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

  • Albert J. Peters
    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
    Geisinger Medical Center, Division of Obstetrics and Gynecology, Section of Reproductive Endocrinology, Danville, PA 17822, USA
    Search for articles by this author
  • Anne Colston Wentz
    Northwestern University Medical School, Department of Obstetrics and Gynecology, Section of Reproductive Endocrinology, Prentice Women's Hospital, Chicago, IL 60611, USA
    Search for articles by this author
  • Ralph R. Kazer
    Northwestern University Medical School, Department of Obstetrics and Gynecology, Section of Reproductive Endocrinology, Prentice Women's Hospital, Chicago, IL 60611, USA
    Search for articles by this author
  • Rajasingam S. Jeyendran
    Northwestern University Medical School, Department of Obstetrics and Gynecology, Section of Reproductive Endocrinology, Prentice Women's Hospital, Chicago, IL 60611, USA
    Search for articles by this author
  • Robert T. Chatterton Jr.
    Northwestern University Medical School, Department of Obstetrics and Gynecology, Section of Reproductive Endocrinology, Prentice Women's Hospital, Chicago, IL 60611, USA
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.


      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.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Contraception
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Jordan VC
        Biochemical pharmacology of antiestrogen action.
        Pharm Rev. 1984; 36: 245-276
        • Nishino Y
        • Schneider MR
        • Michna H
        • Von Angerer E
        Pharmacological characterization of a novel oestrogen antagonists ZK 119010, in rats and mice.
        J Endocrinol. 1991; 130: 409-414
        • Peters AJ
        • Khanna A
        • Wentz AC
        • Chatterton Jr, RT
        Hormone receptor-binding properties of the primary metabolite of the contraceptive anordrin.
        in: 74th Annual Meeting of the Endocrine Society [Abstracts]. 1992: 236
        • Chatterton Jr., RT
        • Berman C
        • Walters NN
        Antiuterotrophic and folliculostatic activities of anordiol (2α,17α-diethynyl-A-nor-5α-androstane-2β,17β-diol.
        Contraception. 1989; 39: 291-297
        • Mehta RR
        • Jenco JM
        • Chatterton Jr., RT
        Antiestrogenic and antifertility actions of anordrin.
        Steroids. 1981; 38: 679-691
        • Gu Z-P
        • Chang MC
        A-nor steroids as post-coital contraceptives in the hamster with special reference to the transport and degeneration of eggs.
        Contraception. 1979; 20: 549-557
        • Lu Y-C
        • Chatterton Jr, RT
        Effect of anordiol on ovarian hormone secretion, ovulation, and uterine and vaginal responses in the immature rat.
        Adv Contraception. 1994; 10: 157-166
        • Chatterton Jr., RT
        • Walters NN
        • Waller DP
        Preclinical studies of anordrin: ovulation inhibition, pharmacokinetics, metabolism, and toxicity.
        in: Mizuno M Proceedings of the Satellite Symposium on Hormonal Contraception, International Congress of Endocrinology. Keidanren Kaikan, Tokyo1988: 25-32
        • Mehta RR
        • Jenco JM
        • Chatterton Jr., RT
        • Venton D
        Antagonism of the actions of estrogens, androgens, and progesterone by anordrin.
        Steroids. 1982; 40: 65-80
        • Adashi EY
        Clomiphene citrate: mechanism(s) and site(s) of action—A hypothesis revisited.
        Fertil Steril. 1984; 42: 331-344
        • Adashi EY
        • Hsueh AJ
        • Bambino TH
        Disparate effects of clomiphene and tamoxifen on pituitary gonadotropin release in vitro.
        Am J Physiol. 1981; 240: E125-E130
        • Miyake A
        • Tasaka K
        • Sakumoto T
        • Kawamura Y
        • Nagahara Y
        • Aono T
        Clomiphene citrate induces luteinizing hormone release through hypothalamic-releasing hormone in vitro.
        Acta Endocrinol. 1983; 103: 289-292
        • Engels JA
        • Friedlander RL
        • Eik-Nes KB
        Effect in vivo of clomiphene on the rate of conversion of androstenedione-C14 to estrone-C14 and estradiol-C14 by the canine ovary.
        Metabolism. 1968; 17: 189-198
        • Adashi EY
        • Hsueh AJ
        Estrogens augment the stimulation of ovarian aromatase activity by follicle stimulating hormones in cultured rat granulosa cells.
        J Biol Chem. 1982; 257: 6077-6083
        • Cummings AM
        • Perreault SD
        • Harris ST
        Validation of protocols for assessing early pregnancy failure in the rat: clomiphene citrate.
