Astiz Mariana, Hurtado de Catalfo Graciela, de Alaniz María J T, Marra Carlos Alberto
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.
Lipids. 2012 Jun;47(6):557-69. doi: 10.1007/s11745-012-3669-y. Epub 2012 Apr 3.
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.
本研究探讨了多不饱和脂肪酸（PUFA，5 μM/24 h）对乐果（DMT）诱导的大鼠睾丸间质细胞睾酮生物合成抑制的潜在恢复作用。在间质细胞中检测了来自n-6系列（18:2、20:3、20:4、22:4和22:5）和n-3系列（18:3、20:5、22:5、22:6）的各种脂肪酸（FA），单独检测（作为脱脂牛血清白蛋白复合物）以及与DMT（1 ppm）联合检测。n-6脂肪酸刺激脂质过氧化（LPO）并抑制类固醇生成酶（3β-和17β-羟基类固醇脱氢酶）的活性。n-3脂肪酸发挥抗氧化作用，降低硫代巴比妥酸反应性物质（TBARS）的产生并抑制磷脂酶A2活性。在DMT处理的培养物中，睾酮的生物合成通过花生四烯酸（ARA，20:4n-6）完全恢复正常，并通过添加20:3n-6部分恢复，增加了线粒体内的ARA含量。检测的其他脂肪酸未能恢复雄激素生成。COX-2蛋白以及前列腺素F2α和E2的产生受到20:3n-6、ARA、18:3n-3和20:5 n-3的刺激。添加22:5n-3和22:6n-3后COX-2蛋白减少。ARA增加了类固醇生成急性调节蛋白（StAR）的含量，20:3n-6使其部分增加，这可能是由于其代谢转化为ARA所致。两种脂肪酸都增加了可用于睾酮生物合成的线粒体胆固醇池。雄激素生成速率可能是多种调节因子同时作用于间质细胞生理学的结果。
