Submitted on January 21, 2008
Accepted on October 20, 2008
Pathways of Adipose Tissue Androgen Metabolism in Women: Depot Differences and Modulation by Adipogenesis
Karine Blouin1, Melanie Nadeau2, Jacques Mailloux3, Marleen Daris4, Stephane Lebel5, Van Luu-The2, and Andre Tchernof6*
1 Molecular Endocrinology, Laval University Medical Research Center, Quebec City, Canada
2 Molecular Endocrinology, Laval University Medical Research Center, Quebec City, Canada; Quebec City, Canada
3 Gynecology Unit, Laval University Medical Research Center, Quebec City, Canada
4 Quebec City, Canada; Gynecology Unit, Laval University Medical Research Center, Quebec City, Canada
5 Department of Surgery, Laval University, Quebec City, Canada
6 Molecular Endocrinology Laboratory, Laval University Medical Center, Quebec City, United States
* To whom correspondence should be addressed. E-mail: andre.tchernof{at}crchul.ulaval.ca.
The objective was to examine pathways of androgen metabolism in abdominal adipose tissue in women. Abdominal subcutaneous (SC) and omental (OM) adipose tissue samples were surgically obtained in women. Total RNA was isolated from whole adipose tissue samples and from primary preadipocyte cultures before and after induction of differentiation. Expression levels of several steroid-converting enzyme transcripts were examined by real-time RT-PCR. Androgen inactivation rates were also measured. We found higher expression levels in SC compared to OM adipose tissue for type 1 3
-hydroxysteroid dehydrogenase (3-HSD-1) (p<0.05), for aldo-keto reductase 1C3 (AKR1C3) (p<0.0001), for AKR1C2 (p<0.0001) and for the androgen receptor (p<0.0001). 17-HSD-2 mRNA levels were lower in SC adipose tissue (p<0.05). Induction of adipocyte differentiation led to significantly increased expression levels in SC cultures for AKR1C3 (4.7-fold, p<0.01), 11-cis-retinol dehydrogenase (6.9-fold, p<0.02), AKR1C2 (5.6-fold, p<0.004), P450 aromatase (5.7-fold, p<0.02), steroid sulfatase (3.1-fold, p<0.02), estrogen receptor- (11.8-fold, p<0.01) and the androgen receptor (4.0-fold, p<0.0005). Generally similar, but non-significant trends were obtained in OM cultures. DHT inactivation rates increased with differentiation, this effect being mediated by dexamethasone alone, through a glucocorticoid receptor-dependent mechanism. In conclusion, higher mRNA levels of enzymes synthesizing and inactivating androgens are found in differentiated adipocytes, consistent with higher androgen processing rates in these cells. Glucocorticoid-induced androgen inactivation may locally modulate the exposure of adipose cells to active androgens.
