Steroidogenic action of calcium ions in isolated adrenocortical cells.
The corticotropin-induced increase of total intracellular and receptor-bound cyclic AMP in isolated rat adrenocortical cells was strictly dependent on extracellular Ca(2+). A rise in bound cyclic AMP with rising Ca(2+) concentrations was accompanied by a decrease in free cyclic AMP-receptor sites. A Ca(2+)-transport inhibitor abolished the rise in bound cyclic AMP induced by corticotropin. These data suggested that during stimulation by corticotropin some Ca(2+) has to be taken up in order to promote the rise of the relevant cyclic AMP pool. In agreement with this view, adenylate cyclase activity from isolated cells proved also to be dependent on a sub-millimolar Ca(2+) concentration in the presence of corticotropin and GTP. When cells were treated under specific conditions, corticosterone production could be activated by Ca(2+) in the absence of corticotropin (cells primed for Ca(2+)). Ca(2+)-induced steroidogenesis of these cells, in the absence of corticotropin, was also accompanied by an increase in total intracellular and receptor-bound cyclic AMP, as was found previously with corticotropin-induced steroidogenesis in non-primed cells. Calcium ionophores increasing the cell uptake of Ca(2+) were not able, however, to increase the cyclic AMP pools in non-primed cells, unlike corticotropin in nonprimed cells or Ca(2+) in cells primed for Ca(2+). It was concluded that during stimulation by either corticotropin or Ca(2+) a possible cellular uptake of Ca(2+) must be very limited and directed to a specific site which may affect the coupling of the hormone-receptor-adenylate cyclase complex.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D003345:Corticosterone / Q000096:biosynthesis*; D000242:Cyclic AMP / Q000378:metabolism; D066298:In Vitro Techniques; D051381:Rats; D011953:Receptors, Cyclic AMP / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D011953:Receptors, Cyclic AMP; D000324:Adrenocorticotropic Hormone; D014700:Verapamil; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium; D003345:Corticosterone