Effects of dehydroepiandrosterone (DHEA) on GnRH gene expression in the rat brain as studied by in situ hybridization.

Dehydroepiandrosterone (DHEA) is an adrenal androgen that is converted into potent androgens and/or estrogens in peripheral tissues. To further investigate the potential role of DHEA in reproductive functions in the rat, we have studied the effect of 2-day administration of DHEA on GnRH gene expression in brain of sham-operated and castrated animals of both sexes. In the male rat, orchiectomy induced an increase in the hybridization signal. In sham-operated animals, DHEA decreased GnRH mRNA levels induced by orchiectomy. In orchiectomized rats, DHEA also depressed the amount of mRNA levels and then reversed the increase in mRNA levels induced by orchiectomy. In female animals, as observed in the male, castration produced an increase in the hybridization signal. In both sham-operated and ovariectomized animals, DHEA administration increased mRNA levels. These data clearly indicate that DHEA administration can modify neuronal GnRH gene expression in adult rats of both sexes, the effect being inhibitory in the male and stimulating in the female. This modulation of GnRH neuronal activity, which is probably exerted following the conversion of DHEA into active sex steroids, might be at least partly responsible for modifications of the activity of the hypothalamo-pituitary-gonadal axis induced by DHEA.