EFFECTS OF RETINOIC ACID AND ESTROGENS ON OXYTOCIN GENE-EXPRESSION INTHE RAT UTERUS - IN-VITRO AND IN-VIVO STUDIES

We and others have previously identified functional estrogen (E) and r etinoic acid (RA) response elements in the human and rat oxytocin (OT) gene promoters. Whereas there is no direct evidence for a significant role of E or RA in the regulation of rat hypothalamic OT gene express ion, we have recently demonstrated that in vivo adminstration of E str ongly stimulates uterine OT gene expression. Here, we show that in viv o administration of RA similarly induces a significant increase in ute rine OT gene expression. Moreover, we report that the E and RA effects are reproducible in vitro. Using short-term uterine organ explant cul tures derived from 18-day pregnant rats, we found that E (50 nM) and R A (0.4 nM) increased OT mRNA levels 5.2and S-fold, respectively, sugge sting a direct action of these agents on uterine OT gene expression. F inally, we analyzed uterine E and RA receptor gene expression during p regnancy. Using semi-quantitative Northern blot analysis, we found tha t mRNAs encoding the E receptor, the RA receptor alpha and RA receptor beta are present in rat uterus and that their levels rise by 3.7-, 3. 6- and 5.8-fold, respectively, between day 14 of gestation and term. T aken together, the data suggest that, at term, the rat uterus has an i ncreased capacity to respond to E and RA, and that both agents may be involved in mediating the dramatic increase of OT mRNA accumulation ob served in the uterus at term.