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

• Published in: Maturitas Vol. 64; no. 1; pp. 46 - 51
• Main Authors: Opas, Evan E, Scafonas, Angela, Nantermet, Pascale V, Wilkening, Robert R, Birzin, Elizabeth T, Wilkinson, Hilary, Colwell, Lawrence F, Schaeffer, James M, Towler, Dwight A, Rodan, Gideon A, Schmidt, Azriel
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 20.09.2009
• Subjects: Animals; Body Temperature Regulation - genetics; Body Temperature Regulation - physiology; Body Weight - drug effects; ERaKO; Estradiol - genetics; Estradiol - metabolism; Estradiol - pharmacology; Estrogen receptor alpha; Estrogen Receptor alpha - genetics; Estrogen Receptor alpha - metabolism; Estrogen Receptor beta - agonists; Estrogen Receptor beta - genetics; Estrogen Receptor beta - metabolism; Estrogen receptor-beta; Female; Fluorenes - pharmacology; Gene Expression Regulation; Hormone replacement; Hot flushes; Internal Medicine; Ligands; Lipocalins - metabolism; Obstetrics and Gynecology; Organ Size - drug effects; Ovariectomy; Rats; Rats, Sprague-Dawley; Skin Temperature - genetics; Skin Temperature - physiology; Tail; Tail skin temperature; Thermoregulation; Uterocalin; Uterus; Uterus - metabolism; Hot flushes; Hormone replacement; Uterus; Thermoregulation; Estrogen receptor alpha; Estrogen receptor-beta; ERaKO; Uterocalin; Tail skin temperature
• ISSN: 0378-5122; 1873-4111
• DOI: 10.1016/j.maturitas.2009.07.007

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.