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. 1978 Apr;62(4):487–493. doi: 10.1111/j.1476-5381.1978.tb07752.x

Differential depletion of cytoplasmic high affinity oestrogen receptors after the in vivo administration of the antioestrogens, clomiphene, MER-25 and tamoxifen.

R N Kurl, I D Morris
PMCID: PMC1668047  PMID: 656695

Abstract

1 The in vivo actions of the oestrogen antagonists, MER-25 and tamoxifen upon the cytosol oestrogen receptors prepared from amygdala, hypothalamus, pituitary and uterus of rats were studied 24 h after drug administration. 2 There was a dose-related depletion of cytosol oestrogen receptors. However, the uterine and pituitary receptors were consistently affected at a lower dose than were those from the brain. 3 The ratios of the combined central ED50 to the combined peripheral ED50 were clomiphene 169 greater than MER-25 19.2 greater than tamoxifen 2.13. 4 The receptor changes were not related to biological activity monitored by serum luteinizing hormone levels and uterotrophic response. 5 The possible role of these drug effects in the induction of ovulation and future developments are discussed.

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Selected References

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  1. Chazal G., Faudon M., Gogan F., Rotsztejn W. Effects of two estradiol antagonists upon the estradiol uptake in the rat brain and peripheral tissues. Brain Res. 1975 May 23;89(2):245–254. doi: 10.1016/0006-8993(75)90716-7. [DOI] [PubMed] [Google Scholar]
  2. Clark J. H., Anderson J. N., Peck E. J., Jr Estrogen receptor-anti-estrogen complex: atypical binding by uterine nuclei and effects on uterine growth. Steroids. 1973 Nov;22(5):707–718. doi: 10.1016/0039-128x(73)90118-9. [DOI] [PubMed] [Google Scholar]
  3. Clark J. H., Peck E. J., Jr, Anderson J. N. Oestrogen receptors and antagonism of steroid hormone action. Nature. 1974 Oct 4;251(5474):446–448. doi: 10.1038/251446a0. [DOI] [PubMed] [Google Scholar]
  4. Fox T. O. Conversion of the hypothalamic estradiol receptor to the "nuclear" form. Brain Res. 1977 Jan 28;120(3):580–583. doi: 10.1016/0006-8993(77)90414-0. [DOI] [PubMed] [Google Scholar]
  5. GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ginsburg M., Greenstein B. D., MacLusky N. J., Morris I. D., Thomas P. J. An improved method for the study of high-affinity steroid binding:-oestradiol binding in brain and pituitary. Steroids. 1974 Jun;23(6):773–792. doi: 10.1016/0039-128x(74)90053-1. [DOI] [PubMed] [Google Scholar]
  7. Ginsburg M., Maclusky N. J., Morris I. D., Thomas P. J. The specificity of oestrogen receptor in brain, pituitary and uterus. Br J Pharmacol. 1977 Mar;59(3):397–402. doi: 10.1111/j.1476-5381.1977.tb08392.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gorski J., Gannon F. Current models of steroid hormone action: a critique. Annu Rev Physiol. 1976;38:425–450. doi: 10.1146/annurev.ph.38.030176.002233. [DOI] [PubMed] [Google Scholar]
  9. Harper M. J., Walpole A. L. A new derivative of triphenylethylene: effect on implantation and mode of action in rats. J Reprod Fertil. 1967 Feb;13(1):101–119. doi: 10.1530/jrf.0.0130101. [DOI] [PubMed] [Google Scholar]
  10. Jensen E. V., DeSombre E. R. Estrogen-receptor interaction. Science. 1973 Oct 12;182(4108):126–134. doi: 10.1126/science.182.4108.126. [DOI] [PubMed] [Google Scholar]
  11. Katzenellenbogen B. S., Ferguson E. R. Antiestrogen action in the uterus: biological ineffectiveness of nuclear bound estradiol after antiestrogen. Endocrinology. 1975 Jul;97(1):1–12. doi: 10.1210/endo-97-1-1. [DOI] [PubMed] [Google Scholar]
  12. Kistner R. W. Sequential use of clomiphene citrate and human menopausal gonadotropin in ovulation induction. Fertil Steril. 1976 Jan;27(1):72–82. doi: 10.1016/s0015-0282(16)41597-9. [DOI] [PubMed] [Google Scholar]
  13. Korenman S. G. Comparative binding affinity of estrogens and its relation to estrogenic potency. Steroids. 1969 Feb;13(2):163–177. doi: 10.1016/0039-128x(69)90004-x. [DOI] [PubMed] [Google Scholar]
  14. Labhsetwar A. P. Role of estrogens in ovulation: A study using the estrogen-antagonist, I.C.I. 46,474. Endocrinology. 1970 Sep;87(3):542–551. doi: 10.1210/endo-87-3-542. [DOI] [PubMed] [Google Scholar]
