Insulin enhances the transcription of luteinizing hormone-beta gene.

Abstract

Hyperinsulinemia and insulin resistance are implicated in the pathophysiology of polycystic ovary syndrome, a condition associated with elevated levels of LH. We tested the hypothesis that insulin enhances the transcriptional activity of LHbeta promoter. We transfected the gonadotrope cell line LbetaT2 with a plasmid that expresses the proximal promoter of LHbeta gene upstream of luciferase, and determined insulin effect on endogenous LHbeta mRNA. We found that insulin stimulated (2-4 fold) the activity of this promoter in a time- and concentration-dependent manner. Accordingly, insulin up-regulated the level of LHbeta mRNA. In contrast, insulin had no significant effect on GnRH-dependent LHbeta expression. The expression of Egr-1 and SF-1, which are essential for transcription of LHbeta gene, was unchanged by insulin. Insulin enhances the transcription of LHbeta gene. This modulation may contribute to the pathophysiology of polycystic ovary syndrome.