Steroidogenic action of calcium ions in isolated adrenocortical cells

Abstract

The corticotropin-induced increase of total intracellular and receptor-bound cyclic AMP in isolated rat adrenocortical cells was strictly dependent on extracellular Ca2+. A rise in bound cyclic AMP with rising Ca2+ concentrations was accompanied by a decrease in free cyclic AMP-receptor sites. A Ca2+-transport inhibitor abolished the rise in bound cyclic AMP induced by corticotropin. These data suggested that during stimulation by corticotropin some Ca2+ 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 Ca2+ concentration in the presence of corticotropin and GTP. When cells were treated under specific conditions, corticosterone production could be activated by Ca2+ in the absence of corticotropin (cells primed for Ca2+). Ca2+-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 Ca2+ were not able, however, to increase the cyclic AMP pools in non-primed cells, unlike corticotropin in nonprimed cells or Ca2+ in cells primed for Ca2+. It was concluded that during stimulation by either corticotropin or Ca2+ a possible cellular uptake of Ca2+ must be very limited and directed to a specific site which may affect the coupling of the hormone-receptor–adenylate cyclase complex.