Anti-mitogenic action of opioid peptides on epidermal growth factor-stimulated uterine cells

Endogenous opioid peptides are negative regulators of estradiol-induced ute rine cell proliferation. To investigate the possible molecular target site( s) of their anti-mitogenic action, we examined the effect of opioid peptide s on epidermal growth factor-induced cell proliferation both in uterine pri mary cell cultures prepared from adult rats and in human myometrial smooth muscle cell lines. Epidermal growth factor (EGF) significantly increased ce ll density in both types of cultured monolayers. This EGF-induced stimulati on of cell proliferation was blocked by [D-Met(2)-Pro(5)]enkephalinamide in a time-dependent, receptor-mediated manner. The effective concentrations w ere within the physiological nanomolar range. Enkephalinamide did not have any effect on the basal rate of proliferation of the uterine cells. Our res ults on this novel physiological cross-talk suggest that shared step(s) of the mechanism of action of estradiol and EGF might be targeted by opioid pe ptides and not the general machinery of cell proliferation. (C) 2001 Elsevi er Science B.V. All rights reserved.