meal pattern and time-course analysis of estrogen receptor agonists

Estradiol (E2) is an ovarian hormone that has a well-characterized anorexigenic effect in female animals that was originally believed to be mediated through the activation of nuclear estrogen receptors (ERs). However, recent studies from our lab and others have shown rapid anorexigenic effects after activation of membrane ERs (mERs), such as mER and G-protein coupled estrogen receptor (GPER). The comparative action of the non-selective ER agonist, estradiol benzoate (EB), and the selective ER and GPER agonists PPT and G-1, respectively, is poorly understood. In the current study, we analyzed meal patterns after acute administration of each of these agonists in OVX female Long-Evans rats. Both PPT and G-1 produced rapid decreases in food intake within 2 and 1 h, respectively, with associated decreases in the size of the first meal following drug treatment. It was also determined that EB produces a prolonged anorexigenic effect, suppressing food intake for three days beginning 12 h after drug treatment. Overall, these findings provide additional evidence that activation of mERs alone is sufficient to decrease food intake and that mER agonists produce more rapid but more transient effects than the non-selective ER agonist EB.