Molecular Human Reproduction, Vol. 5, No. 6, 565-572,
June 1999
© 1999 European Society of Human Reproduction and Embryology
Opioid peptides inhibit the action of oestradiol on human myometrial cells in culture*
1 Institute of Physiology, and 2 Department of Obstetrics & Gynecology, University Medical School of Pécs, Pécs, Szigeti str. 12, H-7643 Hungary, and 3 Department of Obstetrics & Gynecology, University of Louisville, Louisville, KY 40292, USA
The effect of opioid peptides on cultured, oestradiol-stimulated human myometrial cells was examined. Oestradiol increased cell densities in mixed-cell (smooth muscle cells + stromal fibroblasts) cultures by 40%. This oestradiol-induced stimulation of cell proliferation was decreased to control values by D-met2-pro5-enkephalinamide. The half-effective inhibitory concentration 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. This opioid effect was mediated dominantly by the mu opiate receptor. The optimal concentration for oestradiol to stimulate uterine cell proliferation was 2.2 nM. The basal rate of cell proliferation was not affected by enkephalinamide. In saturation experiments, the parameters of specific [3H]-naloxone binding were: dissociation constant = 1.02 nM, maximal binding capacity = 2910 binding sites/cell, Hill coefficient = 1.029. In human myometrial pure smooth muscle cell cultures, oestradiol decreased the proliferation of cells. Progesterone potentiated these oestradiol effects, but had no effect on its own. Enkephalinamide was also able to block the effects of oestradiol, but naloxone did not antagonize it. In summary, here we present a novel inhibitory role of endogenous opioid peptides in the regulation of cell growth and proliferation in the human uterus.
human/oestradiol/opiates/proliferation/uterus
*This study was presented in part at the 4th European Congress of Endocrinology of the European Federation of Endocrine Societies, Seville, Spain, 1998.
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