Interaction between steroid hormones and endometrial opioids.

The opioids beta-endorphin and the dynorphins belong to two separate families of endogenous opioid peptides (EOP). They are produced not only in the central nervous system but also in nonneural tissues where, as it appears, they act locally via paracrine mechanisms. These opioids have been shown to be produced at multiple sites along the mammalian reproductive tract including the intrauterine cavity. The aim of the present work was to find out if the well differentiated human endometrial cell line of Ishikawa, which has been shown to be a good in vitro model for the study of the effects of steroid hormones on human epithelial endometrium, expresses these two EOP. Northern blot hybridization of RNA from these cells showed the presence of a 1.2-kb POMC and a 2.4-kb PDYN transcript. Radioimmunoassay and gel filtration chromatography characterization of the immunoreactive (IR) opioid peptides present in the culture media showed the presence of IR-beta-endorphin and IR-dynorphins. The apparent molecular weight of IR-beta-endorphin was that of authentic beta-endorphin while the bulk of the IR-dynorphin had an apparent molecular weight of 8 kd. The secretion of both opioids could be increased by KCl-induced depolarization. Estrogen and glucocorticoids decreased, in a dose- and time-dependent manner, the secretion of beta-endorphin from the Ishikawa cells while progesterone and dihydrotestosterone did not have a statistically significant effect. The antiprogestin-antiglucocorticoid RU486 acted as an agonist, i.e., it diminished beta-endorphin secretion possibly via glucocorticoid receptors. On the other hand, the secretion of dynorphins was not affected by any of the steroids tested while LHRH, the inducer of gonadotropins and anterior pituitary dynorphins secretion, provoked a time- and dose-dependent increase of their secretion without affecting that of beta-endorphin. These data suggest that the regulation of endometrial opioids production is type-specific. Thus, it is possible that each type of endometrial opioid participates in different local homeostatic loops and exerts distinct paracrine effects.