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Mol. Hum. Reprod. Advance Access published online on November 29, 2007
Molecular Human Reproduction, doi:10.1093/molehr/gam080
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

hormone control and expression of androgen receptor coregulator mage-11 in human endometrium during the window of receptivity to embryo implantation

Suxia Bai1,2, Gail Grossman1,3, Lingwen Yuan1,4, Bruce A. Lessey1,6, Frank S. French1,2, Steven L. Young1,4 and Elizabeth M. Wilson1,2,5,

1Laboratories for Reproductive Biology 2Department of Pediatrics, University of North Carolina, Chapel Hill, NC 27599 USA 3Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, NC 27599 USA 4Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, NC 27599 USA 5Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599 USA 6Division of Reproductive Endocrinology and Infertility, University Medical Group, Department of Obstetrics and Gynecology, Greenville Hospital System, Greenville, SC 29605 USA

Address correspondence to Elizabeth M. Wilson, Laboratories for Reproductive Biology, CB#7500, University of North Carolina, Chapel Hill NC 27599-7500 USA TEL 919-966-5168, FAX 919-966-2203, emw{at}med.unc.edu

The androgen receptor (AR) is a ligand activated transcription factor of the male and female reproductive tracts whose activity is modulated by coregulator binding. We recently identified melanoma antigen gene protein-11 (MAGE-11) of the MAGEA gene family that functions as an AR coregulator by binding the AR NH2-terminal FXXLF motif. Here we report that MAGE-11 is expressed in a temporal fashion in endometrium of normally cycling women. Highest levels of MAGE-11 mRNA and protein occur in the mid-secretory stage, coincident with the window of uterine receptivity to embryo implantation. Studies in human endometrial cell lines together with the hormone profile of the menstrual cycle and pattern of estrogen receptor-{alpha} expression in cycling endometrium suggest the rise in MAGE-11 mRNA results from down-regulation by estradiol during the proliferative phase and up-regulation by cyclic AMP signalling in the early and mid-secretory stage. In agreement with its coregulatory function, MAGE-11 localizes with AR in glandular epithelial cell nuclei in the mid-secretory stage. The increase in AR protein in the mid-secretory endometrium without an increase in AR mRNA suggests MAGE-11 stabilizes AR in glandular epithelial cell nuclei. This was supported by expression studies at low androgen levels indicating AR stabilization by MAGE-11 dependent on the AR NH2-terminal transactivation domain. The results suggest that MAGE-11 functions as a coregulator that increases AR transcriptional activity during the establishment of uterine receptivity in the human female.

Key Words: androgen receptor/human endometrium/melanoma antigen gene protein 11 (MAGE-11)/estrogen receptor/cyclic AMP

Submitted on August 9, 2007; resubmitted on November 6, 2007; accepted on November 26, 2007.


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