Estradiol and the control of feeding behavior.

This review lays out the evidence for the role of E2 in homeostatic and hedonic feeding across several species. While significant effort has been expended on homeostatic feeding research, more studies for hedonic feeding need to be conducted (i.e. are there increases in meal size and enhanced motivation to natural food rewards). By identifying the underlying neural circuitry involved, one can better delineate the mechanisms by which E2 influences feeding behavior. By utilizing more selective neural targeting techniques, such as optogenetics, significant progress can be made toward this goal. Together, behavioral and physiological techniques will help us to better understand neural deficits that can increase the risk for obesity in the absence of E2 (menopause) and aid in developing therapeutic strategies.

Ovarian steroids increase spinogenetic proteins in the macaque dorsal raphe.

Dendritic spines are the basic structural units of neuronal plasticity. Intracellular signaling cascades that promote spinogenesis have centered on RhoGTPases. We found that ovarian steroids increase gene expression of RhoGTPases [Ras homolog gene family member A (RhoA), cell division control protein 42 homolog (Cdc42), and ras-related C3 botulinum toxin substrate (Rac)] in laser-captured serotonin neurons. We sought to confirm that the increases observed in gene expression translate to the protein level. In addition, a preliminary study was conducted to determine whether an increase in spines occurs via detection of the spine marker protein, postsynaptic density-95 (PSD-95). Adult ovariectomized (Ovx) monkeys were treated with estradiol (E), progesterone (P), or E+P for 1 month. Sections through the dorsal raphe nucleus were immunostained for RhoA and Cdc42 (n=3-4/group). The number and positive pixel area of RhoA-positive cells and the positive pixel area of Cdc42-positive fibers were determined. On combining E- and E+P-treated groups, there was a significant increase in the average and total cell number and positive pixel area of RhoA-positive cells. E, P, and E+P treatments, individually or combined, also increased the average and total positive pixel area of Cdc42-positive fibers. With remaining sections from two animals in each group, we conducted a preliminary examination of the regulation of PSD-95 protein expression. PSD-95, a postsynaptic scaffold protein, was examined with immunogold silver staining (n=2/group), and the total number of PSD-95-positive puncta was determined with stereology across four levels of the dorsal raphe. E, P, and E+P treatment significantly increased the total number of PSD-95-positive puncta. Together, these findings indicate that ovarian steroids act to increase gene and protein expression of two pivotal RhoGTPases involved in spinogenesis and preliminarily indicate that an increased number of spines and/or synapses result from this action. Increased spinogenesis on serotonin dendrites would facilitate excitatory glutamatergic input and in turn, increase serotonin neuronal activity throughout the brain.