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Articles

Luman/CREB3 Recruitment Factor Regulates Glucocorticoid Receptor Activity and Is Essential for Prolactin-Mediated Maternal Instinct

Amanda C. Martyn, Elena Choleris, Daniel J. Gillis, John N. Armstrong, Talya R. Amor, Adam R. R. McCluggage, Patricia V. Turner, Genqing Liang, Kimberly Cai, Ray Lu
Amanda C. Martyn
aDepartments of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada
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Elena Choleris
bPsychology, University of Guelph, Guelph, Ontario, Canada
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Daniel J. Gillis
cMathematics and Statistics, University of Guelph, Guelph, Ontario, Canada
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John N. Armstrong
aDepartments of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada
dBiomedical Sciences, University of Guelph, Guelph, Ontario, Canada
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Talya R. Amor
aDepartments of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada
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Adam R. R. McCluggage
aDepartments of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada
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Patricia V. Turner
ePathobiology, University of Guelph, Guelph, Ontario, Canada
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Genqing Liang
aDepartments of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada
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Kimberly Cai
aDepartments of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada
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Ray Lu
aDepartments of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada
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DOI: 10.1128/MCB.01142-12
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ABSTRACT

The hypothalamic-pituitary-adrenal (HPA) axis is a major part of the neuroendocrine system in animal responses to stress. It is known that the HPA axis is attenuated at parturition to prevent detrimental effects of glucocorticoid secretion including inhibition of lactation and maternal responsiveness. Luman/CREB3 recruitment factor (LRF) was identified as a negative regulator of CREB3 which is involved in the endoplasmic reticulum stress response. Here, we report a LRF gene knockout mouse line that has a severe maternal behavioral defect. LRF−/− females lacked the instinct to tend pups; 80% of their litters died within 24 h, while most pups survived if cross-fostered. Prolactin levels were significantly repressed in lactating LRF−/− dams, with glucocorticoid receptor (GR) signaling markedly augmented. In cell culture, LRF repressed transcriptional activity of GR and promoted its protein degradation. LRF was found to colocalize with the known GR repressor, RIP140/NRIP1, which inhibits the activity by GR within specific nuclear punctates that are similar to LRF nuclear bodies. Furthermore, administration of prolactin or the GR antagonist RU486 restored maternal responses in mutant females. We thus postulate that LRF plays a critical role in the attenuation of the HPA axis through repression of glucocorticoid stress signaling during parturition and the postpartum period.

FOOTNOTES

    • Received 20 August 2012.
    • Returned for modification 30 September 2012.
    • Accepted 8 October 2012.
    • Accepted manuscript posted online 15 October 2012.
  • Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.01142-12.

  • Copyright © 2012, American Society for Microbiology. All Rights Reserved.
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Luman/CREB3 Recruitment Factor Regulates Glucocorticoid Receptor Activity and Is Essential for Prolactin-Mediated Maternal Instinct
Amanda C. Martyn, Elena Choleris, Daniel J. Gillis, John N. Armstrong, Talya R. Amor, Adam R. R. McCluggage, Patricia V. Turner, Genqing Liang, Kimberly Cai, Ray Lu
Molecular and Cellular Biology Nov 2012, 32 (24) 5140-5150; DOI: 10.1128/MCB.01142-12

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Luman/CREB3 Recruitment Factor Regulates Glucocorticoid Receptor Activity and Is Essential for Prolactin-Mediated Maternal Instinct
Amanda C. Martyn, Elena Choleris, Daniel J. Gillis, John N. Armstrong, Talya R. Amor, Adam R. R. McCluggage, Patricia V. Turner, Genqing Liang, Kimberly Cai, Ray Lu
Molecular and Cellular Biology Nov 2012, 32 (24) 5140-5150; DOI: 10.1128/MCB.01142-12
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