Insulin enhances the transcription of luteinizing hormone-beta gene.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Insulin enhances the transcription of LHbeta gene. This modulation may contribute to the pathophysiology of polycystic ovary syndrome.
Department of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, MO, USA.
Christoph
C
Dorn
Jean-François
JF
Mouillet
Xiaomei
X
Yan
Qinglin
Q
Ou
Yoel
Y
Sadovsky
D000818:Animals; D002460:Cell Line; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D051717:Fushi Tarazu Transcription Factors; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection
C400152:DNA enzyme ED5; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D007328:Insulin; D037101:Luteinizing Hormone, beta Subunit; D014157:Transcription Factors