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The role of cortisol in influencing spontaneous and 5HT mediated prolactin release was investigated in 17 healthy male subjects who took part in 3 separate studies. Five of the subjects were treated for 24 h with metyrapone (the 11 beta-hydroxylase inhibitor which prevents the conversion of 11-deoxycortisol to cortisol) on one occasion and placebo for 24 h on another. On both test occasions their spontaneous prolactin was monitored before they underwent serotonergic-stimulated prolactin release using D-fenfluramine (30 mg). Treatment with metyrapone enhanced the spontaneous nocturnal prolactin surge and also the prolactin response to D-fenfluramine. Six of the subjects were treated for 24 h with hydrocortisone on one occasion or placebo on the other. With hydrocortisone treatment no nocturnal increase in prolactin was observed and the response to D-fenfluramine challenge was attenuated. To determine whether the influence of cortisol on prolactin release is at a pituitary or supra-pituitary site 6 subjects were tested with thyrotropin releasing hormone (TRH) which acts directly on the pituitary to bring about prolactin release. They were each tested twice, following either metyrapone or placebo treatment. The rise following metyrapone was significantly greater than that seen following placebo. The results suggest that cortisol influences both spontaneous and 5HT stimulated PRL release, probably acting at a pituitary level.

The Influence of Cortisol on Spontaneous and 5HT Stimulated Prolactin Release in Man