OxeR1, a leukotriene receptor, is present and active in steroidogenic cells

COOKE, M.; CORNEJO MACIEL, F.

Mendoza, Mendoza

Congreso; XLVIII Reunión Anual Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2012

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

Hormonal regulation of steroidogenesis involves arachidonic acid (AA) metabolization through 5-lipoxygenase (5-LOX) pathway. The products, especially 5-HpETE, are involved in the activation of the steroidogenic acute regulatory (StAR) protein promoter. However, the mechanism of action of these compounds is still unknown. Besides, the oxoeicosanoid receptor OXER1 is a GPCR membrane receptor of the leukotriene family, with high affinity and response to 5-lipoxygenase AA derivatives. Thus, we tested the presence and functionality of the OXER1 in steroidogenic cells. RT-PCR and western blot analysis demonstrated the presence of the mRNA and protein of the receptor in the human H295R adrenocortical cells. The treatment of MA-10 cells, murine Leydig cell line, with 8Br-cAMP together with docosahexaenoic acid (an antagonist of the receptor) partially reduced StAR induction and steroidogenesis. 5-oxo-ETE -the agonist with higher affinity and potency on the receptor- increased cAMP-dependent steroid production in a dose-dependent fashion. This agonist also increased StAR mRNA and protein levels in both cell lines. These results lead us to conclude that AA might modulate StAR induction and steroidogenesis through the autocrine or paracrine action of 5-LOX products on the membrane receptor OXER1.