Female rats are more susceptible to metabolic effects of dehydroepiandrosterone treatment.

Dehydroepiandrosterone (DHEA) is a steroid hormone that presents several effects on metabolism; however, most of the studies have been performed on male animals, while few authors have investigated possible sex differences regarding the metabolic effects of DHEA. Therefore, the aim of this study was to evaluate the effect of different doses of DHEA on metabolic parameters of male and ovariectomized female Wistar rats. Sex differences were found in the metabolism of distinct substrates and in relation to the effect of DHEA. In respect to the glucose metabolism in the liver, the conversion of glucose to CO2 and the synthesis of lipids from glucose were 53% and 33% higher, respectively, in males. Also, DHEA decreased hepatic lipogenesis only in females. Regarding the hepatic glycogen synthesis pathway, females presented 73% higher synthesis than males, and the effect of DHEA was observed only in females, where it decreased this parameter. In the adipose tissue, glucose uptake was 208% higher in females and DHEA decreased this parameter. In the muscle, glucose uptake was 168% higher in females and no DHEA effect was observed. In summary, males and females present a different metabolic profile, with females being more susceptible to the metabolic effects of DHEA.

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

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.