MacKenzie Scott M, Huda Shahzya S, Sattar Naveed, Fraser Robert, Connell John M C, Davies Eleanor
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
Clin Endocrinol (Oxf). 2008 Dec;69(6):848-54. doi: 10.1111/j.1365-2265.2008.03262.x. Epub 2008 Apr 10.
Sex steroids (androgens and oestrogens) and corticosteroids (glucocorticoids and mineralocorticoids) have a major impact on fat distribution. Several genes involved in steroid synthesis and metabolism, such as 11beta-hydroxysteroid dehydrogenase type 1 and aromatase, are known to be expressed within adipose tissue, thus modulating local steroid levels; however, our knowledge of which genes are expressed and at what level is incomplete.
To detect by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) which of 13 key steroidogenic genes are transcribed within human adipose tissue and to assess whether mRNA levels differ significantly between the subcutaneous abdominal and omental adipose depots.
Eight women undergoing caesarean section [age 29.1 +/- 6.5 years, body mass index (BMI) 28.9 +/- 8.4 kg/m(2)].
Genes transcribed in both depots were StAR (steroidogenic acute regulatory protein), CYP11A1 (side-chain cleavage enzyme), HSD3B2 (3beta-hydroxysteroid dehydrogenase type 2), CYP21B (21-hydroxylase), CYP19 (aromatase), HSD11B1 (11beta-hydroxysteroid dehydrogenase type 1), HSD17B3, HSD17B5, HSD17B7 (17beta-hydroxysteroid dehydrogenase types 3, 5 and 7) and SRD5A2 (5alpha-reductase type 2). All but SRD5A2 varied significantly in abundance between depots. CYP17 (17alpha-hydroxylase), CYP11B1 (11beta-hydroxylase) and CYP11B2 (aldosterone synthase) transcription were not detected.
This study confirms and significantly extends our knowledge of steroidogenic gene expression within adipose tissue, showing that transcript levels are depot specific. We have demonstrated that de novo synthesis from cholesterol of sex steroids, cortisol and aldosterone is not possible because of the absence of key steroidogenic mRNAs. Instead, the pattern of transcription suggests that 11-deoxycorticosterone, a mineralocorticoid, would be the ultimate product of any de novo adipose synthesis.
性类固醇(雄激素和雌激素)和皮质类固醇(糖皮质激素和盐皮质激素)对脂肪分布有重大影响。已知一些参与类固醇合成和代谢的基因,如11β-羟基类固醇脱氢酶1型和芳香化酶,在脂肪组织中表达,从而调节局部类固醇水平;然而,我们对于哪些基因表达以及表达水平如何的了解并不完整。
通过实时定量逆转录聚合酶链反应(qRT-PCR)检测13个关键类固醇生成基因中哪些在人体脂肪组织中转录,并评估皮下腹部脂肪库和网膜脂肪库之间的mRNA水平是否存在显著差异。
8名接受剖宫产的女性[年龄29.1±6.5岁,体重指数(BMI)28.9±8.4kg/m²]。
在两个脂肪库中转录的基因有类固醇生成急性调节蛋白(StAR)、细胞色素P450侧链裂解酶(CYP11A1)、3β-羟基类固醇脱氢酶2型(HSD3B2)、21-羟化酶(CYP21B)、芳香化酶(CYP19)、11β-羟基类固醇脱氢酶1型(HSD11B1)、17β-羟基类固醇脱氢酶3型(HSD17B3)、17β-羟基类固醇脱氢酶5型(HSD17B5)、17β-羟基类固醇脱氢酶7型(HSD17B7)和5α-还原酶2型(SRD5A2)。除SRD5A2外,所有基因在不同脂肪库中的丰度均有显著差异。未检测到17α-羟化酶(CYP17)、11β-羟化酶(CYP11B1)和醛固酮合酶(CYP11B2)的转录。
本研究证实并显著扩展了我们对脂肪组织中类固醇生成基因表达的认识,表明转录水平具有脂肪库特异性。我们已经证明,由于关键类固醇生成mRNA的缺失,从胆固醇从头合成性类固醇、皮质醇和醛固酮是不可能的。相反,转录模式表明,一种盐皮质激素11-脱氧皮质酮将是任何脂肪从头合成的最终产物。