Modulation of the transcriptomic profile of the R2C tumor Leydig cell line by the adipose tissue derived hormone leptin

Abstract

Leptin is an important adipose derived hormone being secreted by adipocytes and involved in appetite regulation. Disruption of normal plasma levels of leptin has been associated with the pathogenesis of obesity. It is now well established that obesity is associated to an increased risk of cancer development, including testicular cancers. Recently, we have shown that high levels of leptin have inhibitory effects on cAMP-dependent steroidogenic genes expression in MA-10 Leydig cells. Hence, we examined if leptin could alter the transcriptome of the constitutively steroidogenic rat tumor Leydig cell line R2C. These cells were treated with high levels of leptin (1000 ng/ml) for 4 h, followed by mRNA extraction and RNA-Seq analysis. Interestingly, leptin had no effect on steroidogenic gene expression or pathways promoting tumorigenesis of this cell line. Genes being upregulated or downregulated by leptin were enriched in biological processes that were non-relevant to Leydig cell function. Surprisingly, lepr isoforms were weakly expressed in R2C cells and may explain in part the low levels of leptin’s response for tumor Leydig cells. Hence, the current findings suggest that acute treatments of tumor Leydig cells with high levels of leptin have negligible effects on transcriptomics and rather supports that leptin would have a central effect on the hypothalamus to influence testicular function.