Sex-specific effects of dehydroepiandrosterone (DHEA) on glucose metabolism in the CNS

- DHEA decreased glucose uptake in the cerebral cortex of male rats, but had no effect on glucose uptake in the olfactory bulb or hippocampus, and in females.
- DHEA increased glucose oxidation in the cerebral cortex, olfactory bulb and hypothalamus in male rats, and in cerebral cortex and olfactory bulb in female.
- DHEA increased the glycogen content in the cerebral cortex and olfactory bulb in male.
- Males have higher uptake of glucose than females in response to DHEA in cortex, hippocampus and hypothalamus.
- The increased glucose oxidation in cerebral cortex in both sexes was more pronounced in females than in males.

DHEA is a neuroactive steroid, due to its modulatory actions on the central nervous system (CNS). DHEA is able to regulate neurogenesis, neurotransmitter receptors and neuronal excitability, function, survival and metabolism. The levels of DHEA decrease gradually with advancing age, and this decline has been associated with age related neuronal dysfunction and degeneration, suggesting a neuroprotective effect of endogenous DHEA. There are significant sex differences in the pathophysiology, epidemiology and clinical manifestations of many neurological diseases. The aim of this study was to determine whether DHEA can alter glucose metabolism in different structures of the CNS from male and female rats, and if this effect is sex-specific. The results showed that DHEA decreased glucose uptake in some structures (cerebral cortex and olfactory bulb) in males, but did not affect glucose uptake in females. When compared, glucose uptake in males was higher than females. DHEA enhanced the glucose oxidation in both males (cerebral cortex, olfactory bulb, hippocampus and hypothalamus) and females (cerebral cortex and olfactory bulb), in a sex-dependent manner. In males, DHEA did not affect synthesis of glycogen, however, glycogen content was increased in the cerebral cortex and olfactory bulb. DHEA modulates glucose metabolism in a tissue-, dose- and sex-dependent manner to increase glucose oxidation, which could explain the previously described neuroprotective role of this hormone in some neurodegenerative diseases.