Site of gossypol inhibition of steroidogenesis in purified mouse Leydig cells.
Gossypol, a phenolic compound that has been studied as a potential male contraceptive, inhibits basal and LH-stimulated testosterone release from Leydig cells in vitro. The present study investigates the mechanism of this inhibition using preparations of purified mouse Leydig cells. Gossypol inhibited LH-stimulated progesterone, 17-hydroxyprogesterone and androstenedione production by mouse Leydig cells incubated in vitro. It also inhibited dibutyryl cyclic AMP-stimulated production of testosterone but was without effect in the presence of added pregnenolone or 25-hydroxycholesterol. These results suggest gossypol exerts its major inhibitory effect on Leydig cell function at a point between LH-dependent stimulation of cyclic AMP dependent protein kinase activity and increased availability of cholesterol for side chain cleavage.
D019326:17-alpha-Hydroxyprogesterone; D000735:Androstenedione / Q000096:biosynthesis; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D006072:Gossypol / Q000494:pharmacology*; D006888:Hydroxycholesterols / Q000494:pharmacology; D006908:Hydroxyprogesterones / Q000096:biosynthesis; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000494:pharmacology; D008297:Male; D051379:Mice; D011284:Pregnenolone / Q000494:pharmacology; D011374:Progesterone / Q000096:biosynthesis*; D013739:Testosterone / Q000096:biosynthesis*
D006888:Hydroxycholesterols; D006908:Hydroxyprogesterones; D013739:Testosterone; D000735:Androstenedione; D011374:Progesterone; D003994:Bucladesine; D019326:17-alpha-Hydroxyprogesterone; D011284:Pregnenolone; C007997:25-hydroxycholesterol; D007986:Luteinizing Hormone; D006072:Gossypol