Citation

Kossor DC, Kominami S, Takemori S, Colby HD. J. Steroid Biochem. Mol. Biol. 1992; 42(3-4): 421-424.

Copyright

(Copyright © 1992, Elsevier Publishing)

DOI

10.1016/0960-0760(92)90147-b

PMID

1606053

Abstract

Studies were done to determine the role of the 17 alpha-hydroxylase in the conversion of 7 alpha-thiospironolactone (7 alpha-thio-SL) to a reactive metabolite causing the degradation of testicular cytochrome P-450. Incubation of guinea pig testicular microsomes with 7 alpha-thio-SL plus NADPH resulted in an approx. 70% decline in cytochrome P-450 content and even greater loss of 17 alpha-hydroxylase activity. Addition of the 17 alpha-hydroxylase inhibitor, SU-10'603, to the incubation medium prevented the degradation of P-450 by 7 alpha-thio-SL. Similarly, preincubation of testicular microsomes with anti-P-45017 alpha,lyase IgG to inhibit 17 alpha-hydroxylation, diminished the subsequent loss of P-450 caused by 7 alpha-thio-SL. The results indicate that the 17 alpha-hydroxylase catalyzes the conversion of 7 alpha-thio-SL to the reactive metabolite responsible for P-450 destruction. The accompanying loss of 17 alpha-hydroxylase activity supports the hypothesis that suicide inhibition is the mechanism involved.

Language: en

Keywords

Animals; Cytochrome P-450 Enzyme System; Enzyme Activation; Guinea Pigs; Immunologic Techniques; Male; Microsomes; NADP; Spironolactone; Steroid 17-alpha-Hydroxylase; Testis