Regulation of glyeoprotein hormone α-subunit gene expression

Richard A. Maurer, Kyoon E. Kim, William E. Schoderbek, Mark S. Roberson, Denis J. Glenn

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

The appropriate, regulated expression of the glycoprotein hormone subunit genes is required to enable the biosynthesis of luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, and chorionic gonadotropin. We have focused our attention on mechanisms mediating regulated transcription of the common α-subunit gene. Our studies have examined both the signaling mechanisms and the DNA elements and transcription factors that are important for α-subunit expression. Our initial efforts involved characterization of DNA elements of the α-subunit gene important for basal and GnRH-stimulated expression. Clustered point mutation analysis identified two different, unrelated sequences that play a role in α-subunit transcription. When tested as multiple copies on a minimal promoter, one of these elements was sufficient to permit a response to GnRH, while the other enhanced basal expression. Therefore, we designated these DNA elements as the GnRH-response element (GnRH-RE) and the pituitary glycoprotein hormone basal element (PGBE), respectively. The GnRH-RE contains a consensus binding site for the Ets family of transcription factors. As several Ets factors have been shown to mediate transcriptional responses to the mitogen-activated protein kinase (MAPK) pathway, we investigated the possibility that GnRH effects on α-subunit transcription may involve the MAPK cascade. We found that GnRH can indeed activate MAPK and that MAPK activation is sufficient and necessary for transcriptional activation of the α-subunit gene. Efforts to further characterize proteins that interact with the PGBE led to the cloning of a LIM-homeodomain transcription factor designated LH-2. Recombinant LH-2 selectively binds to the PGBE in vitro. Transfection experiments have shown that an expression vector for LH-2 can activate the α-subunit promoter in heterologous cells. LH-2 appears to be a component of the endogenous factors that bind to the PGBE. Thus, LH-2 appears to be an excellent candidate as a factor responsible for basal expression of the α-subunit gene. Overall, these studies have contributed to identification of molecular components important for regulated expression of the glycoprotein hormone α-subunit gene.

Original languageEnglish (US)
Pages (from-to)455-485
Number of pages31
JournalRecent progress in hormone research
Volume54
StatePublished - Dec 1 1999

ASJC Scopus subject areas

  • Endocrinology

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    Maurer, R. A., Kim, K. E., Schoderbek, W. E., Roberson, M. S., & Glenn, D. J. (1999). Regulation of glyeoprotein hormone α-subunit gene expression. Recent progress in hormone research, 54, 455-485.