Integration of new regulatory strategies into the network of an endocrine control system: limitation of androgen secretion by rat testis is achieved by substrate-dependent modulation of P450XVII enzyme concentration and catalytic efficiency.
In addition to the well-known control circuits involved in the regulation and adaptation of testicular androgen biosynthesis, it is proposed that two new control strategies are involved in the maintenance of steady-state testosterone secretion rates by testicular Leydig cells. Cytochrome P450XVII (steroid-17 alpha-monooxygenase/steroid-17,20-lyase), one key enzyme in steroid hormone biosynthesis, responds to external human choriogonadotropin stimulation with an oxygen-dependent and substrate flux-dependent inactivation and decomposition, and increased substrate availability decreases the efficiency of androgen formation in favour of abortive intermediate leakage. These results are discussed as a paradigm of substrate-dependent modulation of cytochrome P450 activities.
Kühn-Velten
W N
WN
Department of Gynecology and Obstetrics, Heinrich-Heine-Universität, Düsseldorf, Germany.
D000446:Aldehyde-Lyases / Q000378:metabolism*; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005246:Feedback; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008954:Models, Biological; D051381:Rats; D013254:Steroid 17-alpha-Hydroxylase; D013737:Testis / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013739:Testosterone / Q000378:metabolism*
D000728:Androgens; D006063:Chorionic Gonadotropin; D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System; D013254:Steroid 17-alpha-Hydroxylase; D000446:Aldehyde-Lyases