Calcium-independent and calcium-dependent mechanisms regulate corticotropin-releasing factor-stimulated proopiomelanocortin peptide secretion and messenger ribonucleic acid production.
We have evaluated the role of calcium in basal and secretagogue-stimulated release of beta-endorphin and PRL and the levels of their respective mRNAs in primary cultured rat anterior pituitary cells. Treatment of anterior pituitary cells with the calcium channel blocker methoxyverapamil (D600; 10 microM) or with calcium-free medium for 1 h did not alter the basal release of beta-endorphin and only partially blocked CRF (10 nM)-stimulated beta-endorphin release. In contrast to these effects of D600 or calcium-free medium on corticotrophs, both of these test conditions decreased basal secretion of PRL from lactotrophs by 50-70% and completely blocked forskolin (10 microM)-stimulated PRL secretion. Although omission of calcium from the culture medium caused a 50% decrease in basal levels of both proopiomelanocortin (POMC) and PRL mRNA, treatment of cells with D600 did not significantly alter the basal levels of POMC or PRL mRNA. Treatment of cells with D600 partially blocked CRF-stimulated elevation of POMC mRNA and forskolin-stimulated elevation of PRL mRNA. The calcium agonist barium (1 mM) produced a 2-fold increase in both beta-endorphin and PRL release, which was blocked by D600. Treatment of cells with barium had no effect on POMC mRNA levels, but increased PRL mRNA levels. D600 treatment of cells partially blocked barium-stimulated PRL mRNA levels. These findings demonstrate a calcium-dependent as well as a calcium-independent component of CRF-stimulated beta-endorphin secretion and CRF-stimulated POMC mRNA elevation. In contrast, PRL secretion and biosynthesis appear to be totally calcium-dependent processes.
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D005711:Gallopamil / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D010903:Pituitary Gland, Anterior / Q000502:physiology*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D012333:RNA, Messenger; D005576:Colforsin; D001464:Barium; D005711:Gallopamil; D011333:Pro-Opiomelanocortin; D011388:Prolactin; D003346:Corticotropin-Releasing Hormone; D002118:Calcium