The effects of progesterone, 4,16-androstadien-3-one and MK-434 on the kinetics of pig testis microsomal testosterone-4-ene-5alpha-reductase activity.
The enzyme 3-oxo-steroid: NADP+ 4-oxidoreductase (EC 1.3.1.22; 5alpha-reductase) was assayed in testicular microsomes of pigs of 3, 20 and 24 weeks of age. The activity was very low in 3-week-old animals and approximately 10-fold higher in 5- and 6-month-old pigs. The pH optimum was 6.3 in 6-month-old animals, 5.7 in 5-month-old animals, but could not be reliably determined in 3-week-old animals. The kinetic parameters for 5alpha-reductase in testis microsomes from 6-month-old animals were; K((m)(app)), 8.0 micromol/l, V((max)(app)), 6.7 nmoles/90 min/mg protein. Progesterone was a competitive inhibitor of testosterone 5alpha-reduction with an apparent K((i)(app)) of 0.86 micromol/l. However, 4,16-androstadien-3-one (dienone), which undergoes 5alpha-reduction in the biosynthesis of the pheromonally active 16-androstenes, was a comparatively poor inhibitor with a K((i)(app)) of 4.9 micromol/l. Similarly, MK434, which is a selective inhibitor of the human type 2 5alpha-reductase, but which inhibits both types 1 and 2 in the rat, was also a poor competitive inhibitor of testosterone 5alpha-reductase in the pig testis (K((i)(app)), 3.1 micromol/l). It would appear from these studies that the pig testis microsomal 5alpha-reductase corresponds to a type 1 isozyme that is not capable of reducing dienone other than under conditions where the dienone concentration would be in considerable excess of testosterone. It is, therefore, probable that substrate-specific 5alpha-reductases exist in the pig testis for the 5alpha-reduction of testosterone and dienone.
Cooke
G M
GM
Department of Physiology, University of Ottawa, Ontario, Canada. gcooke@hpb.Hwc.Ca
Pothier
F
F
Murphy
B D
BD
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000187:drug effects / Q000378:metabolism*; D000367:Age Factors; D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D018120:Finasteride / Q000031:analogs & derivatives* / Q000494:pharmacology; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000201:enzymology*; D011374:Progesterone / Q000494:pharmacology; D013379:Substrate Specificity; D013552:Swine; D013737:Testis / Q000201:enzymology*
C088478:17 beta-benzoyl-4-aza-5 alpha-androst-1-ene-3-one; D000730:Androstadienes; D007527:Isoenzymes; C003524:4,16-androstadien-3-one; D011374:Progesterone; D018120:Finasteride; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase