Acute activation of ERα decreases food intake, meal size, and body weight in ovariectomized rats

Abstract

Santollo J, Wiley MD, Eckel LA. Acute activation of ER␣ decreases food intake, meal size, and body weight in ovariectomized rats. Am J Physiol Regul Integr Comp Physiol 293: R2194-R2201, 2007. First published October 17, 2007; doi:10.1152/ajpregu.00385.2007.-Estradiol exerts many of its actions by coupling with two nuclear estrogen receptor (ER) proteins, ER␣, and ER␤.While the acute, anorexigenic effect of estradiol appears to involve such a mechanism, the relative contributions of ER␣ and ER␤ are equivocal. To address this problem, food intake was monitored in ovariectomized (OVX) rats following acute administration of a selective ER␣ agonist (4,4Ј,4ЈЈ-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol, PPT; dose range ϭ 0 -200 g), a selective ER␤ agonist (2,3-bis(4-hydroxyphenyl)-propionitrile, DPN; dose range ϭ 0 -600 g), and a physiological (4 g) dose of estradiol benzoate (EB). While PPT-treated rats displayed dosedependent 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 g PPT (a dose of PPT that produced a similar decrease in daily food intake as 4 g 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 g 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␣ decreases food intake, body weight, and meal size in the ovariectomized rat. 4,4Ј,4ЈЈ-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol; 2,3-bis(4-hydroxyphenyl)-propionitrile; food intake; estradiol THE OVARIAN HORMONE ESTRADIOL exerts an inhibitory effect on food intake that is particularly well characterized in the rat. For example, the periovulatory increase in estradiol secretion in female rats is associated with a phasic decrease in food intake during estrus (4,8,12), and bilateral ovariectomy promotes sustained hyperphagia (33). Available data involving estradiol benzoate (EB) or progesterone replacement alone and in combination provide evidence that the hyperphagia displayed by ovariectomized (OVX) rats is mediated solely by the postsurgical decline in estradiol secretion (2, 17).Food intake is defined by the product of meal size and meal number over a given period of time. Accordingly, any change in food intake must involve a change in one or both of these parameters. Because meal size and meal number are independently controlled in the rat (32), an important first step in identifying the mechanism underlying estradiol's anorexigenic effect involved a detailed analysis of the spontaneous feeding patterns of cycling and EB-treated OVX rats. Such studies revealed that estradiol decreases food ...

Silencing steroid receptor coactivator-1 in the nucleus of the solitary tract reduces estrogenic effects on feeding and apolipoprotein A-IV expression

“…Deletion of ERα in mice blocks the anti-obesity effects of E2 replacement (41). Additionally, administration of an ERα-selective agonist (PPT), but not an ERβ-selective agonist (DPN), promotes hypophagia in OVX rats (13). Given that apoA-IV is involved in E2's anorexigenic action, we therefore hypothesized that E2 stimulates apoA-IV gene expression through ERα.…”

“…The injections occured at 1000 h (lights off from 1600 to 0400 h). The rats were fasted for 4 h before being sacrificed at the onset of dark on the 2 nd day after the final injections, based on the time when E2 exerts its most robust anorexigenic effects in OVX rats (12,13). The brains were dissected, and the NTS was micropunched for determining apoA-IV mRNA levels by quantitative real-time PCR (qPCR) (2,14).…”

Estrogens stimulate serotonin neurons to inhibit binge-like eating in mice

“…Although it has been reported that stimulation of ERβ in the brain does not regulate basal food intake (39)(40)(41), effects of ERβ signals on binge-like eating behavior cannot be excluded. Indeed, abundance of ERβ is expressed in the DRN (26).…”

Aging and estrogen alter endothelial reactivity to reactive oxygen species in coronary arterioles

“…This increase in body weight may be attributed, in part, to the loss of the anorexigenic effects of estrogen (38), and it follows that estrogen replacement results in a loss of body weight in both young and aged rats. Because endogenous estrogen levels are initially low in aged intact females, removing the remaining estrogen had an insignificant effect on both body and uterine weight.…”