AROMATIZATION IS NOT REQUIRED FOR ANDROGEN-INDUCED CHANGES IN PROOPIOMELANOCORTIN GENE-EXPRESSION IN THE HYPOTHALAMUS

Testosterone regulation of POMC mRNA and peptide levels has been previously demonstrated in the medial basal hypothalamus (MBH) of the rat. Although both dihydrotestosterone (DHT) and estradiol are known to affect POMC peptide levels in the MBH, it is unclear if the effects of testosterone on POMC gene expression are due to conversion by aromatization to estradiol or due to independent androgen actions. We have therefore compared the effects of the nonaromatizable androgen DHT and estradiol on POMC gene expression and beta-endorphin (beta-EP) levels in the MBH of castrated male rats. We have also examined the effect of the dopamine agonist, pergolide, on POMC in the DHT and estradiol treated animals in light of previous studies in female rats. In the first study POMC mRNA in the MBH, as measured by a solution hybridization assay, was 0.85 +/- 0.07 pg/mu g RNA 3 weeks after castration and decreased to 0.64 +/- 0.07 pg and 0.65 +/- 0.07 pg in the DHT treated rats with and without pergolide (P < 0.05). In the second study the mean POMC mRNA concentration in the MBH was 0.95 +/- 0.10 pg/mu g RNA and decreased to 0.68 +/- 0.06 pg and 0.70 +/- 0.08 pg in the estradiol treated rats with and without pergolide (P < 0.05). In both studies significant changes in beta-EP peptide levels paralleled the changes in POMC mRNA levels. We conclude that both androgens and estrogens can affect POMC mRNA levels in the male rat. The effectiveness of DHT in this respect demonstrates that aromatization is not required for androgen actions on POMC and indicates that there is independent androgen regulation of POMC gene expression in the hypothalamus.