Functional Genomics Laboratory, Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, Québec City, Canada.
J Steroid Biochem Mol Biol. 2010 Oct;122(1-3):53-64. doi: 10.1016/j.jsbmb.2010.02.023. Epub 2010 Mar 3.
Sex steroids are key regulators of adipose tissue (AT) mass, determining gender-specific differences in fat distribution and accumulation. With the aim of exploring the relevance and peculiarities of androgen action in female intra-abdominal AT, we used the serial analysis of gene expression (SAGE) method to analyze the AT transcriptome in four groups of female mice: intact, ovariectomized (OVX), OVX plus dihydrotestosterone (DHT) injection at 3h or 24h before sacrifice (DHT3h, DHT24h). An average of 19555 transcript species was examined in retroperitoneal fat. We found a total of 321 transcripts differentially modulated by DHT and OVX, including 125 novel genes. Several genes involved in energy metabolism/ATP production were up-regulated by DHT, whereas important regulators of lipid metabolism were reduced. Transcripts involved in Ca(2+) uptake/release, cell signalling, cell defence and protein expression were differentially modulated by DHT. A surprising number of myogenic genes were up-regulated, including myosin light and heavy polypeptides, troponins, as well as several actin-binding proteins. These results suggest that DHT24h may have induced a myogenic-like transcriptional program in adipocytes. The present study sheds light on the distinctive female transcriptional pattern acutely induced by androgens in intra-abdominal fat, and may add new insights into the global understanding of menopausal endocrinology and its association to intra-abdominal obesity.
性激素是脂肪组织(AT)质量的关键调节剂,决定了脂肪分布和积累的性别特异性差异。为了探索雄激素在女性腹腔内脂肪组织中的作用的相关性和特殊性,我们使用基因表达序列分析(SAGE)方法分析了四组雌性小鼠的 AT 转录组:完整组、卵巢切除组(OVX)、在牺牲前 3 小时或 24 小时注射二氢睾酮(DHT)的 OVX 组(DHT3h、DHT24h)。在腹膜后脂肪中检查了平均 19555 种转录物。我们发现共有 321 种转录物受 DHT 和 OVX 调节,其中包括 125 种新基因。一些涉及能量代谢/ATP 产生的基因被 DHT 上调,而脂质代谢的重要调节剂则被下调。涉及 Ca(2+)摄取/释放、细胞信号转导、细胞防御和蛋白质表达的转录物被 DHT 差异调节。许多肌源性基因被上调,包括肌球蛋白轻链和重链多肽、肌钙蛋白以及几种肌动蛋白结合蛋白。这些结果表明,DHT24h 可能在脂肪细胞中诱导了肌源性样转录程序。本研究揭示了雄激素在女性腹腔内脂肪中急性诱导的独特转录模式,并可能为绝经后内分泌学及其与腹腔肥胖的相关性的全面理解提供新的见解。