The Role of Specific Mitogen-Activated Protein Kinase Signaling Cascades in the Regulation of Steroidogenesis

Figure 1

A schematic model illustrating the involvement of multiple signaling in MAPK-mediated regulation of StAR expression and steroidogenesis. Interaction of trophic hormones with their specific membrane receptors results in the activation of G proteins (G), which, in turn, stimulate adenylate cyclase (AC) that catalyzes the production of cAMP from ATP. cAMP then activates PKA and results in the phosphorylation of transcription factors involved in StAR gene transcription. The binding of growth factors results in activation of receptor tyrosine kinase and mediates biological functions via a number of mechanisms, including receptor autophosphorylation, receptor clustering, and phosphorylation of intracellular proteins. This leads to the activation of a cascade of protein kinases including Ras/Raf, and other related kinases. These protein kinases, in turn, activate different transcription factors, including CREB/ATF-1, cFos, and cJun. Phosphorylation of these transcription factors results in the transcriptional regulation of the StAR gene and, thus, steroid biosynthesis. The PKA and PKC signaling pathways can directly or indirectly activate transcription factors, and both of these pathways are involved in the MAPK mediated regulation of steroidogenesis. Furthermore, cAMP and/or different factors are also capable of activating a cascade of protein kinases (Rap/Ras/Raf or other related oncoproteins) leading to a number of MAPK signaling cascades, which have been demonstrated to play important roles in regulating StAR expression and steroid biosynthesis in steroidogenic tissues.