REGULATION OF THE CHOLESTEROL ESTER CYCLE AND PROGESTERONE SYNTHESIS BY JUVENILE-HORMONE IN MA-10 LEYDIG TUMOR-CELLS

We had previously reported that juvenile hormone III (JH III) and the JH analogue 2-(4-phenoxy phenoxy)-ethoxytetrahydropyran exert inhibito ry effects on progesterone synthesis by blocking cAMP production in hC G-stimulated MA-10 Leydig tumor cells. In the present study, the effec ts of JH analogue upon the biosynthetic pathway of progesterone synthe sis have been examined. Our results demonstrated that JH analogue inhi bited progesterone production even in the presence of 20-hydroxycholes terol or 25-hydroxycholesterol. Furthermore, although JH analogue inhi bited pregnenolone production in hCG-stimulated MA-10 cells the activi ty of the 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) was unaffec ted. These data suggest that JH analogue might inhibit the steroidogen ic pathway in Leydig tumor cells by inhibiting the activity of the cho lesterol side chain cleavage (CSCC) enzymatic complex. The JH analogue was also evaluated for inhibitory actions on cholesterol availability . An important effect of this compound was the interference with the c ellular process of plasma membrane cholesterol internalization. Moreov er, JH analogue inhibited not only the use of cholesterol ester for st eroid biosynthesis under Bt2cAMP stimulation, but also the cholesterol ester hydrolase (CEH) activity in MA-10 Leydig tumor cells.