Differential Effects of Haloperidol on the Rat Pituitary: Decreased Biosynthesis, Processing and Release of Anterior Lobe Pro-Opiomelanocortin

Abstract

The effects of chronic haloperidol treatment on pro-opiomelanocortin (POMC) synthesis, processing, and release in the anterior (AL) and intermediate (IL) lobes of the rat pituitary were studied. In the IL, 14 days of haloperidol administration promoted an increase in the level of POMC mRNA, and a corresponding elevation of levels of beta-endorphin (beta E), alpha-melanocyte-stimulating hormone (MSH), and gamma 3 MSH. In the AL, a reduction of POMC mRNA as well as immunoreactive beta E, adrenocorticotropin (ACTH), and gamma 3 MSH was observed. Column chromatography revealed that this treatment promoted an apparent alteration of POMC processing in AL: the conversion of larger, precursor-sized peptides to smaller, more-processed forms was relatively inhibited. Circulating levels of both N-acetyl-beta E and corticosterone were elevated following haloperidol challenge in drug-naive animals. Resting plasma levels of both, however, were not changed following chronic haloperidol treatment. Pituitary culture studies demonstrated that chronic haloperidol treatment increased the releasability of IL-derived products, while simultaneously decreasing the releasability of those products from the AL. These results suggest that pituitary POMC biosynthesis, processing and release are under at least partial dopaminergic control in both the IL and the AL of the pituitary, but by different mechanisms; chronic haloperidol treatment upregulates the POMC system in IL, but downregulates it in AL, despite similarities of the responses of both lobes to acute haloperidol challenge.