LRH-1/NR5A2 cooperates with GATA factors to regulate inhibin alpha-subunit promoter activity

Inhibin alpha is the common subunit of the dimeric inhibin proteins known for their role in suppressing pituitary FSH secretion. In this study, we have examined the role of GATA factors and the nuclear receptor, LRH-1/NR5A2, in the regulation of inhibin alpha-subunit promoter activity. The inhibin alpha promoter contains two GATA-binding motifs that can be activated by GATA4 or GATA6. The GATA-dependence of the promoter was demonstrated by downregulating GATA expression in MA-10 cells using siRNA technology. We next examined whether GATA factors could cooperate with LRH-1, a factor recently proposed to be an important regulator of inhibin alpha-subunit transcription. Both GATA4 and GATA6 strongly synergized with LRH-1. Consistent with the cAMP-dependence of the inhibin alpha-subunit promoter, GATA/LRH-1 synergism was markedly enhanced by PKA and the co-activator protein CBP. Thus, our results identify LRH-1 as a new transcriptional partner for GATA factors in the regulation of inhibin alpha-subunit gene expression.