PROGESTERONE AND ESTRADIOL INTERACTION IN THE REGULATION OF RAT UTERINE WEIGHT AND ESTROGEN-RECEPTOR CONCENTRATION

Autologous down-regulation of hormone receptors has been shown for sev eral steroid hormones. We have previously shown estradiol (E(2)) regul ates estrogen receptor (ER) in ovarlectomized (OVX) rats. These studie s have been extended to investigate the interaction between progestero ne (P) and E(2) in the regulation of ER and uterine weight. We implant ed Silastic capsules containing varying concentrations of E(2) (0.0005 mg E(2)/ml to 5.0 mg E(2)/ml of sesame oil) Into adult female Sprague -Dawley rats one week after OVX. Simultaneously with implantation, P i njections were started (sc in sesame oil) at doses of 1-40 mg/day for three days. In the absence of P, the 0.05 mg E(2)/ml implant significa ntly increased total ER levels (measured by cytosol and nuclear exchan ge assays) by 25%, while the two highest concentrations of E(2) (0.5 a nd 5.0 mg E(2)/ml) significantly decreased cytosol and total ER levels by at least 40%. No P dose altered ER levels in OVX rats or in rats g iven E(2) implants of 0.01 mg E(2)/ml or lower. At E(2) implant concen trations of 0.05 mg E(2)/ml and higher, P decreased total ER levels 30 %-50% compared to the appropriate E(2)-only controls. P increased uter ine weight by 25% in OVX controls end in rats treated with E(2) implan ts of 0.01 mg E(2)/ml and below. In contrast, P inhibited uterine weig ht gain induced by 0.05-5.0 mg/E(2) ml implants by 20%-30%; maximal in hibition occurred at 5 mg/day of P and above. These data demonstrate t hat P increases uterine weight but does not alter ER concentration in rats with low E(2) levels (OVX or low E(2) concentration implants) but decreases uterine weight and down-regulates ER at higher E(2) levels, regardless of whether ER is upregulated or down-regulated by E(2).