Skip to main content
SpringerLink
Log in

Estrogenic and antiestrogenic properties of clomiphene citrate in laboratory mice

  • Published:
Journal of Biosciences Aims and scope Submit manuscript

Abstract

The estrogen agonistic and antagonistic properties of clomiphene citrate were investigated in the mice. Clomiphene citrate was tested at various doses of 0.1, 1.0, 10 and 100 μg for three consecutive days in immature and mature bilaterally ovariectomized mice. Clomiphene citrate showed uterotrophic activity in both immature and ovariectomized conditions. The lower doses of 0.1 and 1.0 μg were ineffective to show any uterotrophic stimulation. Clomiphene citrate at 10 μg dose produced 305.56% increase in uterine weight i.e., 27.70 ± 0.24 vs 6.83 ± 0.06 in immature and 182.27% i.e., 42.68 ± 1.12 vs 15.12 ± 0.57 in ovariectomized mice. Clomiphene citrate at 100 μg dose showed significant uterotrophic effect e.g., 435.57% i.e., 36.58 ±0.34 vs 6.83 ± 0.06 in immature and 586% i.e., 103.80 ± 0.60 in ovariectomized mice. When clomiphene citrate was administered in combination with 0.32 μg of estradiol 17-β it caused significant antagonistic effect (decrease in uterine weight) at 10 and 100 μg respectively. Clomiphene citrate at 10 μg dose produced 32% i.e., 28.93 ± 0.43 vs 38.04 ± 2.68 in immature and 35% i.e., 59.64±1.44 vs 83.34 ±0.25 in ovariectomized mice respectively. Histological observation clearly showed that clomiphene citrate at 10 and 100 μg doses did not cause any differential hypertrophy of the epithelial layer. Similar doses in combination with estradiol produced significant antagonistic effect on uterine weight and luminal epithelial cell height.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

CC:

Clomiphene citrate

OVX:

ovariectomized

FSH:

follicle stimulating hormone

LH:

luteinizing hormone

LHRH:

luteinizing hormone releasing hormone

E:

estradiol

References

  • Barnes L E and Meyer R K 1962 Effects of ethamoxytriphetol, MRL-37 and clomiphene on reproduction in rats;Fertil. Steril. 13 472–480

    Article  CAS  Google Scholar 

  • Boyar R M 1970 Effects of clomiphene citrate on pituitary FSH, FSH-RH, and release of LH in immature and mature rats;Endocrinology 86 629–633

    Article  CAS  Google Scholar 

  • Clark J H and Markaverich B M 1982 Agonistic and antagonistic properties of clomiphene: A review;Pharmacol, Ther. 15 467–519

    Article  Google Scholar 

  • Clark J H and Peck E J 1979Female sex steroids: Receptors and function (Berlin, Heidelberg, New York: Springer Verlag) pp 126–130

    Book  Google Scholar 

  • Clark J H and Guthrie S C 1981 Agonistic and antagonistic effects of clomiphene citrate and its isomers;Biol. Reprod. 25 667–672

    Article  CAS  Google Scholar 

  • Charles D 1962 M.R.L. 41 in the treatment of secondary amenorrhea and endometrial hyperplasia;Lancet 2 278–280

    Article  CAS  Google Scholar 

  • Charles D, Barr W, Bell E T, Brown J B, Forthery K and Loraine J A 1963 Clomiphene in the treatment of oligomenorrhea and amenorrhea;Am. J. Obstet. Gynecol. 86 913–922

    Article  CAS  Google Scholar 

  • Coppola J A and Perrine J W 1965 Influence of two nonsteroidal antiestrogens on vaginal opening and PMS induced ovulation in rats;J. Reprod. Fertil. 13 373–374

    Article  Google Scholar 

  • Docke F 1960 Ovulation-inducing action of clomiphene citrate in the rat;J. Reprod. Fertil. 24 45–54

    Article  Google Scholar 

  • Emmens C W 1965 Oestrogenic, antiestrogenic and anti-fertility activity;Acta Med. Philipp. 1 220–224

    CAS  PubMed  Google Scholar 

  • Emmens C W and Carr W L 1973 Further studies of compounds exhibiting prolonged antiestrogenic and anti-fertility activity in the mouse;J. Reprod. Fertil. 35 29–40

    Article  Google Scholar 

  • Greenblatt R B, Barfield W E, Jungck E C and Ray A W 1961 Induction of ovulation with MRL/41. Preliminary report;J. Am. Med. Assoc. 178 101–104

    Article  CAS  Google Scholar 

  • Greenblatt R B, Roy S, Mahesh V B, Barfield W E and Jungck EC 1962 Induction of ovulation;Am. J. Obstet. Gynecol. 84 900–912

    Article  Google Scholar 

  • Holtkamp D E, Greslin J G, Root C A and Lerner L J 1960 Gonadotropin inhibiting and anti-fecundity effect of chloramiphene;Proc. Soc. Exp. Biol. Med. 105 197–201

    Article  CAS  Google Scholar 

  • Hsueh A J W, Erickson G F and Yen S S C 1978 Sensitization of pituitary cells to luteinizing hormone releasing hormone by clomiphene citratein vitro;Nature (London) 273 57–59

