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 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 up-regulated or down-regulated by E2.
Medlock
K L
KL
Department of Health and Human Services, Food and Drug Administration, National Center for Toxicological Research, Division of Reproductive and Developmental Toxicology, Jefferson, Arkansas 72079-9502.
Forrester
T M
TM
Sheehan
D M
DM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004343:Drug Implants; D004347:Drug Interactions; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005260:Female; D007279:Injections, Subcutaneous; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011374:Progesterone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism
D004343:Drug Implants; D011960:Receptors, Estrogen; D011374:Progesterone; D004958:Estradiol