Inhibition of testicular microsomal cytochrome P-450 (17 alpha-hydroxylase/C-17,20-lyase) by estrogens

Endocrinology
M Onoda, P F Hall

Abstract

Highly purified cytochrome P-450 from neonatal pig testicular microsomes is capable of catalyzing both 17 alpha-hydroxylation and C-17,20-lyase activity. Estradiol was found to inhibit both activities of the purified enzyme with delta 4 and with delta 5 substrates (progesterone, pregnenolone, and the corresponding 17 alpha-hydroxysteroids). For the delta 4 series, inhibition of lyase is competitive and that of 17 alpha-hydroxylase is noncompetitive; for the delta 5 series, inhibition was noncompetitive for both activities. Ki values for lyase activity were determined from enzyme kinetics (5.0 microM for the delta 4 substrate and 20 microM for the delta 5 substrate). Estradiol produces a typical type I spectral shift with the pure enzyme (Ks = 3.0 microM where Ks is the concentration of steroid required to give half maximal spectral shift), so that Ki values were also determined directly from binding studies by using substrate-induced difference spectroscopy. Fifty per cent inhibition of the maximal spectral shift induced by the 17 alpha-hydroxysubstrates (Ki) are 3.8 and 7.6 microM for the delta 4 and delta 5 substrates, respectively. Values for Ki are higher with the substrates of 17 alpha-hydroxylase (progesterone and pregnen...Continue Reading

Citations

May 1, 1997·Indian Journal of Pediatrics·A C AmminiM Vijayaraghavan
Oct 1, 1983·Journal of Steroid Biochemistry·D B Gower, G M Cooke
Dec 1, 1984·Journal of Steroid Biochemistry·D B Hales, G Betz
Dec 1, 1986·Journal of Steroid Biochemistry·P G Quinn, A H Payne
Nov 1, 1982·Molecular and Cellular Endocrinology·M BenahmedJ M Saez
Jun 1, 1995·The Journal of Steroid Biochemistry and Molecular Biology·M Zachmann
Nov 14, 2003·Reproductive Toxicology·Srinivasan RengarajanKarundevi Balasubramanian
Feb 19, 2003·The Journal of Steroid Biochemistry and Molecular Biology·P ParteH S Juneja
Jan 28, 2012·Reproduction, Fertility, and Development·Ming LiuYan-ling Wang
Jan 1, 1993·European Journal of Pediatrics·M Zachmann
Mar 1, 1985·Journal of Steroid Biochemistry·E M BernsH J van der Molen
Nov 1, 2007·Environmental Toxicology and Pharmacology·Seiichi YoshidaKen Takeda
Jun 7, 2008·Journal of Experimental Zoology. Part A, Ecological Genetics and Physiology·Nanna Brande-LavridsenBodil Korsgaard
Jul 29, 2006·General and Comparative Endocrinology·B Scott Nunez, Scott L Applebaum
Feb 15, 2001·The Journal of Urology·C P PavlovichP N Schlegel
Jan 9, 2003·The Urologic Clinics of North America·Farjaad M Siddiq, Mark Sigman
Sep 24, 2010·Journal of Biomedicine & Biotechnology·K SvechnikovO Söder
Jan 1, 1986·Scandinavian Journal of Urology and Nephrology·L DaehlinF Petersson
May 28, 1993·Annals of the New York Academy of Sciences·R L RosenfieldZ Sheikh
Jun 16, 2001·Endocrine Reviews·L O'DonnellE R Simpson
Jul 11, 2020·Therapeutic Advances in Reproductive Health·Nader Salama, Saeed Blgozah
Jan 14, 1986·Biochemical and Biophysical Research Communications·J L Taft, R G Larkins
May 10, 2001·Endocrinology and Metabolism Clinics of North America·R J Auchus

❮ Previous
Next ❯

Related Concepts

Related Feeds

Biosynthetic Transformations

Biosyntheic transformtions are multi-step, enzyme-catalyzed processes where substrates are converted into more complex products in living organisms. Simple compounds are modified, converted into other compounds, or joined together to form macromolecules. Discover the latest research on biosynthetic transformations here.