Activation of ERα is necessary for estradiol's anorexigenic effect in female rats

Abstract

While there is considerable evidence that the ovarian hormone estradiol reduces food intake in female rats, it is unclear which estrogen receptor (ER) subtype, ERα or ERβ, mediates this effect. While several studies have demonstrated that activation of ERα, but not ERβ, is sufficient to reduce food intake in ovariectomized (OVX) rats, there are limited data regarding which receptor subtype is necessary. Here we used the selective ERα and ERß antagonists, MPrP and PHTPP, respectively, to investigate this question. We found that antagonism of ERα, but not ERβ, prevented the decrease in food intake following acute administration of estradiol in OVX rats. In addition, antagonism of ERα prevented the estrous-related, phasic reduction in food intake that occurs in response to the rise in circulating levels of estradiol in cycling rats. We conclude that activation of ERα is necessary for the anorexigenic effects of exogenous and endogenous estradiol in female rats.

Figure 1

Food intake in OVX rats was not influenced by blockade of either ERα or ERβ Treatment with either MPrP, an ERα antagonist (A) or PHTTP, an ERβ antagonist (B), failed to alter food intake during the 24-h period following drug treatment.

Figure 2

Blockade of ERα, but not ERβ, prevented the anorexigenic effect of estradiol benzoate (EB) in OVX rats. Food intake was monitored for 24 h beginning 24 h following treatment with vehicle, EB, or EB co-administered with either MPrP, an ERα antagonist, or PHTPP, an ERβ antagonist. (A) The EB-induced reduction in food intake was blocked by MPrP. (B) Administration of EB alone, and EB in combination with PHTPP, produced similar decreases in food intake, relative to that observed following vehicle treatment. *Less than vehicle, P < 0.01.

Figure 3

Blockade of ERα prevented the estrous-related decrease in food intake in cycling rats. Female rats received one injection of either vehicle or MPrP just prior to the dark phase of proestrous and a second injection of the same compound 12 h later. Drug treatment was administered in a counterbalanced manner across two consecutive estrous cycles. Following vehicle treatment, rats displayed a phasic reduction in food during estrus (E) compared to diestrus 2 (D2). This E-related decrease in food intake was blocked in rats pre-treated with MPrP, an ERα antagonist. *Less than all other groups, P < 0.01.