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J Steroid Biochem Mol Biol

Title:		"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"
Author(s):		Cooke GM; Pothier F; Murphy BD;
Address:		"Department of Physiology, University of Ottawa, Ontario, Canada. gcooke@hpb.Hwc.Ca"
Journal Title:		J Steroid Biochem Mol Biol
Year:		1997
Volume:		60
Issue:		5-Jun
Page Number:		353 - 359
DOI:		10.1016/s0960-0760(96)00223-3
ISSN/ISBN:		0960-0760 (Print) 0960-0760 (Linking)
Abstract:		"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"
Keywords:		"3-Oxo-5-alpha-Steroid 4-Dehydrogenase/drug effects/*metabolism Age Factors Androstadienes/*pharmacology Animals Dose-Response Relationship, Drug Finasteride/*analogs & derivatives/pharmacology Isoenzymes/drug effects/metabolism Kinetics Male Microsomes/*e;"
Notes:		"MedlineCooke, G M Pothier, F Murphy, B D eng Comparative Study Research Support, Non-U.S. Gov't England 1997/03/01 J Steroid Biochem Mol Biol. 1997 Mar; 60(5-6):353-9. doi: 10.1016/s0960-0760(96)00223-3"