14 research outputs found
Molecular Mechanism of Steroidogenic Factor 1 (SF1) Mediated Repression of CYP11B2 Expression.
Effect of KCNJ5 Mutations on Gene Expression in Aldosterone-Producing Adenomas and Adrenocortical Cells.
Outcome of Clinical Genetic Testing in Patients with Features Suggestive for Hereditary Predisposition to PTH-Mediated Hypercalcemia
Steroid metabolism gene variants and their genotype-phenotype correlations in Chinese early-onset hypertension patients
Molecular and Electrophysiological Analyses of ATP2B4 Gene Variants in Bilateral Adrenal Hyperaldosteronism
Mitochondrial cAMP and Ca(2+) metabolism in adrenocortical cells.
The biological effects of physiological stimuli of adrenocortical glomerulosa cells are predominantly mediated by the Ca(2+) and the cAMP signal transduction pathways. The complex interplay between these signalling systems fine-tunes aldosterone secretion. In addition to the well-known cytosolic interactions, a novel intramitochondrial Ca(2+)-cAMP interplay has been recently recognised. The cytosolic Ca(2+) signal is rapidly transferred into the mitochondrial matrix where it activates Ca(2+)-sensitive dehydrogenases, thus enhancing the formation of NADPH, a cofactor of steroid synthesis. Quite a few cell types, including H295R adrenocortical cells, express the soluble adenylyl cyclase within the mitochondria and the elevation of mitochondrial [Ca(2+)] activates the enzyme, thus resulting in the Ca(2+)-dependent formation of cAMP within the mitochondrial matrix. On the other hand, mitochondrial cAMP (mt-cAMP) potentiates the transfer of cytosolic Ca(2+) into the mitochondrial matrix. This cAMP-mediated positive feedback control of mitochondrial Ca(2+) uptake may facilitate the rapid hormonal response to emergency situations since knockdown of soluble adenylyl cyclase attenuates aldosterone production whereas overexpression of the enzyme facilitates steroidogenesis in vitro. Moreover, the mitochondrial Ca(2+)-mt-cAMP-Ca(2+) uptake feedback loop is not a unique feature of adrenocortical cells; a similar signalling system has been described in HeLa cells as well