Abstract
It is well established that the ovarian hormone estradiol increases the strength of multiple anorexigenic signals and, thereby, decreases food intake in the female rat. Recently, two studies provided the first evidence that estradiol also interacts with orexigenic compounds (17; 43). To further investigate this particular action of estradiol, this thesis examined whether estradiol decreases the orexigenic effects of melanin concentrating hormone (MCH), neuropeptide Y (NPY), and agouti-related protein (AgRP), three hypothalamic neuropeptides implicated in the initiation and maintenance of meals. Experiment 1 revealed three major findings: 1) estradiol treatment produces a right-ward shift in the dose response curve of the orexigenic effect of MCH in ovariectomized (OVX) rats, 2) the orexigenic effect of MCH is decreased in female rats, relative to male rats, an effect that is likely mediated by the higher circulating levels of estradiol in female rats, relative to male rats, and 3) the orexigenic effect of MCH is decreased by the peri-ovulatory increase in estradiol secretion in ovarian-intact, cycling rats. Experiment 2 revealed that estradiol treatment decreased the orexigenic effect of NPY in OVX rats. In contrast, the same regimen of estradiol treatment failed to influence the orexigenic effect of AgRP. Taken together, these findings suggest that estradiol decreases food intake, at least in part, by decreasing the orexigenic effects of MCH and NPY. Two models are proposed that provide putative mechanisms by which estradiol could decrease MCH and/or NPY signaling.
|
