Metabolic asymmetry in the hypothalamic regulation of food-intake and reproductive processes in male and female rats.

Abstract

The hypothalamus is the highest center and the main crossroad of numerous homeostatic regulatory pathways including reproduction and energy metabolism. Histologically, the left and right hypothalamic sides are symmetrical, still, it has been considered as an unpaired midline structure, in which the two sides regulate exactly the same biological functions. It has been known for higher, morphologically also symmetric brain areas that usually the left and right sides have distinct physiological roles providing a solution for the “ergonomic” use of brain resources. The main goal of this study was to investigate asymmetry in the hypothalamic functions such as the regulation of estrous cycle and food-intake. In the hypothalamus, gender-specific functions seem to lie on the grounds of gender-indifferent anatomy. Therefore, it was reasonable to examine a general functional, instead of structural, parameter to test the possibility that the hypothalamus might, indeed, act in a lateralized manner in one or more of its functions. Such a parameter is the mitochondrial respiration. In order to clarify the above-mentioned goals, we investigated the metabolic asymmetry between the left and right hypothalamic sides of male and female rats by measuring mitochondrial respiration rates, a parameter that reflects the intensity of cell and tissue metabolism. In our first experiment, we used intact, normal cycling female rats sacrificed in different phases of the estrous cycle. In experiment 2 and 3, gonadectomized male and female animals were used. The effects of reproductive (estrous phase, ovariectomy, ovariectomy plus estrogen treatment) and hunger signals (ad libitum fed, fasted) were analyzed in various states of mitochondrial respiration. Results revealed estrous phase-, estrogen- (females) and satiety state-dependent (males and females) metabolic differences between the two hypothalamic hemispheres of rats. It appears that in the regulation of female reproduction, predetermined, strongly estrogen-related sidedness exists with a right sided dominance. On the other hand, asymmetric, side-linked mechanisms seem to drive the feeding circuitries in males and females as well. A dynamic balance exists between the hypothalamic hemispheres in which both sides are able to react to orexigenic, as well as anorexigenic signals, but the left side dominates in orexigenic, while the right one in anorexigenic milieu. Furthermore, by comparing the metabolic profile of male and female hypothalami, we could also describe some fundamental gender-related differences showing that the hypothalamic lateralization in males is mostly related to food-intake, while in females, reproductive processes seem to have a higher impact on the hypothalamic asymmetry, at least under the present experimental conditions. This study changes our current view on the regulation of female reproduction and food-intake, and provides new perspectives for the better understanding of these hypothalamus-driven physiological processes.