Estrogenic regulation of proenkephalin mRNA expression in the ventromedial hypothalamus of the adult male rat

Endogenous opioid peptides and their receptors are regulated by gonadal steroid hormones in the rat hypothalamus. Recent evidence suggests that gonadal steroids are capable of regulating the expression of proenkephalin (PE) mRNA in the ventromedial hypothalamus (VMH) of female, but not male rats. Therefore, we examined the effect of gonadectomy with or without four weeks of hormone treatment on PE mRNA expression in adult male Fisher 344 rats using quantitative in situ hybridization histochemistry. Gonadectomy reduced plasma testosterone and dihydrotestosterone (DHT) levels compared to intact rats, while subsequent estradiol (E₂) or DHT treatment increased plasma E₂ and DHT levels, respectively. Furthermore, gonadectomy reduced PE mRNA expression in the VMH, but not in the striatum nor the olfactory tubercle compared to intact rats, and this reduction was prevented in the presence of E₂, but not DHT. The results suggest that the activation of estrogen receptors normally functions to maintain the level of VMH PE mRNA expression, which is sensitive to hormonal regulation in adult male rats. Thus, gonadal steroid hormones might regulate those reproductive functions which are modulated by PE-derived opioid peptides in the male rat brain.