This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cohen, R. N. Articles by Radovick, S. Search for Related Content PubMed PubMed Citation Articles by Cohen, R. N. Articles by Radovick, S. Pubmed/NCBI databases Gene GEO Profiles HomoloGene OMIM UniGene Substance via MeSH

Enhanced Repression by HESX1 as a Cause of Hypopituitarism and Septooptic Dysplasia

Section of Endocrinology (R.N.C., C.Y., A.S., M.J.), Department of Medicine, University of Chicago, Chicago, Illinois 60637; Division of Endocrinology (L.E.C., D.B.), Department of Medicine, Children’s Hospital, Boston, Massachusetts 02115; and Section of Pediatric Endocrinology (C.Y., S.R.), Department of Pediatrics, University of Chicago, Chicago, Illinois 60637

Address all correspondence and requests for reprints to: Ronald Cohen, M.D., Section of Endocrinology, Department of Medicine, 5841 South Maryland Avenue, MC 1027, Chicago, Illinois 60637. E-mail: roncohen{at}medicine.bsd.uchicago.edu.

HESX1 is a paired-like homeodomain transcription factor that functions as a repressor of PROP1-mediated gene stimulation. Mutations in HESX1 have been implicated in cases of septooptic dysplasia and congenital hypopituitarism. All mutations in HESX1 identified to date have resulted in impaired DNA binding and defective HESX1 action. We have identified a novel HESX1 mutation in genomic nucleotide position 1684 (g.1684delG), which results in a mutant protein with increased DNA binding. In turn, this mutation causes increased repression of PROP1-dependent gene activity. These data suggest that enhancement of transcriptional repression during pituitary organogenesis is a novel mechanism for the development of congenital pituitary disorders.

This work was supported by grants from the National Institutes of Health (to R.N.C., L.E.C., and S.R.) and the Genentech Foundation for Growth and Development (to L.E.C.). M.J. was the recipient of a Howard Hughes Medical Institute Summer Student Research Fellowship.

Abbreviations: CMV, Cytomegalovirus; E13, embryonic d 13; NCoR, nuclear corepressor; PRL, prolactin; SOD, septooptic dysplasia; UAS, upstream activating sequence.

This article has been cited by other articles:

				E. Sajedi, C. Gaston-Massuet, M. Signore, C. L. Andoniadou, D. Kelberman, S. Castro, H. C. Etchevers, D. Gerrelli, M. T. Dattani, and J. P. Martinez-Barbera Analysis of mouse models carrying the I26T and R160C substitutions in the transcriptional repressor HESX1 as models for septo-optic dysplasia and hypopituitarism Dis. Model. Mech., November 1, 2008; 1(4-5): 241 - 254. [Abstract] [Full Text] [PDF]

				D. Kelberman and M. T. Dattani Hypothalamic and pituitary development: novel insights into the aetiology Eur. J. Endocrinol., August 1, 2007; 157(suppl_1): S3 - S14. [Abstract] [Full Text] [PDF]

				D. E. G. McNay, J. P. Turton, D. Kelberman, K. S. Woods, R. Brauner, A. Papadimitriou, E. Keller, A. Keller, N. Haufs, H. Krude, et al. HESX1 Mutations Are an Uncommon Cause of Septooptic Dysplasia and Hypopituitarism J. Clin. Endocrinol. Metab., February 1, 2007; 92(2): 691 - 697. [Abstract] [Full Text] [PDF]

				M.-L. Sobrier, M. Maghnie, M.-P. Vie-Luton, A. Secco, N. di Iorgi, R. Lorini, and S. Amselem Novel HESX1 Mutations Associated with a Life-Threatening Neonatal Phenotype, Pituitary Aplasia, but Normally Located Posterior Pituitary and No Optic Nerve Abnormalities J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4528 - 4536. [Abstract] [Full Text] [PDF]

				K. Hashimoto, R. N. Cohen, M. Yamada, K. R. Markan, T. Monden, T. Satoh, M. Mori, and F. E. Wondisford Cross-talk between Thyroid Hormone Receptor and Liver X Receptor Regulatory Pathways Is Revealed in a Thyroid Hormone Resistance Mouse Model J. Biol. Chem., January 6, 2006; 281(1): 295 - 302. [Abstract] [Full Text] [PDF]