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

J Steroid Biochem Mol Biol. 1997 Mar;60(5-6):353-9. doi: 10.1016/s0960-0760(96)00223-3.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / drug effects
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / metabolism*
  • Age Factors
  • Androstadienes / pharmacology*
  • Animals
  • Dose-Response Relationship, Drug
  • Finasteride / analogs & derivatives*
  • Finasteride / pharmacology
  • Isoenzymes / drug effects
  • Isoenzymes / metabolism
  • Kinetics
  • Male
  • Microsomes / enzymology*
  • Progesterone / pharmacology
  • Substrate Specificity
  • Swine
  • Testis / enzymology*

Substances

  • 17 beta-benzoyl-4-aza-5 alpha-androst-1-ene-3-one
  • Androstadienes
  • Isoenzymes
  • 4,16-androstadien-3-one
  • Progesterone
  • Finasteride
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase