Pathways of adipose tissue androgen metabolism in women: depot differences and modulation by adipogenesis

被引:75
作者
Blouin, Karine [1 ,2 ]
Nadeau, Melanie [1 ]
Mailloux, Jacques [4 ]
Daris, Marleen [4 ]
Lebel, Stephane [3 ]
Van Luu-The [1 ]
Tchernof, Andre [1 ,2 ]
机构
[1] Univ Laval, Med Res Ctr, Mol Endocrinol & Oncol Res Ctr, Quebec City, PQ G1V 4G2, Canada
[2] Univ Laval, Dept Nutr, Quebec City, PQ G1V 4G2, Canada
[3] Univ Laval, Dept Surg, Quebec City, PQ G1V 4G2, Canada
[4] Univ Laval, Med Res Ctr, Gynecol Unit, Quebec City, PQ G1V 4G2, Canada
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 2009年 / 296卷 / 02期
基金
加拿大健康研究院;
关键词
aldo-keto reductases; short-chain dehydrogenases; adipocyte differentiation; omental visceral fat; estrogen; ESTROGEN-RECEPTOR-BETA; HUMAN PREADIPOCYTES; 3-ALPHA-HYDROXYSTEROID DEHYDROGENASES; 20-ALPHA-HYDROXYSTEROID DEHYDROGENASE; AROMATASE-ACTIVITY; GENE-EXPRESSION; STROMAL CELLS; DIFFERENTIATION; OBESITY; 17-BETA-HYDROXYSTEROID-DEHYDROGENASE;
D O I
10.1152/ajpendo.00039.2008
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Blouin K, Nadeau M, Mailloux J, Daris M, Lebel S, Luu-The V, Tchernof A. Pathways of adipose tissue androgen metabolism in women: depot differences and modulation by adipogenesis. Am J Physiol Endocrinol Metab 296: E244-E255, 2009. First published November 4, 2008; doi: 10.1152/ajpendo.00039.2008.-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 conversion rates were also measured. We found higher expression levels in SC compared with OM adipose tissue for type 1 3 beta-hydroxysteroid dehydrogenase (3 beta-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 beta-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), P-450 aromatase (5.7-fold, P < 0.02), steroid sulfatase (3.1-fold, P < 0.02), estrogen receptor-beta (11.8-fold, P < 0.01), and the androgen receptor (4.0-fold, P < 0.0005). Generally similar but nonsignificant 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.
引用
收藏
页码:E244 / E255
页数:12
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