EFFECTS OF DEHYDROEPIANDROSTERONE (DHEA) ON PITUITARY PROLACTIN AND ARCUATE NUCLEUS NEURON TYROSINE-HYDROXYLASE MESSENGER-RNA LEVELS IN THERAT

It is well documented that dehydroepiandrosterone (DHEA), an adrenal a ndrogen, is converted into potent androgens and/or estrogens in periph eral tissues. Since sex steroids are involved in the regulation of pro lactin (PRL) secretion, we have studied the effect of DHEA administrat ion on PRL mRNA levels in both adult male and female rats. Since tuber oinfundibular dopaminergic (TIDA) neurons are involved in the negative regulation of PRL, we have also evaluated the effects of DHEA on the genetic expression of tyrosine hydroxylase (TH), the limiting enzyme i n catecholamine biosynthesis in TIDA neurons. Sham-operated and castra ted animals of both sexes received during 2 days DHEA at the dose of 6 mg/kg/day, starting on the first day after castration. PRL and TH mRN A levels were measured by quantitative in situ hybridization. In the m ale rat, orchiectomy performed 3 days earlier did not modify PRL mRNA levels. DHEA administration increased the hybridization signal in both sham-operated and orchiectomized animals. In the female, ovariectomy decreased PRL mRNA levels and, as observed in the male, DHEA treatment induced an increase in the hybridization signal in both control and o variectomized rats. In TIDA neurons, castration increased TH mRNA leve ls as evaluated by number of grains over labelled neurons and the numb er of TH-labelled cells per section in both male and female animals. I n both sham-operated male rats and orchiectomized animals, DHEA decrea sed the hybridization signal, In the female, DHEA administration compl etely prevented the increase in TH mRNA levels due to ovariectomy. In sham-operated female rats, the treatment had no effect. These data cle arly indicate that in both male and female rats DHEA exerts an estroge nic influence on both PRL and TH gene expression. Although these in vi vo experiments do not allow to establish whether the stimulation of PR L gene expression is due to an action of the steroid on the pituitary or at the hypothalamic level or alternatively at both sites, it is lik ely that one of the mechanisms of action of DHEA might be related to a decrease in dopamine release following a depression of TIDA neuron ac tivity.