    Article  CAS  Google Scholar 

  • Jordan V C, Dix C J and Prestwich G 1979 Inhibition of cell division and stimulation of progesterone receptor synthesis in rat estrogen target tissues by non-steroidal antiestrogens; inSteroid hormone receptor systems (eds) W W Leavitt and J H Clark (New York: Plenum Press) pp 133–156

    Chapter  Google Scholar 

  • Kaiser I H 1963 Pregnancy following clomiphene-induced ovulation in chiari-formmel syndrome;Am. J. Obstet. Gynecol. 87 149–151

    Article  CAS  Google Scholar 

  • Kang Y H, Anderson W A and Desombre E R 1975 Modulation of uterine morphology and growth by estradiol-17Β and an estrogen antagonist;J. Cell Biol. 64 682–691

    Article  CAS  Google Scholar 

  • Karkun J N and Mehrotra P K 1973 Studies on physiology and biochemistry of female genital tract: Response of uterus, cervix and vagina of albino rats tocis andtrans clomiphene in the presence or absence of estrogen;Indian J. Exp. Biol. 11 7–14

    CAS  PubMed  Google Scholar 

  • Koch Y, Dikstein S, Superstine E and Sulman F G 1971 The effect of promethazine and clomiphene on gonadotropin secretion in the rat;J. Endocrinol. 49 13–17

    Article  CAS  Google Scholar 

  • Martin L, Finn C A and Trinder G 1973 Hypertrophy and hyperplasia in the mouse uterus after estrogen treatment: An autoradiographic study;J.Endocrinol. 56 133–144

    Article  CAS  Google Scholar 

  • Martin L 1980 Estrogens, antiestrogens and the regulation of cell proliferation in the female reproductive tract invivo; inEstrogens in the environment (ed.) J Mclachlan (Amsterdam: Elsevier North Holland) pp 103–130

    Google Scholar 

  • Nagel S, Baier H and Taubert H D 1970 Contrasting actions ofcis and trans-clomiphene on the release of FSH and FSH-RH in the female rat;Horm. Metab. Res. 2 344–348

    Article  CAS  Google Scholar 

  • Pollard I and Martin L 1968 The oestrogenic and antiestrogenic activity of some synthetic steroids;Steroids 11 897–907

    Article  CAS  Google Scholar 

  • Riley G M and Evans T N 1964 Effects of clomiphene on an ovulatory ovarian function; Am.J. Obstet. Gynecol. 89 97–110

    Article  CAS  Google Scholar 

  • Rebar R, Judd H L, Yen S S C, Rakoff J, Vanderberg G and Naftolin F 1976 Characterization of the inappropriate secretion in polycystic ovary syndrome;J. Clin. Invest. 57 1320–1329

    Article  CAS  Google Scholar 

  • Ross G T, Cargille C M, Lipsett M B, Rayford P L, Marshall J R, Strott C A and Rodbard D 1970 Pituitary and gonadal hormones in women during spontaneous and induced ovulatory cycles;Recent Prog. Res. 26 1–62

    CAS  Google Scholar 

  • Roy S, Greenblatt R B, Mahesh V B and Jungck E C 1963 Further observation on its use in induction of ovulation in the human and on its mode of action;Fertil. Steril. 14 575–595

    Article  CAS  Google Scholar 

  • Roy S and Greenblatt R B 1964 Effects of clomiphene on the physiology of reproduction in the rat. II. Its oestrogenic and antiestrogenic actions;Acta Endocrinol. (Copenhagen) 47 657–668

    Article  CAS  Google Scholar 

  • Schally A V, Carter W H, Parlow A F, Saito M, Arimura A, Bowers C Y and Holtkamp OE 1970 Alteration of and FSH release in rat treated with clomiphene and its isomers;Am. J. Obstet. Gynecol. 107 1156–1167

    Article  CAS  Google Scholar 

  • Schulz K D, August S, Gasde K and Kramer G 1972 Studies on the anti-oestrogenic and oestrogen-like action of clomiphene citrate. Animal experiments;Gynecol. Invest. 3 135–141

    Article  CAS  Google Scholar 

  • Terenius L 1971 Structure-activity relationships of antiestrogens with regard to interaction with 17 Β-oestradiol in the mouse and vagina.Endocrinology 66 431–447

    CAS  Google Scholar 

  • Terenius L and Ljungkvist I 1972 Aspects on the mode of action of anti-estrogens and anti-progestogens;Gynecol. Invest. 3 96–107

    Article  CAS  Google Scholar 

  • Whitelaw M J 1963 Clomiphene citrate: Newer aspects of its use in prevention and treatment of infertility;Fertil. Steril. 14 540–546

    Article  CAS  Google Scholar 

  • Yen S S C, Vela P and Ryan K J 1970 Effect of clomiphene citrate in polycystic ovary syndrome: Relationships between serum and corpus luteum function;J. Clin. Endocrinol. 31 7–13

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Embryo Physiology Laboratory, Department of Zoology, Banaras Hindu University, 221 005, Varanasi, India

    Arun Kumar & Pranab L. Pakrasi

Authors
  1. Arun Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pranab L. Pakrasi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kumar, A., Pakrasi, P.L. Estrogenic and antiestrogenic properties of clomiphene citrate in laboratory mice. J. Biosci. 20, 665–673 (1995). https://doi.org/10.1007/BF02703306

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02703306

Keywords

Search

Navigation