OxeR1 regulates angiotensin II and cAMP-stimulated steroid production in H295R human adrenocortical cells

DATTILO, M.; NEUMAN, I.; MALOBERTI, P.; CORNEJO MACIEL, F.

Chicago, IL

Congreso; XXIst Adrenal Cortex Conference.; 2014

Adrenal Cortex Conference

Hormonal regulation of steroidogenesis involves the participation of arachidonic acid, precursor of the lipoxygenated products needed for the induction of StAR protein. In other systems, it is postulated that the secreted lipoxigenated products would function in an autocrine manner to stimulate a membrane receptor called OxeR1, with high affinity for 5-lipoxygenase products. Previously we showed the presence of this receptor in mineralocorticoid producing human H295R cell line. By means of pharmacological tools, we demonstrated that the OxeR1 is involved, at least in part, in the action of cAMP. This study continues with the identification of the OxeR1 as mediator of the hormonal response. For this purpose, the cDNA of the OxeR1 obtained from human H295R adrenocortical cells was cloned into an expression vector. As expected, transfection of H295R cells with this construct increased the OxeR1 protein signal compared with the endogenous expression at the expected molecular weight of 50 kDa. The response to stimulation with 8Br-cAMP and angiotensin II was determined in H295R cells overexpressing OxeR1, recording a significant increase in steroid production and StAR protein expression. In conclusion, the membrane receptor OxeR1 is involved in the induction of StAR protein and activation of steroidogenesis triggered by cAMP or Angiotensin II.