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This version published online on February 5, 2008
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-2708
A more recent version of this article appeared on April 1, 2008
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Right arrow Female Endocrinology

Submitted on December 7, 2007
Accepted on January 25, 2008

3{alpha}-Hydroxysteroid Dehydrogenase Type III Deficiency: A Novel Mechanism for Hirsutism

Anne Z. Steiner MD, MPH*, Lilly Chang MD, Qing Ji PhD, Murad Ookhtens PhD, Andrew Stolz MD, Richard J. Paulson MD, and Frank Z. Stanczyk PhD

Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA; Department of Obstetrics and Gynecology, University of Southern California Keck School of Medicine, Los Angeles, California, USA; Department of Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, USA

* To whom correspondence should be addressed. E-mail: asteiner{at}med.unc.edu.

Context: Dihydrotestosterone (DHT), the primary active androgen in peripheral target tissues, is metabolized by 3{alpha}-hydroxysteroid dehydrogenase type III (3{alpha}-HSD), encoded by the AKR1C2 gene, forming 5{alpha}-androstane-3{alpha}, 17{beta}-diol (3{alpha}-diol). 3{alpha}-HSD may play a role in the pathogenesis of hirsutism.

Objectives: To evaluate the role of 3{alpha}-HSD in hirsutism by comparing 1) tissue levels of active androgens, 2) relative gene expression of AKR1C2, and 3) activity of 3{alpha}-HSD in genital skin from normal and hirsute women.

Design: Genital skin was obtained from normal and hirsute women. Following homogenization, testosterone (T) and DHT levels were quantified by conventional radioimmunoassay. From isolated RNA, relative expression of AKR1C2 was determined by real time PCR. In addition, minced genital skin was incubated with 3H-DHT, and the product, 3H-3{alpha}-diol, was quantified by radio-HPLC.

Setting: Inner-city hospital.

Patients: Women undergoing posterior colporrhaphy.

Intervention: None.

Main Outcome Measures: 1) Tissue levels of T, DHT, and 3{alpha}-diol, 2) relative expression of AKR1C2, 3) conversion ratio of 3H-3{alpha}-diol to 3H-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 3H-DHT to 3H-3{alpha}-diol (conversion ratio, 0.24±0.19 versus 0.85±0.55, p=0.01).

Conclusions: In genital skin of hirsute women, reduced AKR1C2 gene expression and 3{alpha}-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.
Key words: hirsutism • androgens • 3a-hydroxysteroid dehydrogenase






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