        Fund Appl Toxicol. 1991; 16: 506-516
        • DeFeo VJ
        Temporal aspects of uterine sensitivity in the pseudopregnant or pregnant rat.
        Endocrinology. 1963; 72: 306-316
        • Kurowski TT
        • Chatterton Jr., RT
        • Hickson RC
        Glucocorticoid-induced cardiac hypertrophy: additive effects of exercise.
        J Appl Physiol. 1984; 57: 514-519
        • Giudice LC
        • Dsupin BA
        • Jin IH
        • Vu TH
        • Hoffman AR
        Differential expression of messenger ribonucleic acids encoding insulin-like growth factors and their receptors in human uterine endometrium and decidua.
        J Clin Endocrinol Metab. 1993; 76: 1115-1122
        • Scatchard G
        The attraction of proteins for small molecules and ions.
        Ann N Y Acad Sci. 1949; 51: 666-672
        • Hinegardner RT
        An improved fluorometric assay for DNA.
        Anal Biochem. 1971; 39: 197-201
        • Ku C-P
        • Chu M-K
        • Chiang H-C
        • Chao S-H
        • Pang T-W
        • Tsou K
        Pharmacological studies of a contraceptive drug anordrin.
        Chinese Med J. 1976; 2: 177-184
        • Hu C-Y
        • Wang W-C
        • Hwang T-M
        • et al.
        Endometrial and hormonal changes induced by anordrin.
        in: Diczfaluzy E Fraser IS Webb FTG Endometrial Bleeding and Steroidal Contraception. Proceedings of a Symposium on Steroid Contraception and Mechanisms of Endometrial Bleeding. Pitman Press Ltd, Bath, England1980: 191-200
        • Chang CC
        • Wang WC
        • Bardin CW
        Postcoital use of anordrin and RU 486 for prevention of implantation in the rat.
        Contraception. 1993; 47: 413-419
        • Lu Y-C
        • Chatterton Jr, RT
        Effects of the antiestrogen anordiol on ovulation and endometrial histology in the rat.
        Adv Contraception. 1993; 9: 257-268
        • Caligaris L
        • Astrada JJ
        • Taleisnik S
        Release of luteinizing hormone induced by estrogen injection into ovariectomized rats.
        Endocrinology. 1971; 88: 810-815
        • Chatterjee A
        • Pal AK
        • Gupta T
        Pregnant mare's serum gonadotropin: II. Reversal of the antifertility faculty of pregnant mare's serum gonadotropin using clomiphene citrate or reserpine in rats.
        Contraception. 1977; 15: 571-578
        • Barkai U
        • Kidron T
        • Kraicer PF
        Inhibition of decidual induction in rats by clomiphene and tamoxifen.
        Biol Reprod. 1992; 46: 733-739
        • Schlough JS
        • Meyer RK
        Suppression of the decidual response with estrogen antagonists.
        Fertil Steril. 1965; 16: 596
        • Chou YC
        • Iguchi T
        • Bern HA
        Effects of antiestrogens on adult and neonatal mouse reproductive organs.
        Reprod Toxicol. 1992; 6: 439-446
        • Chetrite G
        • Pasqualini JR
        Biological responses of ICI 164,384 and other anti-estrogens in vaginal and uterine cells of fetal guinea pig in culture.
        Acta Endocrinol (Copenh). 1991; 125: 401-408
        • Yee GM
        • Kennedy TG
        Prostaglandin E2, cAMP and cAMP-dependent protein kinase isozymes during decidualization of rat endometrial stromal cells in vitro.
        Prostaglandins. 1993; 46: 117-138
        • Bell SC
        Comparative aspects of decidualization in rodents and human: cell types, secreted products and associated function.
        in: Edwards RG Purdy JM Steptoe PC Implantation of the Human Embryo. Academic Press, London1985: 71-122
        • Mani SK
        • Julian J
        • Lampelo S
        • Glasser SR
        Initiation and maintenance of in vitro decidualization are independent of hormonal sensitization in vivo.
        Biol Reprod. 1992; 47: 785-799
        • Sreenivasulu S
        • Singh MM
        • Dwivedi A
        • Setty BS
        • Kamboj VP
        CDRI-85/287, a novel antiestrogen and antiimplantation agent: biological profile and interaction with the estrogen receptors in immature rat uterus.
        Contraception. 1992; 45: 81-92
        • Clark JH
        • Schrader WT
        • O'Malley BW
        Mechanism of action of steroid hormones.
        in: Wilson JD Foster DW Williams Textbook of Endocrinology. 8th ed. W.B. Saunders, Philadelphia1992: 35-90