PMID- 11061520
OWN - NLM
STAT- MEDLINE
DCOM- 20001115
LR  - 20131121
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 85
IP  - 10
DP  - 2000 Oct
TI  - 3beta-hydroxysteroid dehydrogenase/delta5-->4-isomerase activity associated with 
      the human 17beta-hydroxysteroid dehydrogenase type 2 isoform.
PG  - 3669-72
AB  - The type 2 isoform of human 17beta-hydroxysteroid dehydrogenase (17betaHSD2) 
      efficiently catalyzes the oxidative metabolism of androgens and estrogens, and it 
      is expressed in a large series of human peripheral tissues. To obtain a better 
      understanding of the regulation of local steroid biosynthesis and metabolism in 
      human tissues, we have established a dual steroidogenic activity of the 
      17betaHSD2 enzyme after transfection of human 17betaHSD2-transfected human 
      embryonic kidney (293) cells. After transient transfection, the metabolism of 
      testosterone, pregnenolone, and dehydroepiandrosterone (DHEA) in intact 
      transfected 293 cells was evaluated by TLC-based radiometric assays. 
      17betaHSD2-transfected cells converted 91% of testosterone (1 micromol/L) into 
      androstenedione in a 2-h incubation period. In addition, pregnenolone (1 
      micromol/L) was converted to progesterone (18.5%), whereas DHEA (1 micromol/L) 
      was metabolized to androstenedione (8.3% conversion) in a 15-h incubation period. 
      The kinetics of the 3beta-hydroxysteroid dehydrogenase (3betaHSD) and 17betaHSD2 
      activities using cell homogenate protein of stably transfected 293 cells 
      indicated that the catalytic efficiency (apparent catalytic efficiency = maximum 
      velocity/Km) of this 3betaHSD activity is approximately 2000-fold (pregnenolone 
      as substrate) or 3000-fold (DHEA as substrate) weaker than that of 17betaHSD2 
      activity. It is noteworthy, however, that the apparent catalytic efficiency of 
      the HSD3B2 gene product is only approximately 50-fold higher than that of the 
      3betaHSD aspect of the 17betaHSD2 gene product. Pregnenolone or DHEA effectively 
      inhibited 17betaHSD2 activity in a noncompetitive fashion. Furthermore, the 
      potent 5alpha-reductase/3betaHSD inhibitor, 
      17beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5alpha-androstane-3-one , inhibited 
      neither 3betaHSD nor 17betaHSD2 activities. We conclude that human 17betaHSD2 
      enzyme exhibits 3betaHSD activity. Notwithstanding that this 3betaHSD activity is 
      reduced compared to 17betaHSD oxidative activity, it may account for at least 
      some of the reports of 3betaHSD activity found in human peripheral tissues that 
      express notable amounts of the 17betaHSD2 isozyme as well as in individuals with 
      severe classic 3betaHSD deficiency.
FAU - Suzuki, T
AU  - Suzuki T
AD  - Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
FAU - Sasano, H
AU  - Sasano H
FAU - Andersson, S
AU  - Andersson S
FAU - Mason, J I
AU  - Mason JI
LA  - eng
GR  - DK-52167/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Hormones)
RN  - 0 (Isoenzymes)
RN  - 3XMK78S47O (Testosterone)
RN  - EC 1.1.- (17-Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.- (20-Hydroxysteroid Dehydrogenases)
SB  - IM
MH  - 17-Hydroxysteroid Dehydrogenases/genetics/*metabolism
MH  - 20-Hydroxysteroid Dehydrogenases/genetics/*metabolism
MH  - Genetic Vectors
MH  - Hormones/metabolism
MH  - Humans
MH  - Isoenzymes/genetics/metabolism
MH  - Kidney/cytology/metabolism
MH  - Kinetics
MH  - Plasmids/genetics
MH  - Testosterone/metabolism
EDAT- 2000/11/04 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/11/04 11:00
PHST- 2000/11/04 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/04 11:00 [entrez]
AID - 10.1210/jcem.85.10.6918 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2000 Oct;85(10):3669-72. doi: 10.1210/jcem.85.10.6918.