Advertisement
Research Article| Volume 9, ISSUE 4, P393-401, April 1974

A relationship between estrogenicity and antifertility activity of 1-diphenylmethylenyl-2-methyl-3-ethyl-4-acetoxycyclohexane (ORF 8511) and similar nonsteroidal anti-implantive agents

      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      Several nonsteroidal estrogens, such as ORF 3858 and F6103, which inhibit pregnancy in experimental animals when given postcoitally, have been previously described. ORF 8511 (1-diphenylmethylenyl-2-methyl-3-ethyl-4-acetoxycyclohexane) which is structurally similar to these compounds was studied for its postcoital antifertility activity and estrogenicity in rats, hamsters, mice and rabbits. Results of these studies suggest a relationship between these two biological endpoints. ORF 8511 produced uterotropic stimulation in the rat at microgram doses and totally inhibited implantation at 250 μg/kg/day administered on days 1–6 of pregnancy. However, the other species were considerably less sensitive to the compound with respect to both parameters. The compound stimulated tubal transport in rats at its minimum effective dose for antifertility activity as did diethylstilbestrol, a known estrogen. In the hamster, a species relatively insensitive to the antifertility effect of ORF 8511, endogenous estrogen titres during early pregnancy were higher than those in the rat. These data suggest that ORF 8511 and similar nonsteroidal compounds may owe their postcoital antifertility activity to their estrogenicity and that estrogens may act as pharmacological agents only in species with low normal endogenous estrogen titres.
      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:

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

      References

        • Blye R.P.
        The Effect of Estrogens and Related Substances on Embryonic Viability.
        in: Raspe G. Advances in the Biosciences. Pergamon Press, New York1970
        • Einer-Jensen N.
        Antifertility Properties of two diphenylethene.
        Acta Pharmacol. (Kbh.). 1968; 1: 1-97
        • Emmens C.W.
        Postcoital Contraception.
        Brit. Med. Bull. 1970; 26: 45
        • Lerner L.J.
        The Biology of Nonsteroidal Antifertility Agents.
        in: Lednicer D. Contraception. Marcel Dekker, Inc, New York1969
        • Bacic M.
        • Engstrom L.
        • Johannisson E.
        • Leideman T.
        • Diczfalusy E.
        Effect of F6103 on Implantation and Early Gestation in Women.
        Acta Endocrinol. 1970; 64: 705-717
        • Hahn D.W.
        • Allen G.O.
        • McGuire J.L.
        • DaVanzo J.P.
        Species Differences in the Estrogenicity and Postcoital Antifertility Activity of ORF 8511 (1-Diphenylmethylenyl-2-methyl-3-ethyl-4-acetoxy-cyclohexane).
        in: Fed. Proc.32. 1973: 268
        • McGuire J.L.
        • Brookes P.H.
        • Culver R.M.
        • Hahn D.W.
        The Relationship of Endogenous Estrogen Levels to the Efficacy of Estrogenic Postcoital Antifertility Agents.
        The Pharmacologist. 1973; 15: 256
        • Greenwald G.S.
        Species Differences in Egg Transport in Response to Exogenous Estrogen.
        Anat. Rec. 1967; 157: 163-172
        • Hotchkiss J.
        • Atkinson L.E.
        • Knobil E.
        Time Course of Serum Estrogen and Luteinizing Hormone (LH) Concentrations During the Menstrual Cycle of the Rhesus Monkey.
        Endocrinol. 1971; 89: 177-183
        • Speroff L.
        • Caldwell B.V.
        • Brock W.A.
        • Andersen G.G.
        • Hobbins J.C.
        Hormone Levels During Prostaglandin F2α Infusions for Therapeutic Abortion.
        J. Clin. Endocr. Metab. 1972; 34: 531-536
        • Blye R.P.
        • Homm R.
        Antizygotic Activity of 2-methyl-3-ethyl-4-phenyl-4-cyclohexene carboxylic acid.
        in: Fed. Proc.26. 1967: 486
        • Yard A.S.
        • Juhasz L.P.
        • Grimes R.M.
        Studies on the Antifertility Effect and Metabolism of a New Postcoital Oral Contraceptive, 2-methyl-3-ethyl-4-phenyl-Δ4-cyclohexene carboxylic acid, sodium salt (ORF 4563).
        J. Pharmacol. Exp. Thera. 1969; 167: 105
        • McGuire J.L.
        • Turner G.D.
        • Greenslade F.C.
        The Effect of 2-methyl-3-ethyl-4-phenyl-Δ4-cyclohexene-carboxylic Acid (ORF 3858) and its ϱ-hydroxylated Metabolites on Uptake of 3H-estradiol-17β by the uterus.
        in: Proc. Soc. Exp. Biol. Med.136. 1971: 146-149
        • Shaikh A.A.
        Estrone and Estradiol Levels in the Ovarian Venous Blood from Rats During the Estrous Cycle and Pregnancy.
        Biol. Reprod. 1971; 5: 297-307
        • Shaikh A.A.
        Estrone, Estradiol, Progesterone and 17α-hydroxyprogesterone in the Ovarian Venous Plasma During the Estrous Cycle of the Hamster.
        Endocrinol. 1972; 91: 1136-1140
        • Hori T.
        • Ide M.
        • Miyake T.
        Ovarian Estrogen Secretion During the Estrous Cycle and Under the Influences of Exogenous Gonadotropins in Rats.
        Endocrinol. Japon. 1968; 5: 215
        • Crooke A.C.
        • Butt W.R.
        • Carrington S.P.
        • Morris R.
        • Planer R.F.
        • Edwards R.L.
        Pregnancy in Women with Secondary Amenorrhea Treated with Human Gonadotropin.
        Lancet. 1964; 1: 184