Role of dopamine in the regulation of proopiomelanocortin (POMC) mRNA levels in the arcuate nucleus and pituitary gland of the female rat as studied by in situ hybridization.

The effects of the dopaminergic antagonist haloperidol (HAL) as well as the D2 dopamine receptor agonist bromocriptine (BRO) on proopiomelanocortin (POMC) mRNA levels in the female rat arcuate nucleus and pituitary were investigated by quantitative in situ hybridization. Since we had already shown that sex steroids could induce a decrease in POMC mRNA levels in the arcuate nucleus of castrated rats, the involvement of the dopaminergic system in the inhibitory effect of estradiol (E2) was also investigated. In situ hybridization was performed on paraformaldehyde-fixed cryostat sections through the arcuate nucleus and whole pituitary gland using a 35S-labelled cDNA probe encoding for POMC. In the arcuate nucleus of intact animals, a 14-day treatment with BRO increased by 54% the number of silver grains/unit of surface of labelled neurons while HAL decreased by 30% the value of this parameter. Hypophysectomy which induced a 20% decrease in the hybridization signal could not prevent the effects of BRO or HAL. Ovariectomy performed 14 days earlier increased by 20% the number of silver grains while a 14-day treatment of ovariectomized animals with E2 decreased the hybridization signal by 32%. On the other hand, the concomitant administration of HAL and E2 did not induce significant variations in POMC mRNA levels compared to those obtained following HAL administration, but slightly decreased the hybridization signal by 20% compared to that induced by E2 alone. In the intermediate lobe of the pituitary, BRO markedly depressed (30% of control values) and HAL increased by 50% the levels of POMC mRNA. The present data clearly demonstrate that POMC mRNA levels are differently regulated by dopamine in the intermediate lobe of the pituitary and the arcuate nucleus and that the effects of BRO and HAL on arcuate POMC mRNA are not mediated by the pituitary gland. They do not allow to draw any definite conclusion about the possible involvement of the dopaminergic system in the inhibitory role of E2 on POMC gene regulation.