Andreis P G, Cavallini L, Mazzocchi G, Nussdorfer G G
Department of Anatomy, University of Padua, Italy.
Exp Clin Endocrinol. 1990 Sep;96(1):15-24. doi: 10.1055/s-0029-1210983.
We examined the effects of a prolonged treatment with lovastatin, a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on the morphology and function of rat Leydig cells. Twenty-four h after the first lovastatin injection, no conspicuous ultrastructural changes were found, but isolated Leydig cells showed a notable reduction in their basal and HCG-stimulated testosterone production. By prolonging lovastatin administration (daily injections for 3 and 5 days), Leydig cells progressively recovered their secretory activity, and this was associated with a striking proliferation of smooth endoplasmic reticulum and peroxisomes. The hypothesis is discussed that these morphologic changes are the counterpart of an enhanced newly synthesis of HMG-CoA reductase, that is the expression of a compensatory response of Leydig cells aimed at maintaining an adequate production of cholesterol (i.e. testosterone precursors) in spite of the chronic competitive inhibition of HMG-CoA reductase by lovastatin.
我们研究了用洛伐他汀（一种强效的3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶竞争性抑制剂）进行长期治疗对大鼠睾丸间质细胞形态和功能的影响。首次注射洛伐他汀24小时后，未发现明显的超微结构变化，但分离出的睾丸间质细胞显示其基础睾酮分泌及人绒毛膜促性腺激素（HCG）刺激的睾酮分泌显著减少。通过延长洛伐他汀给药时间（每日注射3天和5天），睾丸间质细胞逐渐恢复其分泌活性，这与滑面内质网和过氧化物酶体的显著增殖有关。本文讨论了这样一种假说，即这些形态学变化是HMG-CoA还原酶新合成增加的对应表现，也就是说，尽管洛伐他汀对HMG-CoA还原酶有慢性竞争性抑制作用，但睾丸间质细胞的这种变化是一种旨在维持足够胆固醇（即睾酮前体）生成的代偿性反应的表达。
