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

• Published in: Lipids 2012-06, Vol.47 (6), p.557-569
• Main Authors: Astiz, Mariana, Hurtado de Catalfo, Graciela, J. T. de Alaniz, María, Marra, Carlos Alberto
• Format: Article
• Language: English
• Subjects: 17-Hydroxysteroid Dehydrogenases - antagonists & inhibitors; 17-Hydroxysteroid Dehydrogenases - metabolism; 3-Hydroxysteroid Dehydrogenases - antagonists & inhibitors; 3-Hydroxysteroid Dehydrogenases - metabolism; Androgenesis; Animals; Antioxidants - pharmacology; Arachidonic acid; Arachidonic Acid - pharmacology; Biomedical and Life Sciences; Biosynthesis; Cell Survival - drug effects; Cells, Cultured; Cholesterol; Cholinesterase Inhibitors - pharmacology; COX‐2; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Dimethoate; Dimethoate - pharmacology; Fatty Acids - pharmacology; Gene Expression; Leydig Cells - drug effects; Leydig Cells - enzymology; Leydig Cells - metabolism; Life Sciences; Lipid Peroxidation; Lipidology; Male; Medical Biochemistry; Medicinal Chemistry; Microbial Genetics and Genomics; Mitochondria - metabolism; Neurochemistry; Nutrition; Original Article; Oxidative stress; Oxidizing agents; Peroxidation; Phospholipase A2 Inhibitors; Phospholipases A2 - metabolism; Phosphoproteins - genetics; Phosphoproteins - metabolism; Polyunsaturated fatty acids; Prostaglandins; Prostaglandins - metabolism; PUFA; Rat interstitial cells; Rats; Rats, Wistar; StAR; Testosterone - biosynthesis; Thiobarbituric Acid Reactive Substances - metabolism
• ISSN: 0024-4201; 1558-9307
• DOI: 10.1007/s11745-012-3669-y

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 A 2 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.