Regulation of the pro-opiomelanocortin mRNA levels in rat pituitary by dopaminergic compounds.

Abstract

Dopamine-containing neurons directly innervate the intermediate lobe of the pituitary and dopaminergic compounds exert inhibitory effects on the secretion and the content of a-melanocyte-stimulating hormone and P-endorphin in this tis-sue. In this study, we have investigated the effects of dopamine receptor agonists and antagonists on the level of pro-opiomelanocortin (POMG) mRNA in rat pituitary. RNAs isolated from neurointermediate pituitary (NIP) or anterior pituitary were spotted on nitrocellulose filters and the levels of POMC mRNA were quantified by hybridization to a POMC-specific complementary DNA probe coupled with autoradiography and densitometry. Administration of a dopamine receptor antagonist, haloperidol (2 mg/kg per day), to adult female rats resulted in a 3-to 5-fold increase in POMC mRNA level in the NIP. Treatment with the dopamine agonist 2-Br-a-ergocryptine (1 mg/kg per day) decreased significantly the content of POMC mRNA in the NIP. These drugs had no apparent effect on the POMC mRNA levels in the anterior pituitary. The effect of haloperidol and ergocryptine on POMC mRNA in the NIP is time-and dose-dependent. The elevation of POMC mRNA content in the NIP by haloperidol can be observed as early as 6 hr after treatment. These effects of dopaminergic compounds can also be demonstrated in adult male and ovariectomized female rats. The (-endorphin content of the NIP, as measured by radioimmunoassay, and the de novo synthesis of POMC, as determined by radioactive amino acid labeling and two-dimensional gel electrophoresis analysis, also show negative regulation by dopaminergic compounds.The monoamine neurotransmitter dopamine and its agonists have been shown to inhibit the release of ca-melanocyte-stimulating hormone (a-MSH) and ,B-endorphin, two pro-opiomelanocortin (POMC)-derived peptides, from the intermediate lobe (IP) of the rat pituitary (1-3). Dopamine antagonists, such as haloperidol, stimulate the release of a-MSH and ,B-endorphin (3,4). These effects on POMC-derived peptide secretion from the IP appear to be mediated through a D2 dopamine receptor on the IP melanotroph (for a review, see ref. 5). Dopamine-containing synaptic endings had been identified directly in the rat IP, suggesting direct neural control of IP POMC secretion (6). In the rat pituitary anterior lobe (AP), a tissue that also synthesizes and secretes POMC-derived peptides, dopaminergic agonists and antagonists have not been shown to have similar effects on POMC peptide secretion (1,7,8).Recently, it has been shown that in addition to having effects on POMC peptide secretion, dopaminergic compounds can also change IP content of POMC peptides (3, 9). Chronic treatment of the rat with dopamine agonists or antagonists either decreases or increases, respectively, the amount of radioimmunoactive ,3endorphin or a-MSH in the IP. Such observations would suggest.that these drugs have effects on POMC synthesis parallel to their effects on secretion. Indeed, a very recent study by Hollt et al. showed that chronic (7 day) ...

Regulation of bioactive β‐endorphin processing in rat pars intermedia

“…This is consistent with in vivo studies in which ergocryptine has been shown to decrease the concentration of POMC mRNA [16] and the level of intracellular ,&endorphin immunoreactivity [ 171 in the pars intermedia. In the presence of the dopaminergic agents, however, the reduced rates of POMC synthesis are accompanied by reduced rates of secretion and the ,&endorphin-related peptides remaining in the cells may be more exposed to enzyme modulation, resulting in increased proteolysis and acetylation.…”

Effects of Chronic Treatment of Rats with Dopamine Receptor Drugs on the Post‐Translational Processing of Beta‐Endorphin in the Neurointermediate Lobe of the Pituitary Gland

“…The observation that the treatments caused parallel changes in content and release, indicates that they had affected the synthesis of endorphins as well as the release, which is in line with many reports (16,17,19,20,23).…”

Pituitary cell phenotypes involve cell-specific Pit-1 mRNA translation and synergistic interactions with other classes of transcription factors.

“…Roberts, Mt. Sinai School of Medicine; see Chen et al 1983). Pit-1 RNA probes were synthesized from pBluescript SK-based vectors (Stratagene).…”