TY - JOUR
T1 - Control of rat tail skin temperature regulation by estrogen receptor-beta selective ligand
AU - Opas, Evan E.
AU - Scafonas, Angela
AU - Nantermet, Pascale V.
AU - Wilkening, Robert R.
AU - Birzin, Elizabeth T.
AU - Wilkinson, Hilary
AU - Colwell, Lawrence F.
AU - Schaeffer, James M.
AU - Towler, Dwight A.
AU - Rodan, Gideon A.
AU - Schmidt, Azriel
N1 - Funding Information:
This work was funded by research and development budget of Merck & Co.
PY - 2009/9/20
Y1 - 2009/9/20
N2 - 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.
AB - 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.
KW - ERaKO
KW - Estrogen receptor alpha
KW - Estrogen receptor-beta
KW - Hormone replacement
KW - Hot flushes
KW - Tail skin temperature
KW - Thermoregulation
KW - Uterocalin
KW - Uterus
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U2 - 10.1016/j.maturitas.2009.07.007
DO - 10.1016/j.maturitas.2009.07.007
M3 - Article
C2 - 19679413
AN - SCOPUS:69549118307
SN - 0378-5122
VL - 64
SP - 46
EP - 51
JO - Maturitas
JF - Maturitas
IS - 1
ER -