UTERINE OXYTOCIN GENE-EXPRESSION .2. INDUCTION BY EXOGENOUS STEROID-ADMINISTRATION

As we have recently shown, the gene encoding the hypothalamic nonapeptide oxytocin (OT) is expressed in the rat endometrial epithelium during late pregnancy and the estrous phase of the estrous cycle. To investigate the role of ovarian steroids in the regulation of uterine OT gene expression, Silastic capsules containing estradiol or progesterone were implanted into immature ovariectomized rats. Exposure to estradiol alone for 2 days caused a significant rise in OT mRNA. Administration of progesterone alone was without effect. However, a strong synergism was observed when the two hormones were applied together; progesterone potentiated the effect of estradiol by a factor of 7. In animals treated with steroids for 4 days, the removal of either the estradiol or progesterone capsule after day 2 led to a decrease in the total amount of OT mRNA accumulation, implying that the continued action of both steroids was required to achieve maximal OT mRNA levels. Immunocytochemical analysis demonstrated that the main site of steroid-induced uterine OT gene expression is the endometrial epithelium, the same site where endogenously induced OT gene expression occurs at the end of pregnancy. The OT mRNA levels achieved after 4 days of treatment with both steroids were comparable to those achieved at estrus or during pseudopregnancy, but corresponded to less than 20% of the levels present in the uterus on day 21 of pregnancy. These data suggest that in the uterus, the synergistic action of ovarian steroids represents an important, but probably not exclusive, regulator of OT gene expression.