MODULATION OF PROLACTIN SECRETION IN HUMAN MYOMETRIUM BY CYTOKINES

Prolactin (PRL) secretion and PRL mRNA expression in human myometrial explant cultures was inhibited by the addition of human placental conditioned medium (HPCM). After 3 days treatment with 5% HPCM PRL secretion was reduced to 24% of control values (P < 0.001). The effect persisted even after removal of progesterone, which suppresses myometrial PRL production, from the HPCM. In search for additional regulatory substances present in the uteroplacental unit, we tested a number of growth factors and cytokines known to affect pituitary PRL secretion. Treatment with endothelin-3 (ET-3) at a dose of 10(-6) M was found to increase PRL release by 20% over 3 days (P < 0.05) whereas interleukin-6 (IL-6) showed no effect on PRL levels. Epidermal growth factor, vasoactive intestinal peptide and interferon-alpha (IFN-ar) were inhibitory. Interleukin-4(IL-4) was the most potent inhibitor of PRL expression in myometrial tissue, causing a reduction of secreted PRL to less than 50% of controls after 3 days at a dose of greater than or equal to 5 ng/ml (P < 0.001) and a concomitant reduction of PRL mRNA levels. These results demonstrate a modulation of PRL expression in the myometrium by locally present factors.