Calcium ion and cyclic adenosine 3',5'-monophosphate regulate proopiomelanocortin messenger ribonucleic acid levels in rat intermediate and anterior pituitary lobes.
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 microM) and cholera toxin (100 ng/ml) or the phosphodiesterase inhibitor RO 20-1724 (100 microM). 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 microM), verapamil (50 microM), and the dihydropyridine nifedipine (0.1 microM) decreased basal POMC mRNA levels, whereas the dihydropyridine BAYK 8644 (0.1 microM), 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.
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D004723:Endorphins / Q000378:metabolism; D005786:Gene Expression Regulation; D007118:Immunoassay; D008297:Male; D010902:Pituitary Gland / Q000502:physiology*; D010903:Pituitary Gland, Anterior / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013997:Time Factors; D001615:beta-Endorphin
D004723:Endorphins; D012333:RNA, Messenger; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D000242:Cyclic AMP; D002118:Calcium