Time-related effects of a triphenylethylene antiestrogen on estrogen-induced changes in uterine weight, estrogen receptors, and endometrial sensitivity in rats

• Published in: Contraception (Stoneham) Vol. 51; no. 6; pp. 367 - 379
• Main Authors: Trivedi, R.N., Chauhan, S.C., Dwivedi, A., Kamboj, V.P., Singh, M.M.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-06-1995; Elsevier Science
• Subjects: Administration, Oral; Animals; Biological and medical sciences; Birth control; centchroman; Centchroman - administration & dosage; Centchroman - pharmacology; Decidua - drug effects; Decidua - physiology; Dose-Response Relationship, Drug; duration of antiestrogenic/antideciduogenic action; endometrial sensitivity; Endometrium - drug effects; Endometrium - metabolism; Endometrium - physiology; Epithelium - chemistry; Epithelium - drug effects; Epithelium - ultrastructure; Estradiol - pharmacology; Estrogen Antagonists - administration & dosage; Estrogen Antagonists - pharmacology; estrogen receptors; Female; Gynecology. Andrology. Obstetrics; histology; immature rats; Induced abortion. Therapeutic abortion; Medical sciences; Microscopy, Electron, Scanning; nafoxidine; Nafoxidine - pharmacology; Organ Size - drug effects; Organ Size - physiology; Ovariectomy; Progesterone - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Estrogen - analysis; Receptors, Estrogen - metabolism; tamoxifen; Tamoxifen - pharmacology; Time Factors; ultrastructure; uterine weight; Uterus - anatomy & histology; Uterus - drug effects; Uterus - physiology; duration of antiestrogenic/antideciduogenic action; uterine weight; histology; centchroman; immature rats; endometrial sensitivity; ultrastructure; nafoxidine; estrogen receptors; tamoxifen; Vertebrata; Mammalia; Rat; Uterus; Animal; Rodentia; Antiestrogen; Oral administration; Tamoxifene; Duration of action; Nafoxidine
• ISSN: 0010-7824; 1879-0518
• DOI: 10.1016/0010-7824(95)00103-H

Time-related estrogen antagonistic action of a single oral contraceptive (1.25 mg/kg) dose of the triphenylethylene antiestrogen centchroman was determined in ovariectomized immature rats. Tamoxifen and nafoxidine were used for comparison. A single oral administration of centchroman followed by three doses of estradiol-17β (1 μg/d, s.c.) caused significant dose-dependent inhibition in estradiol-17β-induced increase in uterine weight and nuclear and cytosolic estrogen receptors. But the inhibition at anti-implantation dose was evident only if estradiol-17β treatment was initiated not later than 48 h post-antiestrogen. Alternatively, when antiestrogen treatment was followed by a single dose of estradiol-17β between days 2–7, a synergistic action, typical of antiestrogens possessing weak estrogen agonistic activity, was observed. In immature rats in which a condition mimicking preimplantation was produced by estradiol-17β (0.5 μg/d, s.c.) priming on days -2 and -1, followed by progesterone (1 mg/d, s.c.) and an endometrial sensitizing dose (0.5 μg/d, s.c.) of estradiol-17β at 1600 h on day 4, anti-implantation dose of centchroman administered on day 1, too, failed to inhibit uterine weight gain induced by sensitizing dose of estradiol-17β, but caused marked inhibition in endometrial sensitivity to a deciduogenic stimulus and decidualization and weight gain of traumatized uterine horn 96 h post-traumatization over non-traumatized horn was only about 150% (725% in controls). Inhibition in endometrial sensitivity and decidualization was evident when the interval between antiestrogen treatment and sensitizing estradiol was <126 h. Pinopods were present on endometrial surface on day 5 whether or not priming and/or sensitizing doses of estradiol were administered, but decidual response was mild if either of these doses of estradiol-17β was deferred. Findings suggest that: (a) duration of antiestrogenic action of single anti-implantation dose of centchroman in rat was about 126 h, which in ovariectomized immature rats was evident only when a condition mimicking preimplantation was produced and the antiestrogenic response was based on inhibition in estradiol-induced endometrial sensitivity and not uterine weight gain; (b) priming as well as sensitizing estrogen were essential to get optimal decidual responses; (c) appearance of pinopods on endometrial surface may not be related to endometrial sensitivity; and (d) tamoxifen and nafoxidine appear slightly longer acting with duration of antiestrogenic action of ∼150 h.