Wanderley M I, Udrisar D P
Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, Brazil.
Acta Physiol Pharmacol Ther Latinoam. 1994;44(4):135-41.
Ethanol and acetaldehyde have been shown to inhibit testicular steroidogenesis. However the mechanism(s) of signal transduction involved in their action is still unclear. We examined the possible involvement of phospholipid-sensitive, calcium-dependent protein kinase (protein Kinase C, PK-C) in the intracellular mechanism of action of ethanol and acetaldehyde by stimulating testosterone production in rat testicular interstitial cells with LHRH and the phorbol ester PDBu, both of which activate PK-C at receptor (LHRH) and post-receptor (PDBu) sites. Ethanol (2000 mg %) inhibited 10(-7) M LHRH and 200 nM PDBu-stimulated testosterone production by 81 +/- 4.7% and 60 +/- 20.4%, respectively. Acetaldehyde (20 mg %) reduced the amount of testosterone produced by 10(-7) M LHRH and 200 nM PDBu by 59.4 +/- 1.2% and 52.5 +/- 5.4% respectively. Basal testosterone levels were unaffected by ethanol and reduced by acetaldehyde. However, the functional test of cell viability by preincubating cells with these doses of ethanol and acetaldehyde did not decrease their ability to respond appropriately to subsequent stimulation with LHRH, demonstrating that cell viability was unaffected by incubation with these drugs. The data presented here suggest that direct ethanol and acetaldehyde exposure results in a reduced ability of the testicular interstitial cells to respond to stimulation of PK-C pathway.
乙醇和乙醛已被证明可抑制睾丸类固醇生成。然而，其作用所涉及的信号转导机制仍不清楚。我们通过用促黄体生成素释放激素（LHRH）和佛波酯PDBu刺激大鼠睾丸间质细胞中的睾酮生成，来研究磷脂敏感的钙依赖性蛋白激酶（蛋白激酶C，PK - C）是否可能参与乙醇和乙醛的细胞内作用机制，这两种物质均可在受体（LHRH）和受体后（PDBu）位点激活PK - C。乙醇（2000mg%）分别抑制10(-7)M LHRH和200nM PDBu刺激的睾酮生成达81±4.7%和60±20.4%。乙醛（20mg%）分别使10(-7)M LHRH和200nM PDBu产生的睾酮量减少59.4±1.2%和52.5±5.4%。基础睾酮水平不受乙醇影响，但受乙醛降低。然而，用这些剂量的乙醇和乙醛预孵育细胞进行细胞活力功能测试，并未降低它们对随后LHRH刺激的适当反应能力，表明细胞活力不受与这些药物孵育的影响。此处呈现的数据表明，直接暴露于乙醇和乙醛会导致睾丸间质细胞对PK - C途径刺激的反应能力降低。