  15. Lunan C. B., Klopper A. Antioestrogens. A review. Clin Endocrinol (Oxf) 1975 Sep;4(5):551–572. doi: 10.1111/j.1365-2265.1975.tb01568.x. [DOI] [PubMed] [Google Scholar]
  16. Luttge W. G., Gray H. E., Hughes J. R. Regional and subcellular [3h]estradiol localization in selected brain regions and pituitary of female mice: effects of unlabeled estradiol and various anti-hormones. Brain Res. 1976 Mar 12;104(2):273–281. doi: 10.1016/0006-8993(76)90619-3. [DOI] [PubMed] [Google Scholar]
  17. Major J. S., Green B., Heald P. J. Interactions of oestradiol-17beta and tamoxifen in the uterus of the pregnant rat. J Endocrinol. 1976 Dec;71(3):315–324. doi: 10.1677/joe.0.0710315. [DOI] [PubMed] [Google Scholar]
  18. Maurer R., Woolley D. Distribution of 3H-estradiol in clomiphene-treated and neonatally androgenized rats. Endocrinology. 1971 Jun;88(6):1281–1287. doi: 10.1210/endo-88-6-1281. [DOI] [PubMed] [Google Scholar]
  19. Mayer H. G. Experimental investigation on the effect of clomiphene on the gonadotrophin secretion of the rat pituitary. Endocrinol Exp. 1973 Sep;7(3):177–182. [PubMed] [Google Scholar]
  20. Morris I. D. Changes in brain, pituitary and uterine cytoplasmic oestrogen receptors induced by oestradiol-17beta in the ovariectomized rat. J Endocrinol. 1976 Dec;71(3):343–349. doi: 10.1677/joe.0.0710343. [DOI] [PubMed] [Google Scholar]
  21. Morris I. D., Kurl R. D. Proceedings: A selective action of clomophene upon central and peripheral oestrogen cytoplasmic receptors. J Endocrinol. 1976 Mar;68(3):29P–29P. [PubMed] [Google Scholar]
  22. Müller R. E., Wotiz H. H. Post-coital contraceptive activity and estrogen receptor binding affinity of phenolic steroids. Endocrinology. 1977 Feb;100(2):513–519. doi: 10.1210/endo-100-2-513. [DOI] [PubMed] [Google Scholar]
  23. Nagel S., Baier H., Taubert H. D. Contrasting actions of cis- and trans-clomiphene on the release of FSH and FSH-RF in the female rat. Horm Metab Res. 1970 Nov;2(6):344–348. doi: 10.1055/s-0028-1095051. [DOI] [PubMed] [Google Scholar]
  24. ROY S., GREENBLATT R. B., MAHESH V. B. EFFECTS OF CLOMIPHENE ON THE PHYSIOLOGY OF REPRODUCTION IN THE RAT. II. ITS OESTROGENIC AND ANTIOESTROGENIC ACTIONS. Acta Endocrinol (Copenh) 1964 Dec;47:657–668. doi: 10.1530/acta.0.0470657. [DOI] [PubMed] [Google Scholar]
  25. ROY S., MAHESH V. B., GREENBLATT R. B. EFFECTS OF CLOMIPHENE ON THE PHYSIOLOGY OF REPRODUCTION IN THE RAT. I. CHANGES IN THE HYPOPHYSEAL-GONADAL AXIS. Acta Endocrinol (Copenh) 1964 Dec;47:645–656. doi: 10.1530/acta.0.0470645. [DOI] [PubMed] [Google Scholar]
  26. Rinehart J. S., Ruh T. S., Ruh M. F. Anti-oestrogen action: uterine nuclear retention of the CI-628 anti-oestrogen receptor complex in vitro. Acta Endocrinol (Copenh) 1977 Feb;84(2):367–373. doi: 10.1530/acta.0.0840367. [DOI] [PubMed] [Google Scholar]
  27. Roy E. J., Wade G. N. Binding of [3-H]estradiol by brain cell nuclei and female rat sexual behavior: inhibition by antiestrogens. Brain Res. 1977 Apr 22;126(1):73–87. doi: 10.1016/0006-8993(77)90216-5. [DOI] [PubMed] [Google Scholar]
  28. Schally A. V., Carter W. H., Parlow A. F., Saito M., Arimura A., Bowers C. Y., Holtkamp D. E. Alteration of LH and FSH release in rats treated with clomiphene or its isomers. Am J Obstet Gynecol. 1970 Aug 15;107(8):1156–1167. doi: 10.1016/s0002-9378(15)30364-1. [DOI] [PubMed] [Google Scholar]
  29. Shirley B., Wolinsky J., Schwartz N. B. Effects of a single injection of an estrogen antagonist on the estrous cycle of the rat. Endocrinology. 1968 May;82(5):959–968. doi: 10.1210/endo-82-5-959. [DOI] [PubMed] [Google Scholar]
  30. Skidmore J., Walpole A. L., Woodburn J. Effect of some triphenylethylenes on oestradiol binding in vitro to macromolecules from uterus and anterior pituitary. J Endocrinol. 1972 Feb;52(2):289–298. doi: 10.1677/joe.0.0520289. [DOI] [PubMed] [Google Scholar]
  31. Terenius L. Structure-activity relationships of anti-oestrogens with regard to interaction with 17-beta-oestradiol in the mouse uterus and vagina. Acta Endocrinol (Copenh) 1971 Mar;66(3):431–447. doi: 10.1530/acta.0.0660431. [DOI] [PubMed] [Google Scholar]
  32. Whalen R. E., Gorzalka B. B. Effects of an estrogen antagonist on behavior and on estrogen retention in neural and peripheral target tissues. Physiol Behav. 1973 Jan;10(1):35–40. doi: 10.1016/0031-9384(73)90082-6. [DOI] [PubMed] [Google Scholar]

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