Secondary alcohol dehydrogenase as a marker of the conversion between progestagens and androgens in the rat testis.
Supraphysiological doses of LHRH-Analogue blocked the C21 to C19 steroid conversion in the mature Wistar rats testis. It was associated with inhibition of the NAD-dependent secondary alcohol-dehydrogenase (A-D II) histochemical reaction in the Leydig cells. Under this condition the treated group exhibited lower testis, seminal vesicle and prostate weights, intratesticular (IT) and plasmatic (PL) increased progesterone (P4) and decreased testosterone (T) concentrations. We also observed a decrease in the IT androstenedione (delta 4) concentration without pregnenolone (P5) change. All these data confirm a chemical castration pointing to a blockade at the level of the P450C21scc (17 alpha-hydroxylase/17-20 desmolase) enzyme complex. After hCG administration there is no difference in sexual gland weights, while steroid's biosynthesis are stimulated and all IT and PL steroid concentrations increase. A-D II showed a lower optical density in the LHRH-A treated groups and no differences in the hCG rats. The hydroxylase or lyase activity of the P450C21scc may change under certain hormonal conditions as occurs in adrenarche, probably due to conformational changes in the active site of the enzyme system since it is encoded by only one gene. We suppose that the secondary alcohol itself and not the coenzyme reacts with the enzyme active site inhibited by the LHRH-A, since the NAD dependent 3 beta, hydroxysteroid-dehydrogenase (3 beta HOST-D) is affected in the opposite sense. This study shows A-D II reaction as a marker of the mediated P450C21scc enzyme complex activity in the rat testis Leydig cells.
de Oliveira
J A
JA
Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Campos
L M
LM
Scandar
M P
MP
Rosa e Silva
A A
AA
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000031:analogs & derivatives; D008297:Male; D009243:NAD / Q000378:metabolism; D011372:Progestins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
D000728:Androgens; D015415:Biomarkers; D006063:Chorionic Gonadotropin; D011372:Progestins; D009243:NAD; D007987:Gonadotropin-Releasing Hormone; D003577:Cytochrome P-450 Enzyme System; D015096:3-Hydroxysteroid Dehydrogenases; D000426:Alcohol Dehydrogenase