The antiestrogen ICI 182,780 decreases the expression of estrogen receptor-alpha but has no effect on estrogen receptor-beta and androgen receptor in rat efferent ductules

Reprod Biol Endocrinol. 2003 Oct 10:1:75. doi: 10.1186/1477-7827-1-75.

Abstract

Background: The antiestrogen ICI 182,780 has been used successfully as an alternative experimental model for the study of estrogen action in the rodent adult male reproductive tract. Although ICI 182,780 causes severe alterations in testicular and efferent ductule morphology and function, the effects on the expression of estrogen and androgen receptors in the male have not been shown.

Methods: In the present study, adult male rats were treated with ICI 182,780 for 7 to 150 days, to evaluate the time-response effects of the treatment on the pattern of ERalpha, ERbeta and AR protein expression in the efferent ductules. The receptors were localized using immunohistochemistry.

Results: ERalpha, ERbeta and AR have distinct cellular distribution in the testis and efferent ductules. Staining for ERalpha is nearly opposite of that for ERbeta, as ERalpha shows an increase in staining intensity from proximal to distal efferent ductules, whereas ERbeta shows the reverse. Androgen receptor follows that of ERalpha. ICI 182,780 caused a gradual but dramatic decrease in ERalpha expression in the testis and efferent ductules, but no change in ERbeta and AR expression.

Conclusions: The differential response of ERalpha and ERbeta proteins to ICI 182,780 indicates that these receptors are regulated by different mechanisms in the male reproductive tract.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Depression, Chemical
  • Epididymis / metabolism
  • Epididymis / ultrastructure
  • Estradiol / analogs & derivatives*
  • Estradiol / pharmacology*
  • Estrogen Receptor Modulators / pharmacology*
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Fulvestrant
  • Gene Expression Regulation / drug effects*
  • Leydig Cells / metabolism
  • Leydig Cells / ultrastructure
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Androgen / biosynthesis
  • Receptors, Androgen / genetics
  • Receptors, Estrogen / biosynthesis*
  • Receptors, Estrogen / genetics
  • Sertoli Cells / metabolism
  • Sertoli Cells / ultrastructure
  • Spermatozoa / metabolism
  • Spermatozoa / ultrastructure
  • Testis / cytology
  • Testis / drug effects*
  • Testis / metabolism

Substances

  • Estrogen Receptor Modulators
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Receptors, Androgen
  • Receptors, Estrogen
  • Fulvestrant
  • Estradiol