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Estrogenic and antiestrogenic activities of anordiol: A comparison of uterine and vaginal responses with those of clomiphene citrate

  • Albert J. Peters
    Correspondence
    Narne and address for correspondence: Dr. Albert J. Peters, Geisinger Medical Center, Division of Obstetrics/Gynecology, Section of Reproductive Endocrinology, Danville, PA 17822, USA. Tel: 717/271-5620; Fax: 717/271-5629
    Affiliations
    Geisinger Medical Center, Division of Obstetrics and Gynecology, Section of Reproductive Endocrinology, Danville, PA 17822, USA
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  • Anne Colston Wentz
    Affiliations
    Northwestern University Medical School, Department of Obstetrics and Gynecology, Section of Reproductive Endocrinology, Prentice Women's Hospital, Chicago, IL 60611, USA
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  • Ralph R. Kazer
    Affiliations
    Northwestern University Medical School, Department of Obstetrics and Gynecology, Section of Reproductive Endocrinology, Prentice Women's Hospital, Chicago, IL 60611, USA
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  • Rajasingam S. Jeyendran
    Affiliations
    Northwestern University Medical School, Department of Obstetrics and Gynecology, Section of Reproductive Endocrinology, Prentice Women's Hospital, Chicago, IL 60611, USA
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  • Robert T. Chatterton Jr.
    Affiliations
    Northwestern University Medical School, Department of Obstetrics and Gynecology, Section of Reproductive Endocrinology, Prentice Women's Hospital, Chicago, IL 60611, USA
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      Abstract

      Anordiol (2α,17α-diethynyl-A-nor-5α-androstane-2β,17β-diol) has been variously characterized as an estrogen and as an antiestrogen. To more completely understand the pharmacological properties of this contraceptive steroid, simultaneous responses were studied in uterine, vaginal, and hepatic tissues. Rats received 4 daily sc injections with either anordiol, clomiphene citrate (CC), or the vehicle alone (C+) starting on the first day of pseudopregnancy. Uteri were traumatized on day 4 of pseudopregnancy, and rats were sacrificed 5 days later. A pseudopregnant group without uterine trauma served as a negative control (C-). Mean uterine weights per animal and cytosolic estrogen (EcR) and progesterone (PcR) receptor activities per g of DNA were all 5- to 7-fold greater in the C_ group than in the other groups (all p<0.05). However, anordiol and CC suppressed uterine weight without suppressing the stromal proliferative response; the DNA content of the uteri of anordiol- and CC-treated rats was similar to that of C+ rats. Vaginal tissue exhibited estrogenic responses to anordiol and CC with an increase in epithelial stratification compared to the C+ and C− groups even though no difference in levels of Math Eq of DNA were expressed 5 days after the last antiestrogen dose. Binding affinities and serum E2 and progesterone (P) concentrations were not statistically different among the groups. In conclusion, anordiol produced responses in the uterus and vagina of the pseudopregnant rat which were indistinguishable from those of CC, and, therefore, we conclude that anordiol acts on these tissues as an antiestrogen.
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