Showing papers by "Benita S. Katzenellenbogen published in 1976"
TL;DR: Chemical modifications of the estriol molecule which result in a prolonged stimulation of uterine growth and metabolism also result in the long-term maintenance of hormone-receptor complex in the uterine nucleus.
Abstract: The temporal relationships between hormone receptor binding and early and late biological responses in the uterus were examined using estriol (E3), a weak estrogen, and several morelong acting estriol derivatives, namely ethinyl estriol (EE3) (estriol cyclopentyl ether (E3CPE), and ethinyl estriol)cyclopentyl ether (EE3CPE). Dose-response curves) of 3–day uterotrophic assays indicate that biological (potency follows the order EE3CPE > EE3 or estradiol > E3 CPE > E3 After a single injection of 5 ⁄μ.g of compound, E3 elicits the early uterotrophic responses (increased uterine wet weight and 2–deoxyglucose phosphorylation at 2–6 h) but gives only weak stimulation of later uterotrophic responses (enhanced rates of 2–deoxyglucose phosphorylation at 20–24 h and increased DNA synthesis rate and uterine weight (over a 72 h period). E3, EE3 and estradiol all elicit a rapid (maximal by ½–1 h) uptake of receptor into the nucleus and show an equivalent wet weight response at 3 h. After E3 nuclear receptor levels and ...
129 citations
TL;DR: The studies indicate that the in vitro and in vivo effects of androgens on the uterus are clearly different and suggest that the actions of androgen on the uterine in vivo are probably not directly mediated through the estrogen receptor system.
Abstract: High concentrations of androgens in itro [10-6 and 10-7M 5α-dihydrotestosterone (DHT) and testosterone (T)] translocate the estrogen receptor from the cytoplasmic to the nuclear fraction of the immature rat uterus, and the androgen translocated sites are capable of eliciting the synthesis of the specific uterine “induced protein” (IP), formerly attributed to estrogenic compounds only. The magnitude of receptor translocation and IP synthesis induction is related to the concentration of androgen, and, at equal concentrations, DHT is more effective than T. Competitive protein-binding assays with cell-free uterine cytosol indicate that DHT and T bind with barely detectable affinity to the cytosol estrogen receptor [relative binding ability ca. 0.001% that of estradiol (E2)], and radioactive E2 uptake into whole uterus after pretreatment with androgens indicates that the androgentranslocated nuclear sites are readily filled by E2. DHT and T translocate the estrogen receptor to the nucleus in vitro, and the sal...
53 citations