Effects of TG interaction factor 1 on synthesis of estradiol and progesterone in granulosa cells of goats through SMAD2/3-SP1 signaling pathway.

The TG interaction factor 1 (TGIF1) is of the TALE homologue domain protein family and is considered as a transcriptional repressor of SMAD protein that interacts with DNA through a specific consensus-binding site for TG and recruits mSin3A and histone deacetylases to the SMAD complex. In this study, there is the first detailed description of TGIF1 on steroidogenesis in goat granulosa cells. When there is a relatively greater expression of the TGIF1 gene, there is a lesser abundance of CYP11A1, CYP19A1, and StAR mRNA transcript and protein and 3β-HSD mRNA transcript in granulosa cells of goats. Furthermore, there were lesser concentrations of 17β-estradiol (E) and progesterone (P) in culture medium when there was greater TGIF1 gene expression and there were greater concentrations of these hormones in the culture medium when there was lesser TGIF1 gene expression. There may be functions of TGIF1, therefore, in suppression of SMAD-induced E and P production and in decreasing the phosphorylation of SMAD2/3 in granulosa cells of goats and relative abundance of the SMAD2/3 protein transcription factor, SP1. With suppression of TGIF1 gene expression, there was a reversal of SP1-induced suppression of steroidogenesis-related genes. Results of the present study provide insights about the potential mechanism underlying the regulation of granulosa cell steroidogenesis of goats by TGIF1.