Calcium Ion and Cyclic Adenosine 3′5′-Monophosphate Regulate Proopiomelanocortin Messenger Ribonucleic Acid Levels in Rat Intermediate and Anterior Pituitary Lobes

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Abstract
The role of the second messengers cAMP and Ca++ in the control of proopiomelanocortin (POMC) gene expression was investigated with the use of hybridization with cloned complementary DNA probes. The effects of cAMP-related drugs on POMC messenger RNA (mRNA) levels were assessed in primary cultures of intermediate (IL) and anterior rat pituitary cells maintained in serum-free medium. 8-Bromo-cAMP (1 mM), but not 8-bromo-cGMP (1 mM), induced a 2-fold increase in IL and anterior lobe cell after 2 days of treatment. A similar increase was obtained with the adenylate cyclase-activating drugs forskolin (1 .mu.M) and cholera toxin (100 ng/ml) or the phosphodiesterase inhibitor RO 20-1724 (100 .mu.M). aT 48 h, all these treatments had increased .beta.-endorphin accumulation in the medium and transiently decreased the cellular .beta.-endorphin content in IL cells, suggesting a parallel effect of cAMP-related drugs on secretion and biosynthesis. Incubating the cells with the Ca++ channel antagonists D600 (50 .mu.M), verapamil (50 .mu.M), and the dihydropyridine nifedipine (0.1 .mu.M) decreased basal POMC mRNA levels, whereas the dihydropyridine BAYK 8644 (0.1 .mu.M), which activates the Ca++ channel, increased POMC mRNA levels after 2 days. In addition, nifedipine decreased the stimulatory effect of forskolin, whereas BAYK 8644 further stimulated the forskolin-increased POMC mRNA levels in IL cells. We conclude that both Ca++ and cAMP may regulate the gene expression of POMC.