Hyperprolactinemia is one of the most common disorders in endocrinology. A role for PRL on the human adrenal gland has been postulated in various clinical studies. We have demonstrated for the first time the expression of the PRL receptor in the human adrenal gland and in human adrenal primary cell cultures using PCR and immunohistochemical methods. Using immunostaining, we could detect the PRL receptor in all three zones of the adrenal cortex. Only weak staining was observed in the adrenal medulla. The influence of PRL on the secretion of cortisol, aldosterone, and androgens in human primary cell cultures was investigated. After stimulation with PRL (10(-7) mol/L), we measured increased concentrations of cortisol (155 +/- 9.8%; P < 0.005%), aldosterone (122 +/- 3.7%; P < 0.005), and dehydroepiandrosterone (121 +/- 8.6%; P < 0.05) in the cell supernatant. PRL did not affect the expression of messenger ribonucleic acid of cytochrome P45017 alpha in human adrenal cell cultures. In conclusion, we found the PRL receptor in the human adrenal gland. We postulate that PRL has a direct effect on adrenal steroidogenesis, thereby regulating adrenal function, which may be of particular relevance in clinical disorders with hyperprolactinemia.