Opioid peptides inhibit the action of oestradiol on human myometrial cellsin culture

The effect of opioid peptides on cultured, oestradiol-stimulated human myom etrial cells was examined. Oestradiol increased cell densities in mixed-cel l (smooth muscle cells + stromal fibroblasts) cultures by 40%. This oestrad iol-induced stimulation of cell proliferation was decreased to control valu es by D-met(2)-pro(5)-enkephalinamide. The half-effective inhibitory concen tration of enkephalinamide was 0.3 nmol/l. The opioid-induced inhibition of cell proliferation was blocked completely by the specific opiate receptor antagonist naloxone, while naloxone did not have any effect on its own. Thi s opioid effect was mediated dominantly by the mu opiate receptor, The opti mal concentration for oestradiol to stimulate uterine cell proliferation wa s 2.2 nM. The basal rate of cell proliferation was not affected by enkephal inamide. In saturation experiments, the parameters of specific [H-3]-naloxo ne binding were: dissociation constant = 1.02 nM, maximal binding capacity = 2910 binding sites/cell, Hill coefficient = 1.029. In human myometrial pu re smooth muscle cell cultures, oestradiol decreased the proliferation of c ells. Progesterone potentiated these oestradiol effects, but had no effect on its own. Enkephalinamide was also able to block the effects of oestradio l, but naloxone did not antagonize it. In summary, here we present a novel inhibitory role of endogenous opioid peptides in the regulation of cell gro wth and proliferation in the human uterus.