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

Inhibin α 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 α-subunit promoter activity. The inhibin α 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 α-subunit transcription. Both GATA4 and GATA6 strongly synergized with LRH-1. Consistent with the cAMP-dependence of the inhibin α-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 α-subunit gene expression.