Journal article
Follicle-stimulating hormone/cAMP regulation of aromatase gene expression requires β-catenin
Proceedings of the National Academy of Sciences - PNAS, Vol.103(33), pp.12435-12440
08/15/2006
Handle:
https://hdl.handle.net/2376/116477
PMCID: PMC1533882
PMID: 16895991
Abstract
Estrogens profoundly influence the physiology and pathology of reproductive and other tissues. Consequently, emphasis has been placed on delineating the mechanisms underlying regulation of estrogen levels. Circulating levels of estradiol in women are controlled by follicle-stimulating hormone (FSH), which regulates transcription of the aromatase gene (
CYP19A1
) in ovarian granulosa cells. Previous studies have focused on two downstream effectors of the FSH signal, cAMP and the orphan nuclear receptor steroidogenic factor-1 (NR5A1). In this report, we present evidence for β-catenin (CTNNB1) as an essential transcriptional regulator of
CYP19A1
. FSH induction of select steroidogenic enzyme mRNAs, including
Cyp19a1
, is enhanced by β-catenin. Additionally, β-catenin is present in transcription complexes assembled on the endogenous gonad-specific
CYP19A1
promoter, as evidenced by chromatin immunoprecipitation assays. Transient expression and RNAi studies demonstrate that FSH- and cAMP-dependent regulation of this promoter is sensitive to alterations in the level of β-catenin. The stimulatory effect of β-catenin is mediated through functional interactions with steroidogenic factor-1 that involve four acidic residues within its ligand-binding domain, mutation of which attenuates FSH/cAMP-induced
Cyp19a1
mRNA accumulation. Together, these data demonstrate that β-catenin is essential for FSH/cAMP-regulated gene expression in the ovary, identifying a central and previously unappreciated role for β-catenin in estrogen biosynthesis, and a potential broader role in other aspects of follicular maturation.
Metrics
12 Record Views
Details
- Title
- Follicle-stimulating hormone/cAMP regulation of aromatase gene expression requires β-catenin
- Creators
- Tehnaz N Parakh - School of Molecular Biosciences, Washington State University, Pullman, WA 99164Jennifer A Hernandez - School of Molecular Biosciences, Washington State University, Pullman, WA 99164Jean C Grammer - School of Molecular Biosciences, Washington State University, Pullman, WA 99164Jennifer Weck - School of Molecular Biosciences, Washington State University, Pullman, WA 99164Mary Hunzicker-Dunn - School of Molecular Biosciences, Washington State University, Pullman, WA 99164Anthony J Zeleznik - Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, PA 15621John H Nilson - School of Molecular Biosciences, Washington State University, Pullman, WA 99164
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.103(33), pp.12435-12440
- Academic Unit
- Molecular Biosciences, School of
- Publisher
- National Academy of Sciences
- Identifiers
- 99900548336801842
- Language
- English
- Resource Type
- Journal article