Control of rat tail skin temperature regulation by estrogen receptor-beta selective ligand

Evan E. Opas, Angela Scafonas, Pascale V. Nantermet, Robert R. Wilkening, Elizabeth T. Birzin, Hilary Wilkinson, Lawrence F. Colwell, James M. Schaeffer, Dwight A. Towler, Gideon A. Rodan, Azriel Schmidt

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Objective: To test the role of ERβ in the control of estrogen-dependent thermoregulation in rats. Methods: Test the ability of an ERβ-selective ligand to suppress the elevation in basal rat tail skin temperature (TST) caused by ovariectomy (OVX). Results: ERβ-19 is a tetrahydrofluorenone ERβ-selective ligand that displaces 0.1 nM estradiol from ERβ with an IC50 of 1.8 nM compared to an IC50 of 141 nM for ERα. Like estradiol, it acts as an agonist on ERβ-mediated transactivation and transrepression with 25- and 60-fold selectivity, respectively, over ERα-controlled transcription. Administration of estradiol to estrogen-depleted rats suppresses the ovariectomy-induced elevation of TST. Similar treatment of OVX rats with ERβ-19 also results in suppression of elevated TST. However, in contrast to estradiol, ERβ-19 does not suppress body weight, does not increase uterine weight, nor does it stimulate uterocalin biomarker expression which is under the control of ERα. Thus, the ERβ-19 suppression of rat TST is mediated by ERβ without eliciting the activity of ERα. Conclusion: Estrogen-sensitive thermoregulation in ovariectomized rats can be controlled by an ERβ-selective ligand.

Original languageEnglish (US)
Pages (from-to)46-51
Number of pages6
JournalMaturitas
Volume64
Issue number1
DOIs
StatePublished - Sep 20 2009

Keywords

  • ERaKO
  • Estrogen receptor alpha
  • Estrogen receptor-beta
  • Hormone replacement
  • Hot flushes
  • Tail skin temperature
  • Thermoregulation
  • Uterocalin
  • Uterus

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Obstetrics and Gynecology

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  • Cite this

    Opas, E. E., Scafonas, A., Nantermet, P. V., Wilkening, R. R., Birzin, E. T., Wilkinson, H., Colwell, L. F., Schaeffer, J. M., Towler, D. A., Rodan, G. A., & Schmidt, A. (2009). Control of rat tail skin temperature regulation by estrogen receptor-beta selective ligand. Maturitas, 64(1), 46-51. https://doi.org/10.1016/j.maturitas.2009.07.007