Control of rat tail skin temperature regulation by estrogen receptor-beta selective ligand.
OBJECTIVE
To test the role of ERbeta in the control of estrogen-dependent thermoregulation in rats.


METHODS
Test the ability of an ERbeta-selective ligand to suppress the elevation in basal rat tail skin temperature (TST) caused by ovariectomy (OVX).


RESULTS
ERbeta-19 is a tetrahydrofluorenone ERbeta-selective ligand that displaces 0.1 nM estradiol from ERbeta with an IC50 of 1.8 nM compared to an IC50 of 141 nM for ERalpha. Like estradiol, it acts as an agonist on ERbeta-mediated transactivation and transrepression with 25- and 60-fold selectivity, respectively, over ERalpha-controlled transcription. Administration of estradiol to estrogen-depleted rats suppresses the ovariectomy-induced elevation of TST. Similar treatment of OVX rats with ERbeta-19 also results in suppression of elevated TST. However, in contrast to estradiol, ERbeta-19 does not suppress body weight, does not increase uterine weight, nor does it stimulate uterocalin biomarker expression which is under the control of ERalpha. Thus, the ERbeta-19 suppression of rat TST is mediated by ERbeta without eliciting the activity of ERalpha.


CONCLUSIONS
Estrogen-sensitive thermoregulation in ovariectomized rats can be controlled by an ERbeta-selective ligand.
Opas
Evan E
EE
Department of Molecular Endocrinology and Bone Biology, WP26A-1000, Merck Research Laboratories, West Point, PA 19486, USA.
Scafonas
Angela
A
Nantermet
Pascale V
PV
Wilkening
Robert R
RR
Birzin
Elizabeth T
ET
Wilkinson
Hilary
H
Colwell
Lawrence F
LF
Schaeffer
James M
JM
Towler
Dwight A
DA
Rodan
Gideon A
GA
Schmidt
Azriel
A
D000818:Animals; D001833:Body Temperature Regulation / Q000235:genetics* / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D004958:Estradiol / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005449:Fluorenes / Q000494:pharmacology*; D005786:Gene Expression Regulation; D008024:Ligands; D054834:Lipocalins / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012881:Skin Temperature / Q000235:genetics* / Q000502:physiology; D013623:Tail; D014599:Uterus / Q000378:metabolism
C545987:4-bromo-9a-butyl-7-hydroxy-1,2,9,9a-tetrahydro-3H-fluoren-3-one; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005449:Fluorenes; D008024:Ligands; D054834:Lipocalins; D004958:Estradiol