Transcriptomic analysis of MA-10 tumor Leydig cells treated with adipose derived hormones adiponectin and resistin

Abstract

Obesity contributes to a decrease in testosterone production in men. Indeed, adipose tissue produces several hormones, including adiponectin and resistin, and these may influence the activity of signaling pathways responsible for regulating the expression of genes related to steroidogenesis. In this study, we wanted to identify which genes are directly regulated by these hormones using the MA-10 tumor Leydig cell model. To do this, we treated these cells with adiponectin or resistin, followed by RNA extraction and RNA-Seq transcriptome analysis. Interestingly, genes upregulated by the globular form of adiponectin (gACRP30) were associated to steroid hormones biosynthesis, whereas resistin had no effect on the transcriptome of MA-10 Leydig cells. Moreover, the expression of the Star gene, encoding the steroidogenic acute regulatory protein, was increased in response to treatments with 0.5 mM 8Br-cAMP. Such stimulation was further increased by adiponectin, resulting in increased progesterone production. However, resistin had no effect on steroid production from MA-10 tumor Leydig cells under the treatment conditions investigated. Thus, our data suggest that a direct regulation of steroidogenic genes' expressions in Leydig cells by adipose derived hormones involves cooperation between the cAMP/PKA pathway and adiponectin, but not resistin, to activate Star expression and improve progesterone synthesis.