It has been demonstrated that the regulatory pathways mediating basal and/or stimulus-induced prolactin (PRL) release in mammals are highly sensitive to adrenal corticoid inhibitory influence. We have investigated the effect of four different doses of dexamethasone (DEX) and the effect of adrenocorticotropin on PRL secretion in 197 patients (169 female, 28 male; age: 18-66 yr) with suspected hypercortisolemia--but only those with a normal glucocorticoid suppression test were involved in the study--and in 66 female patients (age: 18-39 yr) with suspected adrenocorticotropin-dependent hyperandrogenism. Overnight (1 mg), low-dose (0.5 mg every 6 h for 2 d), high-dose (2 mg every 6 h for 2 d), and long-lasting administration of DEX (0.5 mg every 6 h for 5 d) resulted in a significant decrease in PRL levels compared to the baseline. Similarly, a reduction in PRL levels could be detected following injection of adrenocorticotropin (250 microg). In hyperprolactinemic patients, the DEX-induced increase in PRL (APRL, expressed in percentage of baseline) was significantly larger compared with normoprolactinemic subjects in all groups except those who received high-dose DEX) or adrenocorticotropin. These data clearly indicate that the secretory function of PRL cells in humans is sensitive to changes in the activity of the hypothalamo-pituitary-adrenal axis in a dose-dependent manner.