Journal article
MicroRNAs Regulate Pituitary Development, and MicroRNA 26b Specifically Targets Lymphoid Enhancer Factor 1 (Lef-1), Which Modulates Pituitary Transcription Factor 1 (Pit-1) Expression
The Journal of biological chemistry, Vol.285(45), pp.34718-34728
11/05/2010
DOI: 10.1074/jbc.M110.126441
PMCID: PMC2966087
PMID: 20807761
Abstract
To understand the role of microRNAs (miRNAs) in pituitary development, a group of pituitary-specific miRNAs were identified, and Dicer1 was then conditionally knocked out using the Pitx2-Cre mouse, resulting in the loss of mature miRNAs in the anterior pituitary. The Pitx2-Cre/Dicer1 mutant mice demonstrate growth retardation, and the pituitaries are hypoplastic with an abnormal branching of the anterior lobe, revealing a role for microRNAs in pituitary development. Growth hormone, prolactin, and thyroid-stimulating hormone β-subunit expression were decreased in the Dicer1 mutant mouse, whereas proopiomelanocortin and luteinizing hormone β-subunit expression were normal in the mutant pituitary. Further analyses revealed decreased Pit-1 and increased Lef-1 expression in the mutant mouse pituitary, consistent with the repression of the Pit-1 promoter by Lef-1. Lef-1 directly targets and represses the Pit-1 promoter. miRNA-26b (miR-26b) was identified as targeting Lef-1 expression, and miR-26b represses Lef-1 in pituitary and non-pituitary cell lines. Furthermore, miR-26b up-regulates Pit-1 and growth hormone expression by attenuating Lef-1 expression in GH3 cells. This study demonstrates that microRNAs are critical for anterior pituitary development and that miR-26b regulates Pit-1 expression by inhibiting Lef-1 expression and may promote Pit-1 lineage differentiation during pituitary development.
Details
- Title: Subtitle
- MicroRNAs Regulate Pituitary Development, and MicroRNA 26b Specifically Targets Lymphoid Enhancer Factor 1 (Lef-1), Which Modulates Pituitary Transcription Factor 1 (Pit-1) Expression
- Creators
- Zichao Zhang - From the Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas 77030 andSergio Florez - From the Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas 77030 andArthur Gutierrez-Hartmann - University of Colorado DenverJames F. Martin - From the Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas 77030 andBrad A. Amendt - From the Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas 77030 and
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.285(45), pp.34718-34728
- DOI
- 10.1074/jbc.M110.126441
- PMID
- 20807761
- PMCID
- PMC2966087
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 11/05/2010
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Orthodontics; Anatomy and Cell Biology; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984284343302771
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