Despite the fact that eating disorders are more prevalent in women than in men, the mechanism driving this sex difference is poorly understood. While environmental and cultural factors likely contribute to the greater prevalence of eating disorders in women, it is becoming increasing clear that biological factors may also play a key role. In recent years, the ovarian hormone estradiol, which exerts a potent anorexigenic effect in variety of species including humans, has emerged as a putative, biological risk factor for eating disorders in general, and anorexia nervosa in particular. A crucial first step in understanding how estradiol may contribute to eating disorders is to determine how it affects the normal controls of food intake in healthy animals. Available evidence suggests that the anorexigenic effect of estradiol is mediated indirectly through interactions with other key elements of the neural and endocrine systems controlling ingestive behavior. While it is well established that estradiol increases the female rat's sensitivity to anorexigenic (appetite suppressing) peptides and neurotransmitter systems, my preliminary data suggest that estradiol is also capable of decreasing the female rat's sensitivity to an orexigenic (appetite stimulating) neuropeptide, melanin-concentrating hormone (MCH). In the present application, I propose to examine the neural mechanisms underlying estradioPs ability to decrease MCH-induced feeding. My working hypothesis is that estradiol acts via nuclear estrogen receptors (ERs) to decrease MCH signaling and, as a consequence, decreases food intake. Using single-label immunohistochemistry, I will determine whether estradiol decreases MCH or MCH receptor (MCHR1) protein expression in brain regions implicated in the control of food intake. I will also combine site-specific infusions of estraidol with ventricular infusions of MCH in order to identify brain region(s) in which estradiol acts to decrease MCH-induced feeding. Finally, I will investigate whether ERs are expressed within the same neurons that express MCH and MCHR1. This series of studies has the potential to increase our understanding of the mechanism underlying estradiol's anorexigenic effect and this knowledge may ultimately reveal how estradiol functions as a risk factor for certain eating-related disorders. In completing this research, I will learn new techniques and further my professional development, allowing me to reach my ultimate goal of becoming an independent scientist.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS062667-03
Application #
7809541
Study Section
Special Emphasis Panel (ZRG1-F02A-H (20))
Program Officer
Gnadt, James W
Project Start
2008-06-13
Project End
2010-08-31
Budget Start
2010-06-13
Budget End
2010-08-31
Support Year
3
Fiscal Year
2010
Total Cost
$6,406
Indirect Cost
Name
Florida State University
Department
Social Sciences
Type
Schools of Arts and Sciences
DUNS #
790877419
City
Tallahassee
State
FL
Country
United States
Zip Code
32306
Santollo, J; Eckel, L A (2013) Oestradiol decreases melanin-concentrating hormone (MCH) and MCH receptor expression in the hypothalamus of female rats. J Neuroendocrinol 25:570-9
Rivera, Heidi M; Santollo, Jessica; Nikonova, Larissa V et al. (2012) Estradiol increases the anorexia associated with increased 5-HT(2C) receptor activation in ovariectomized rats. Physiol Behav 105:188-94
Eckel, Lisa A (2011) The ovarian hormone estradiol plays a crucial role in the control of food intake in females. Physiol Behav 104:517-24
Santollo, Jessica; Torregrossa, Ann-Marie; Eckel, Lisa A (2011) Estradiol acts in the medial preoptic area, arcuate nucleus, and dorsal raphe nucleus to reduce food intake in ovariectomized rats. Horm Behav 60:86-93
Santollo, Jessica; Katzenellenbogen, Benita S; Katzenellenbogen, John A et al. (2010) Activation of ER? is necessary for estradiol's anorexigenic effect in female rats. Horm Behav 58:872-7
Santollo, Jessica; Eckel, Lisa A (2009) Effect of a putative ERalpha antagonist, MPP, on food intake in cycling and ovariectomized rats. Physiol Behav 97:193-8