title: 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 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.
authors.affiliation: INIBIOLP (Instituto de Investigaciones Bioquímicas de La Plata), CCT La Plata, CONICET-UNLP, Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Calles 60 y 120, 1900 La Plata, Argentina.
authors.forename: Mariana
authors.initials: M
authors.lastname: Astiz
authors.forename: Graciela
authors.initials: G
authors.lastname: Hurtado de Catalfo
authors.forename: María J T
authors.initials: MJ
authors.lastname: de Alaniz
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Marra
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004117:Dimethoate / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology; D015870:Gene Expression; D007985:Leydig Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D015227:Lipid Peroxidation; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000096:biosynthesis*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D005227:Fatty Acids; D064801:Phospholipase A2 Inhibitors; D010750:Phosphoproteins; D011453:Prostaglandins; D017392:Thiobarbituric Acid Reactive Substances; D000098682:Steroidogenic Acute Regulatory Protein; D016718:Arachidonic Acid; D013739:Testosterone; D002784:Cholesterol; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D054467:Phospholipases A2; D004117:Dimethoate