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Exp Clin Endocrinol. 1990 Sep;96(1):15-24.

Effects of prolonged administration of lovastatin, an inhibitor of cholesterol synthesis, on the morphology and function of rat Leydig cells.

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Department of Anatomy, University of Padua, Italy.


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.

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