FSH and bFGF regulate the expression of genes involved in Sertoli cell energetic metabolism

Abstract

The purpose of this study was to investigate if FSH and bFGF regulate fatty acid (FA) metabolism and mitochondrial biogenesis in Sertoli cells (SC). SC cultures obtained from 20-day-old rats were incubated with 100 ng/ml FSH or 30 ng/ml bFGF for 6, 12, 24 and 48 h. The expression of genes involved in transport and metabolism of FA such as: fatty acid transporter CD36 (FAT/CD36), carnitine-palmitoyltransferase 1(CPT1),long- and medium-chain 3-hydroxyacyl-CoA dehydrogenases (LCAD, MCAD), and of genes involved in mitochondrial biogenesis such as: nuclear respiratory factors 1 and 2 (NRF1, NRF2) and transcription factor A (Tfam), was analyzed. FSH stimulated FAT/CD36, CPT1, MCAD, NRF1, NRF2 and Tfam mRNA levels while bFGF only stimulated CPT1 expression. A possible participation of PPARb/d activation in the regulation of gene expression and lactate production was then evaluated. SC cultures were incubated with FSH or bFGF in the presence of the PPARb/d antagonist GSK3787 (GSK; 20 lM). bFGF stimulation of CPT1 expression and lactate production were inhibited by GSK. On the other hand, FSH effects were not inhibited by GSK indicating that FSH regulates the expression of genes involved in FA transport and metabolism and in mitochondrial biogenesis, independently of PPARb/d activation. FA oxidation and mitochondrial biogenesis as well as lactate production are essential for the energetic metabolism of the seminiferous tubule. The fact that these processes are regulated by hormones in a different way reflects the multifarious regulation of molecular mechanisms involved in Sertoli cell function.