The broad health relatedness of this proposal is to understand more regarding the role of aldosterone in basal steroidogenesis. Cadmium will be used as an inhibitor of aldosterone production in H295R human adrenal cortical cells.
The specific aims of the project are as follows: 1.) To demonstrate that basal steroid synthesis by H295R cells is affected by cadmium in a manner similar to that observed for cadmium-treated Y-1 adrenal cells. 2.) To determine the extent of competition between calcium and cadmium at sites affected by cadmium during basal steroidogenesis. 3.) To identify the steroid synthesis-dependent intracellular and mitochondrial sites affected by calcium and cadmium ions in unstimulated H295R human adrenal tumor cells by examining cadmium competition with calcium during cholesterol transfer to the inner mitochondrial membrane. The results obtained in this proposal will contribute to the body of knowledge regarding calcium's role in steroidogenesis by elucidating mechanisms within human adrenal cortical cells that lead to steroidogenesis.