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Local Androgen Inactivation in Abdominal Visceral Adipose Tissue

Molecular Endocrinology and Oncology Research Center (K.B., C.R., C.B., V.L.-T., A.T.), and Gynecology Unit (P.D., M.D., P.L.), Laval University Medical Research Center, Québec, Canada G1V 4G2

Address all correspondence and requests for reprints to: André Tchernof, Ph.D., Molecular Endocrinology and Oncology Research Center, Laval University Medical Research Center, 2705 Laurier Boulevard (T3-67), Québec, PQ, Canada G1V 4G2. E-mail: andre.tchernof{at}crchul.ulaval.ca.

We examined the expression and activity of two enzymes from the aldoketoreductase (AKR) family 1C, namely type 5 17ß-hydroxysteroid dehydrogenase (17ß-HSD-5, AKR1C3) and type 3 3-hydroxysteroid dehydrogenase (3-HSD-3, AKR1C2) in female sc and omental adipose tissue and in preadipocyte primary cultures. 17ß-HSD-5 preferentially synthesizes testosterone from the inactive adrenal precursor androstenedione, whereas 3-HSD-3 inactivates dihydrotestosterone. mRNAs of both enzymes were detected in adipose tissue from the omental and sc compartments. Real-time PCR quantification indicated a 3-fold higher 3-HSD-3 expression compared with 17ß-HSD-5, and the expression of both enzymes tended to be higher in the sc vs. the omental depot. Accordingly, dose-response and time-course experiments performed in preadipocyte primary cultures indicated that 3-HSD activity was higher than 17ß-HSD activity (13-fold maximum velocity difference). We measured 3-HSD activity in omental and sc adipose tissue samples of 32 women for whom body composition and body fat distribution were evaluated by dual-energy x-ray absorptiometry and CT, respectively. We found that androgen inactivation in omental adipose tissue through 3-HSD activity was significantly higher in women with elevated vs. low visceral adipose tissue accumulation (1.7-fold difference; P < 0.05). Moreover, omental adipose tissue 3-HSD activity was positively and significantly associated with CT-measured visceral adipose tissue (r = 0.43; P < 0.02) and omental adipocyte diameter (r = 0.42; P < 0.02). These results indicate that local androgen inactivation is a predominant reaction in female abdominal adipose tissue, with the greatest conversion rates observed in the presence of abdominal visceral obesity. Increased androgen inactivation in omental adipose tissue of abdominally obese women may impact locally on the regulation of adipocyte metabolism.

This study was supported by the Canadian Diabetes Association and the Canadian Institutes of Health Research. A.T. is the recipient of a Scholarship from the Fonds de la Recherche en Santé du Québec. K.B. is the recipient of a Québec Diabetes Association summer studentship and a Fonds de la Recherche en Santé du Québec fellowship.

Abbreviations: AKR, Aldoketoreductase; CT, computed tomography; DHT, dihydrotestosterone; HDL, high-density lipoprotein; HSD, hydroxysteroid dehydrogenase; KRH, Krebs-Ringer-Henseleit; LDL, low-density lipoprotein; UGT, UDP-glucuronosyltransferase.

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