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

R. N. Trivedi, Subhash Chauhan, A. Dwivedi, V. P. Kamboj, M. M. Singh

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)367-379
Number of pages13
JournalContraception
Volume51
Issue number6
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

Fingerprint

Estrogen Receptor Modulators
Estrogen Receptors
Estradiol
Estrogens
Centchroman
Weights and Measures
Nafoxidine
Weight Gain
Tamoxifen
triphenylethylene
Horns
Cytoplasmic and Nuclear Receptors
Oral Contraceptives
Progesterone
Oral Administration
Therapeutics

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Time-related effects of a triphenylethylene antiestrogen on estrogen-induced changes in uterine weight, estrogen receptors, and endometrial sensitivity in rats. / Trivedi, R. N.; Chauhan, Subhash; Dwivedi, A.; Kamboj, V. P.; Singh, M. M.

In: Contraception, Vol. 51, No. 6, 01.01.1995, p. 367-379.

Research output: Contribution to journalArticle

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