期刊
MOLECULAR AND CELLULAR BIOCHEMISTRY
卷 433, 期 1-2, 页码 79-95出版社
SPRINGER
DOI: 10.1007/s11010-017-3017-x
关键词
Leptin; Lepr; Ob-R; Steroidogenesis; Star; Cyp11a1; Leydig cells
类别
资金
- Natural Sciences and Engineering Research Council (NSERC) of Canada [386557-2012]
- New Brunswick Health Research Foundation (NBHRF) [2010-SEED-178, 2013-OG]
- New Brunswick Innovation Foundation (NBIF) [IAR2012, IAR2013-029]
The adipose tissue is an important endocrine organ secreting numerous peptide hormones, including leptin. Increased circulating levels of leptin, as a result of hormonal resistance in obese individuals, may contribute to lower androgen production in obese males. However, the molecular mechanisms involved need to be better defined. Androgens are mainly produced by Leydig cells within the testis. In male rodents, activation of the leptin receptor modulates a cascade of intracellular signal transduction pathways which may lead to regulation of transcription factors having influences on steroidogenesis in Leydig cells. Thus, as a result of high leptin levels interacting with its receptor and modulating the activity of the JAK/STAT signaling pathway, the activity of transcription factors important for steroidogenic genes expressions may be inhibited in Leydig cells. Here we show that Lepr is increasingly expressed within Leydig cells according to postnatal development. Although high levels of leptin (corresponding to obesity condition) alone had no effect on Leydig cells' steroidogenic genes expression, it downregulated cAMP-dependent activations of the cholesterol transporter Star and of the rate-limiting steroidogenic enzyme Cyp11a1. Our results suggest that STAT transcriptional activity is downregulated by high levels of leptin, leading to reduced cAMP-dependent steroidogenic genes (Star and Cyp11a1) expressions in MA-10 Leydig cells. However, other transcription factors such as members of the SMAD and NFAT families may be involved and need further investigation to better define how leptin regulates their activities and their relevance for Leydig cells function.
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