Cadagan David, Khan Raheela, Amer Saad
School of Graduate Entry Medicine, Derby Hospital, Nottingham University, DE22 3DT, UK.
Mol Genet Metab Rep. 2014 Jun 29;1:254-263. doi: 10.1016/j.ymgmr.2014.05.002. eCollection 2014.
The metabolic syndrome is a cluster of metabolic disorders characterized by insulin resistance and hyperinsulinaemia, and its presence can increase the risk of cardiovascular disease significantly. The metabolic syndrome is associated with increased circulating androgen levels in women, which may originate from the ovaries and adrenal glands. Adipocytes are also able to synthesise steroid hormones, and this output has been hypothesised to increase with elevated insulin plasma concentrations. However, the contribution of the adipocytes to the circulating androgen levels in women with metabolic syndrome is limited and the effects of insulin are not fully understood. The aim of this study was to investigate the presence of steroid precursors and synthetic enzymes in human adipocyte biopsies as markers of possible adipocyte androgen synthesis. We examined pre and mature adipocytes taken from tissue biopsies of abdominal subcutaneous adipose tissue of participating women from the Department of Obstetrics and Gynaecology, of the Royal Derby Hospital. The results showed the potential for localised adipocyte androgen synthesis through the presence of the androgen precursor progesterone, as well as the steroid-converting enzyme 17α-hydroxylase. Furthermore, we found the controlled secretion of androstenedione and that insulin treatment caused levels to increase. Continued examination of a localised source of androgen production is therefore of clinical relevance due to its influence on adipocyte metabolism, its negative impact on female steroidogenic homeostasis, and the possible aggravation this may have when associated to obesity and obesity related metabolic abnormalities such as hyperinsulinaemia.
代谢综合征是一组以胰岛素抵抗和高胰岛素血症为特征的代谢紊乱症，其存在会显著增加心血管疾病的风险。代谢综合征与女性循环雄激素水平升高有关，这些雄激素可能来源于卵巢和肾上腺。脂肪细胞也能够合成类固醇激素，并且据推测，随着血浆胰岛素浓度升高，这种产出会增加。然而，脂肪细胞对患有代谢综合征女性循环雄激素水平的贡献有限，胰岛素的作用也尚未完全了解。本研究的目的是调查人类脂肪细胞活检中类固醇前体和合成酶的存在情况，作为脂肪细胞雄激素合成可能性的标志物。我们检查了从皇家德比医院妇产科参与研究的女性腹部皮下脂肪组织活检中获取的前脂肪细胞和成熟脂肪细胞。结果显示，通过雄激素前体孕酮以及类固醇转化酶17α - 羟化酶的存在，脂肪细胞具有局部合成雄激素的潜力。此外，我们发现了雄烯二酮的可控分泌，并且胰岛素治疗会导致其水平升高。因此，由于局部雄激素产生源对脂肪细胞代谢的影响、对女性类固醇生成稳态的负面影响以及与肥胖和肥胖相关代谢异常（如高胰岛素血症）相关时可能产生的加重作用，持续研究其临床意义重大。
