Acute activation of ER alpha decreases food intake, meal size, and body weight in ovariectomized rats.
Estradiol exerts many of its actions by coupling with two nuclear estrogen receptor (ER) proteins, ER alpha, and ER beta. While the acute, anorexigenic effect of estradiol appears to involve such a mechanism, the relative contributions of ERalpha and ERbeta are equivocal. To address this problem, food intake was monitored in ovariectomized (OVX) rats following acute administration of a selective ER alpha agonist (4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol, PPT; dose range = 0-200 microg), a selective ER beta agonist (2,3-bis(4-hydroxyphenyl)-propionitrile, DPN; dose range = 0-600 microg), and a physiological (4 microg) dose of estradiol benzoate (EB). While PPT-treated rats displayed dose-dependent decreases in daily food intake and body weight, neither of these measures was influenced by any dose of DPN. In addition, DPN failed to modulate the anorexigenic effect of PPT when the two ER agonists were coadministered. Meal pattern analysis revealed that the anorexigenic effect of 75 microg PPT (a dose of PPT that produced a similar decrease in daily food intake as 4 microg EB) was mediated by a decrease in meal size, not meal number. Thus, PPT, like EB and endogenous estradiol, decreases food intake by selectively affecting the controls of meal size. The finding that acute administration of 75 microg PPT failed to induce a conditioned taste aversion suggests that the anorexigenic effect of this dose of PPT is not secondary to malaise. Taken together, our findings demonstrate that selective activation of ER alpha decreases food intake, body weight, and meal size in the ovariectomized rat.
Santollo
Jessica
J
Program in Neuroscience, Florida State Univ., Tallahassee, FL 32306-1270, USA.
Wiley
Mathew D
MD
Eckel
Lisa A
LA
D000818:Animals; D001066:Appetite / Q000187:drug effects / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects / Q000502:physiology*; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000187:drug effects / Q000378:metabolism*; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D009570:Nitriles / Q000008:administration & dosage; D010052:Ovariectomy; D010636:Phenols; D011720:Pyrazoles / Q000008:administration & dosage; D051381:Rats; D020332:Rats, Inbred LEC; D015431:Weight Loss / Q000187:drug effects / Q000502:physiology*; D011422:Propionates
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D009570:Nitriles; D010636:Phenols; D011720:Pyrazoles; C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D011422:Propionates; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol