Rofecoxib prevents dimethoate-induced inhibition of testosterone biosynthesis in rat Leydig cells

ASTIZ MARIANA; HURTADO DE CATALFO GRACIELA; TACCONI DE ALANIZ MARÍA J.; MARRA CARLOS ALBERTO

San Miguel de Tucumán, Tucumán, Argentina

Congreso; XLV Reunión Anual de SAIB (Sociedad Argentina de Investigación Bioquímica y Biología Molecular); 2009

SAIB (Sociedad Argentina de Investigación en Bioquímica y Biología Molecular)

Previous work from our lab demonstrated that administration of dimethoate (D) to rats increased COX-2 expression, decreased transcription and translation of StAR protein, and increased the level of PGE2 and PGF2alpha. Concomitantly, plasma LH and FSH was increased while testosterone was diminished compared to control. These alterations were paralleled by an oxidative stress condition (OS) induced by D. In order to study the contribution of prostaglandin level and the OS in the mechanism(s) involved in testosterone biosynthesis inhibition, we treated rats simultaneously with D and either alpha-tocoferyldiacetate (T) or rofecoxib (R) at doses that neutralized lipid peroxidation and COX-2 activity, respectively. T injection reduced OS; however, hormonal changes induced by D persisted. The decreased level of arachidonate (A) observed under D treatment was not normalized by T association. In contrast, injection of R raised the level of A, decreased PGF2alpha production, and normalized hormonal level although the production of lipoperoxides still persisted elevated. When D, T and R were administered in combination all the parameters returned to control values. The main conclusion was that there was a compensation of the opposite effects caused by D and R, being the contribution of prostaglandin biosynthesis the main target of the alteration evoked by D on the androgenic status.