Analysis of the expression and function of OxeR1, an eicosanoid receptor, in steroidogenic cells

DI CONSOLI, H.; COOKE, M.; CORNEJO MACIEL, F.

League City, Texas

Conferencia; XXth Adrenal Cortex Conference; 2012

Adrenal Cortex Conference

Hormonal regulation of steroidogenesis involves arachidonic acid (AA) release and metabolization through 5-lipoxygenase pathway. One of the products of this pathway, 5-hidroperoxyeicosatetraenoic acid (5-HpETE), acts as a modulator of the activity of the steroidogenic acute regulatory (StAR) protein promoter. Besides, the OxeR1 is a membrane protein with high affinity and response to 5-HpETE, among other AA derivatives. The aim of our work was to elucidate whether this receptor may be involved in steroidogenesis. RT-PCR demonstrated the presence of the mRNA of the receptor in the human H295R adrenocortical cells. The treatment of H295R or MA-10 cells (murine Leydig cell line) with 8Br-cAMP together with docosahexaenoic acid (DHA, an antagonist of the receptor) partially reduced steroid production. This partial inhibition is due to the fact that AA per se or other of its metabolites would exert OxeR1-independent effects. Similarly, DHA decreased 8Br-cAMP-stimulated StAR promoter activity and mRNA and protein levels. These results lead us to conclude that AA might modulate StAR promoter activity and steroidogenesis partially through 5- HpETE production and activation of a membrane receptor, such as OxeR1.