Local androgen inactivation in abdominal visceral adipose tissue
Local androgen inactivation in abdominal visceral adipose tissue
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DOI：
10.1210/jc.2003-030535
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发表时间：
2003-12-01
影响因子：
5.8
通讯作者：
Tchernof, A
中科院分区：
文献类型：
--
作者：
Blouin, K;Richard, C;Tchernof, A
我们检测了来自醛酮还原酶（AKR）家族1C的两种酶的表达和活性，即5型17 β-羟基类固醇脱氢酶（17 β- HSD-5，AKR 1C 3）和3型3 α-羟基类固醇脱氢酶（3 α-HSD-3，AKR 1C 2）在女性皮下和网膜脂肪组织以及前脂肪细胞原代培养物中的表达和活性。17 β-HSD-5优先从无活性的肾上腺前体雄烯二酮合成睾酮，而3 α-HSD-3使双氢睾酮失活。这两种酶的mRNA在网膜和皮下隔室的脂肪组织中检测到。实时PCR定量表明3 α-HSD-3表达比17 β-HSD-5高3倍，并且两种酶的表达在sc中倾向于高于网膜贮库。因此，在前脂肪细胞原代培养物中进行的剂量-反应和时间过程实验表明，3 α-HSD活性高于17 β-HSD活性（最大速度差异为13倍）。我们测量了32名妇女的网膜和皮下脂肪组织样本中的3 α-HSD活性，分别用双能X线吸收法和CT评估了她们的身体组成和体脂分布。我们发现，通过3 α-HSD活性在网膜脂肪组织中的雄激素失活，在内脏脂肪组织积累量高的女性中显著高于内脏脂肪组织积累量低的女性（1.7倍差异; P < 0.05）。此外，网膜脂肪组织3 α-HSD活性与CT测量的内脏脂肪组织（r = 0.43; P < 0.02）和网膜脂肪细胞直径（r = 0.42; P < 0.02）正相关且显著。这些结果表明，局部雄激素失活是女性腹部脂肪组织的主要反应，在腹部内脏肥胖的存在下观察到最大的转化率。腹型肥胖妇女网膜脂肪组织中雄激素失活增加可能局部影响脂肪细胞代谢的调节。
We examined the expression and activity of two enzymes from the aldoketoreductase (AKR) family 1C, namely type 5 17beta-hydroxysteroid dehydrogenase (17beta- HSD-5, AKR1C3) and type 3 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD-3, AKR1C2) in female sc and omental adipose tissue and in preadipocyte primary cultures. 17beta-HSD-5 preferentially synthesizes testosterone from the inactive adrenal precursor androstenedione, whereas 3alpha-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 3alpha-HSD-3 expression compared with 17beta-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 3alpha-HSD activity was higher than 17beta-HSD activity (13-fold maximum velocity difference). We measured 3alpha-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 3alpha-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 alpha-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.