Rat Leydig cells use apolipoprotein E depleted high density lipoprotein toregulate testosterone production

Rat HDL are known to increase testosterone production by cultured Leydig ce lls either following gonadotropin stimulation or cholesteryl ester depletio n. However, rat HDL contain apolipoprotein E and have a high affinity for t he members of the low density receptor family such as LDL receptor, LDL rec eptor related protein and VLDL receptor. In contrast with the adrenal cells , the contribution of apo A-I and apo E pathways in HDL cholesterol uptake has not been yet evidenced in rat Leydig cells. Recent data provided eviden ce that hCG stimulates scavenger receptor BI expression in testes. In order to investigate if testosterone production can be stimulated by apo E deple ted HDL, we compared the level of testosterone stimulation by HDL with or w ithout apo E first, in presence of saturating dose of hCG (1 IU/ml) and sec ond, after depletion of cholesterol synthesis by pravastatin, an inhibitor of HMG-CoA reductase. In presence of hCG, HDL with or without apo E increas ed testosterone production respectively by 37 and 25%. Pravastatin at 100 m ug/ml inhibited the cholesterol synthesis and the testosterone production b y 25% and decreased the cholesteryl content by 25%. The addition of HDL wit h or without apo E (50 mug protein HDL/ml) completely overcame the depletio n of cellular cholesteryl esters and the inhibition of testosterone product ion induced by pravastatin. In the presence of heparin, apo E depleted HDL overcame the testosterone production induced by pravastatin, indicating tha t uptake of HDL without apo E via a secretion of apo E by the cells themsel ves was not involved. Therefore, in absence of apo E, it is suggested that rat Leydig cells used HDL to regulate steroidogenesis via an apolipoprotein A-I pathway.