Effect of chronic treatment with new benzylidene-thiazolidine-2,4-dione (LPSF/GQ-06) with potential hypoglycemic on rat Leydig cell steroidogenesis

Thiazolidinediones work by sensitizing the action of insulin by acting as ligands for the PPAR receptor. This study describes the effects of chronic treatment with new benzylidene-thiazolidine-2,4-dione (LPSF/GQ-06) on Leydig cell steroidogenic capacity, and expression of the steroidogenic acute regulatory protein (StAR) and cholesterol side-chain cleavage enzyme (P450scc) in normal rats. Twelve adult male Wistar rats were treated with LPSF/GQ-06 (5 mg/kg) administered by gavage for 15 days. Testosterone in plasma and incubation medium was measured by radioimmunoassay. The StAR and P450scc expression was detected by immunocytochemistry. The levels of total circulating testosterone were increased by LPSF/GQ-06 treatment. The ability of LPSF/GQ-06 to affect the production of testosterone by Leydig cells was examined using an ex vivo model. The production of testosterone was induced by activators of the cAMP/PKA pathway (hCG and dbcAMP) or substrates of steroidogenesis (22(R)-hydroxycholesterol, substrate for the P450scc enzyme, and pregnenolone, the product of the P450scc-catalyzed step). An increase in basal or induced testosterone production was observed in Leydig cells from LPSF/GQ-06-treated rats. The ultrastructural and immunocytochemical analysis showed that LPSF/GQ-06-treated Leydig cells presented morphological characteristics similar to those of control cells as well as similar labeling to StAR and P450scc throughout the cytoplasm of control and treated cells. We can therefore conclude that the stimulatory action of the LPSF/GQ-06 on testosterone production is not due to an increase of the quantity of StAR or P450scc. These results suggest that the activity of these two proteins as well as of other steroidogenic enzymes is augmented by LPSF/GQ-06.