Exogenous Arachidonate Restores the Dimethoate‐Induced Inhibition of Steroidogenesis in Rat Interstitial Cells

Abstract

The present work studies the potential restorative effect of polyunsaturated fatty acids (PUFA, 5 μM/24 h) on the dimethoate (DMT)‐induced inhibition of testosterone biosynthesis in Leydig cells isolated from rat testes. Various fatty acids (FA) from the n‐6 (18:2, 20:3, 20:4, 22:4 and 22:5) and n‐3 (18.3, 20:5, 22:5, 22:6) series were assayed in Leydig cells, alone (as delipidated BSA complexes) and in combination with DMT (1 ppm). The n‐6 FA stimulated lipid peroxidation (LPO) and inhibited the activities of steroidogenic enzymes (3β‐ and 17β‐hydroxysteroid dehydrogenases). The n‐3 FA exerted an anti‐oxidant effect, decreasing the production of thiobarbituric‐acid reactive substances (TBARS) and inhibiting phospholipase A2 activity. The biosynthesis of testosterone in DMT‐treated cultures was completely normalized by ARA (20:4n‐6) and partially restored by the addition of 20:3n‐6, increasing ARA content inside the mitochondria. The other FA assayed failed to restore androgenesis. COX‐2 protein and prostaglandin F2α and E2 production were stimulated by 20:3n‐6, ARA, 18:3n‐3 and 20:5 n‐3. COX‐2 protein decreased upon addition of 22:5n‐3 and 22:6n‐3. StAR protein was increased by ARA and partially increased by 20:3n‐6, likely due to its metabolic conversion into ARA. Both FA increased the mitochondrial cholesterol pool available for testosterone biosynthesis. The rate of androgenesis is likely the result of various regulatory factors acting concomitantly on the physiology of Leydig cells.

Influence of Dietary Long-Chain Polyunsaturated Fatty Acids and ω6 to ω3 Ratios on Head Kidney Lipid Composition and Expression of Fatty Acid and Eicosanoid Metabolism Genes in Atlantic Salmon (Salmo salar)

“…This finding supports previous human macrophage studies which indicated that SFA induced cox2 expression (Lee et al, 2001;Rocha et al, 2016). Astiz et al (2012) showed that addition of 22:4ω6 and 22:5ω6 did not impact the production of COX2 in rat testis cells. However, a previous study on mouse brain indicated that reduction in the levels of ARA metabolites 22:4ω6 and 22:5ω6 reflected a shift of ARA from LC-PUFA biosynthesis prostaglandin or leukotriene synthesis (McNamara et al, 2009).…”

Pesticide-induced decrease in rat testicular steroidogenesis is differentially prevented by lipoate and tocopherol

“…In a previous work from our laboratory, we demonstrated that D displays a complex mechanism of action involving disturbance of testosterone production reducing both, the plasma and interstitial Leydig cell concentrations, damage to the antioxidant defense system, decrease araquidonate content in phospholipids, inhibit StAR protein expression with simultaneous stimulation of COX-2 (overproduction of PGF2a) and inhibition of the steroidogenic enzymes 17bHSD and 3bHSD (Astiz et al, 2009a). Damage caused to the steroidogenic status of Leydig cells exposed to D could be reverted by exogenous arachidonate (Astiz et al, 2012). Moreover, recent studies in rats suggested that exposure to G during the pre-and post-natal periods induced adverse effects on male reproductive performance (Dallegrave et al, 2007).…”

Steroidogenesis in Leydig cells: effects of aging and environmental factors

“…Dimethoate, a widely used organophosphate, was reported to reduce Leydig cell steroidogenic function in association with decreased arachidonate and increased COX-2 (Astiz et al . 2009, Astiz et al . 2012).…”