Effects of estradiol and estradiol sulfamate on the uterus of ovariectomized or ovariectomized and hypophysectomized rats

Estradiol sulfamate (J995), estradiol-17 beta with a substituted sulfamate group in position 3, has much higher systemic estrogenic activity after ora l administration than 17 beta -estradiol (E2) due to reduced hepatic metabo lism of the drug. The lower dose necessary for achievement of adequate syst emic estrogenic effects results in a substantial reduction of otherwise com monly observed hepatic side-effects. This makes J995 a strong candidate as an estrogen suitable for oral administration. The present study was per-for med to examine and compare the effects of J995 and E2 on the uterus after o ral or subcutaneous administration to ovariectomized or ovariectomized + hy pophysectomized female rats, in particular on the levels of the estrogen re ceptor (ER) (alpha + beta), ER alpha mRNA and insulin-like growth factor-1 (IGF-I) mRNA. The ER levels were determined using a ligand binding assay an d the mRNA levels using solution hybridization. The doses of J995 or E2 wer e chosen to achieve comparable uterotrophic activity. The rats were treated with hormones for 7 days and the treatment was initiated 14 days after sur gery. We conclude that there are no major differences in the uterine respon se to treatment with J995 or E2 with respect to the effects on ER and ER al pha. mRNA levels. The IGF-I mRNA level though, is more affected by J995 tha n by E2 after 7 days of treatment, indicating a prolonged effect of J995. ( C) 2000 Elsevier Science Ltd. All rights reserved.