Manipulations of metabolic fuel availability alter estrous behavior and neural estrogen receptor immunoreactivity in Syrian hamsters.

Decreases in metabolic fuel utilization caused by food deprivation, diabetes, or treatment with metabolic inhibitors have been shown to suppress steroid-induced estrous behavior in ovariectomized Syrian hamsters. These same manipulations also caused a decrease in the number of detectable estrogen-receptor immunoreactive (ERIR) cells in the ventromedial hypothalamus (VMH) and the adjacent area lateral to it (VLH) in ovariectomized hamsters. Forty-eight hours of food deprivation or treatment with pharmacological blockers of glycolysis (2-deoxy-D-glucose) and fatty acid oxidation (methyl palmoxirate) decreased the number of detectable ERIR cells in the VMH/VLH. However, neither inhibitor given alone was sufficient to affect the number of detectable ERIR cells in the VMH/VLH, even when given in much higher doses. Therefore, the number of ERIR cells in the VMH/VLH, like steroid-induced estrous behavior, responds only to a combination of glucoprivation and lipoprivation and not to either alone. The effects of metabolic fuel restriction are not due to a general suppression of neural ERIR, because food deprivation or treatment with 2-deoxy-D-glucose and methyl palmoxirate actually increased the number of detectable ERIR cells in the medial preoptic area (mPOA) and had no effect in the nucleus of the solitary tract. Lesions destroying the area postrema (AP) prevented the decrease in ERIR cells in the VMH/VLH and the inhibition of estrous behavior caused by fuel restriction. However, AP lesions did not alter the effects of metabolic inhibitors on ERIR in the mPOA. On the other hand, subdiaphragmatic vagotomy abolished the effects of metabolic inhibitors on mPOA ERIR, but did not affect either lordosis or VMH/VLH ERIR. These results suggest that the suppression of estrous behavior induced by metabolic fuel restriction is at least in part due to a decrease in the number of ERIR neurons in the VMH/VLH. In addition, the estrogen-sensitive neurons in the VMH/VLH and mPOA receive metabolic cues via different neural pathways. The AP, but not vagus nerves, is required for ERIR neurons in the VMH/VLH to detect fuel availability; the vagus nerves, but not the AP, are necessary for estrogen-binding neurons in the mPOA to detect visceral information.