedione in vitro and correlation between serum PRL and DHEA-S and DHEA but not androstenedione in women with hyperprolactinemia suggest that the synergistic effect of PRL on adrenal androgen secretion may result from partial inhibition of adrenal 3 beta-hydroxysteroid dehydrogenase.