Progesterone and Estradiol Interaction in the Regulation of Rat Uterine Weight and Estrogen Receptor Concentration

Abstract

Abstract

Autologous down-regulation of hormone receptors has been shown for several steroid hormones. We have previously shown estradiol (E₂) regulates estrogen receptor (ER) in ovariectomized (OVX) rats. These studies have been extended to investigate the interaction between progesterone (P) and E₂ in the regulation of ER and uterine weight. We implanted Silastic capsules containing varying concentrations of E₂ (0.0005 mg E₂/ml to 5.0 mg E₂/ml of sesame oil) into adult female Sprague-Dawley rats one week after OVX. Simultaneously with implantation, P injections 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 E₂/ml implant significantly increased total ER levels (measured by cytosol and nuclear exchange assays) by 25%, while the two highest concentrations of E₂ (0.5 and 5.0 mg E₂/ml) significantly decreased cytosol and total ER levels by at least 40%. No P dose altered ER levels in OVX rats or in rats given E₂ implants of 0.01 mg E₂/ml or lower. At E₂ implant concentrations of 0.05 mg E₂/ml and higher, P decreased total ER levels 30%-50% compared to the appropriate E₂-only controls. P increased uterine weight by 25% in OVX controls and in rats treated with E₂ implants of 0.01 mg E₂/ml and below. In contrast, P inhibited uterine weight gain induced by 0.05-5.0 mg/E₂ ml implants by 20%-30%; maximal inhibition occurred at 5 mg/day of P and above. These data demonstrate that P increases uterine weight but does not alter ER concentration in rats with low E₂ levels (OVX or low E₂ concentration implants) but decreases uterine weight and down-regulates ER at higher E₂ levels, regardless of whether ER is upregulated or down-regulated by E₂. [P.S.E.B.M. 1994, Vol 205]