PMID- 18252781
OWN - NLM
STAT- MEDLINE
DCOM- 20080527
LR  - 20220331
IS  - 0021-972X (Print)
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 93
IP  - 4
DP  - 2008 Apr
TI  - 3alpha-Hydroxysteroid dehydrogenase type III deficiency: a novel mechanism for 
      hirsutism.
PG  - 1298-303
LID - 10.1210/jc.2007-2708 [doi]
AB  - CONTEXT: Dihydrotestosterone (DHT), the primary active androgen in peripheral 
      target tissues, is metabolized by 3alpha-hydroxysteroid dehydrogenase type III 
      (3alpha-HSD), encoded by the AKR1C2 gene, forming 
      5alpha-androstane-3alpha,17beta-diol (3alpha-diol). 3alpha-HSD may play a role in 
      the pathogenesis of hirsutism. OBJECTIVES: Our objective was to evaluate the role 
      of 3alpha-HSD in hirsutism by comparing 1) tissue levels of active androgens, 2) 
      relative gene expression of AKR1C2, and 3) activity of 3alpha-HSD in genital skin 
      from normal and hirsute women. DESIGN: Genital skin was obtained from normal and 
      hirsute women. After homogenization, testosterone (T) and DHT levels were 
      quantified by conventional RIA. From isolated RNA, relative expression of AKR1C2 
      was determined by real-time PCR. In addition, minced genital skin was incubated 
      with [(3)H]DHT, and the product, [(3)H]3alpha-diol, was quantified by radio-HPLC. 
      SETTING: The study took place at an inner-city hospital. PATIENTS: PATIENTS 
      included women undergoing posterior colporrhaphy. MAIN OUTCOME MEASURES: We 
      assessed 1) tissue levels of T, DHT, and 3alpha-diol; 2) relative expression of 
      AKR1C2; and 3) conversion ratio of [(3)H]3alpha-diol to [(3)H]DHT. RESULTS: In 
      genital skin, tissue DHT and T concentrations in hirsute women were 1.90-fold and 
      1.84-fold higher than in normal women (P =0 .002 and 0.03), and relative 
      expression of AKR1C2 mRNA was reduced approximately 7-fold (P = 0.04). Genital 
      skin from hirsute women showed less metabolism of [(3)H]DHT to [(3)H]3alpha-diol 
      (conversion ratio, 0.24 +/- 0.19 vs. 0.85 +/- 0.55, P = 0.01). CONCLUSIONS: In 
      genital skin of hirsute women, reduced AKR1C2 gene expression and 3alpha-HSD 
      activity results in decreased DHT metabolism and elevated tissue levels of DHT. 
      Diminished DHT metabolism may play an important role in the pathogenesis of 
      hirsutism.
FAU - Steiner, Anne Z
AU  - Steiner AZ
AD  - Department of Obstetrics and Gynecology, University of North Carolina, Chapel 
      Hill, North Carolina 27599, USA. asteiner@med.unc.edu
FAU - Chang, Lilly
AU  - Chang L
FAU - Ji, Qing
AU  - Ji Q
FAU - Ookhtens, Murad
AU  - Ookhtens M
FAU - Stolz, Andrew
AU  - Stolz A
FAU - Paulson, Richard J
AU  - Paulson RJ
FAU - Stanczyk, Frank Z
AU  - Stanczyk FZ
LA  - eng
GR  - P30 DK048522/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20080205
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (RNA, Messenger)
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.357 (AKR1C2 protein, human)
RN  - EC 1.1.1.50 (3-alpha-Hydroxysteroid Dehydrogenase (B-Specific))
SB  - IM
MH  - 3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)/*deficiency
MH  - Adult
MH  - Dihydrotestosterone/metabolism
MH  - Female
MH  - Hirsutism/enzymology/*etiology
MH  - Humans
MH  - Hydroxysteroid Dehydrogenases/genetics
MH  - Middle Aged
MH  - RNA, Messenger/analysis
PMC - PMC2291485
EDAT- 2008/02/07 09:00
MHDA- 2008/05/28 09:00
PMCR- 2009/04/01
CRDT- 2008/02/07 09:00
PHST- 2008/02/07 09:00 [pubmed]
PHST- 2008/05/28 09:00 [medline]
PHST- 2008/02/07 09:00 [entrez]
PHST- 2009/04/01 00:00 [pmc-release]
AID - jc.2007-2708 [pii]
AID - 5729 [pii]
AID - 10.1210/jc.2007-2708 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2008 Apr;93(4):1298-303. doi: 10.1210/jc.2007-2708. Epub 
      2008 Feb 5.