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Endocrinology, Vol 119, 2840-2847, Copyright © 1986 by Endocrine Society

ARTICLES

Calcium ion and cyclic adenosine 3',5'-monophosphate regulate proopiomelanocortin messenger ribonucleic acid levels in rat intermediate and anterior pituitary lobes

JP Loeffler, N Kley, CW Pittius and V Hollt

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.


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I. Murakami, S. Takeuchi, T. Kudo, S. Sutou, and S. Takahashi
Corticotropin-releasing hormone or dexamethasone regulates rat proopiomelanocortin transcription through Tpit/Pitx-responsive element in its promoter
J. Endocrinol., May 1, 2007; 193(2): 279 - 290.
[Abstract] [Full Text] [PDF]


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