Seasonal changes in the activity of cytochrome P450c17 from the testis of Bufo arenarum.

FERNANDEZ SOLARI JJ; POZZI AG; CEBALLOS N

JOURNAL OF COMPARATIVE PHYSIOLOGY B-BIOCHEMICAL SYSTEMIC AND ENVIRONMENTAL PHYSIOLOGY

Springer Verlag

Lugar: Berlin; Año: 2002 vol. 172 p. 685 - 690

0174-1578

In Bufo arenarum, the biosynthesis of testosterone and 5a-dihydrotestosterone takes place through a complete 5-ene pathway, 5-androsten-3b,17b-diol being the immediate precursor of testosterone. Besides androgens, testes are able to synthesise 5a-pregnan-3,20-dione and several 3a and 20a reduced derivatives. During the breeding season, steroid biosynthesis turns from androgen to C21-steroid production. As a consequence, the cytochrome P450 17-hydroxylase, C17,20-lyase (CypP450c17) could be a key enzyme in that metabolic shift. The present study demonstrates that in testes of B. arenarum, CypP450c17 co-localises with glucose-6-phosphatase in the microsomal fraction. CypP450c17 possesses more affinity for pregnenolone than for progesterone in both non-reproductive (Km=43.76}4.63 nM and 2,170}630 nM, respectively) and reproductive (Km= 37.46} 4.19 nM and 3,060}190 nM, respectively) seasons. These results could explain the predominance of the 5-ene pathway for testosterone biosynthesis. Toad CypP450c17 activity is higher in the non-reproductive period than the reproductive period, suggesting that this enzyme is an important factor in toad steroidogenic changes. Animals in reproductive conditions showed a significant reduction in circulating androgens. This is in agreement with the decrease in Vmax of cytochrome P450 17-hydroxylase activity, enhancing the physiological relevance of these in vitro results Bufo arenarum, the biosynthesis of testosterone and 5a-dihydrotestosterone takes place through a complete 5-ene pathway, 5-androsten-3b,17b-diol being the immediate precursor of testosterone. Besides androgens, testes are able to synthesise 5a-pregnan-3,20-dione and several 3a and 20a reduced derivatives. During the breeding season, steroid biosynthesis turns from androgen to C21-steroid production. As a consequence, the cytochrome P450 17-hydroxylase, C17,20-lyase (CypP450c17) could be a key enzyme in that metabolic shift. The present study demonstrates that in testes of B. arenarum, CypP450c17 co-localises with glucose-6-phosphatase in the microsomal fraction. CypP450c17 possesses more affinity for pregnenolone than for progesterone in both non-reproductive (Km=43.76}4.63 nM and 2,170}630 nM, respectively) and reproductive (Km= 37.46} 4.19 nM and 3,060}190 nM, respectively) seasons. These results could explain the predominance of the 5-ene pathway for testosterone biosynthesis. Toad CypP450c17 activity is higher in the non-reproductive period than the reproductive period, suggesting that this enzyme is an important factor in toad steroidogenic changes. Animals in reproductive conditions showed a significant reduction in circulating androgens. This is in agreement with the decrease in Vmax of cytochrome P450 17-hydroxylase activity, enhancing the physiological relevance of these in vitro results