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Dev Cell. 2014 May 27;29(4):482-90. doi: 10.1016/j.devcel.2014.04.016.

Membrane-localized estrogen receptor α is required for normal organ development and function.

Author information

1
Division of Endocrinology, Department of Medicine, University of California, Irvine, Irvine, CA 92717, USA.
2
Department of Veterans Affairs Medical Center, Long Beach, Long Beach, CA 90822, USA.
3
Department of Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
4
Department of Medicine, University of Rochester, Rochester, NY 14642, USA.
5
Division of Endocrinology, Department of Medicine, University of California, Irvine, Irvine, CA 92717, USA; Department of Veterans Affairs Medical Center, Long Beach, Long Beach, CA 90822, USA. Electronic address: ellis.levin@va.gov.

Abstract

Steroid receptors are found in discrete cellular locations, but it is unknown whether extranuclear pools are necessary for normal organ development. To assess this, we developed a point mutant estrogen receptor α (ERα) knockin mouse (C451A) that precludes palmitoylation and membrane trafficking of the steroid receptor in all organs. Homozygous knockin female mice (nuclear-only ERα [NOER]) show loss of rapid signaling that occurs from membrane ERα in wild-type mice. Multiple developmental abnormalities were found, including infertility, relatively hypoplastic uteri, abnormal ovaries, stunted mammary gland ductal development, and abnormal pituitary hormone regulation in NOER mice. These abnormalities were rescued in heterozygous NOER mice that were comparable to wild-type mice. mRNAs implicated in organ development were often poorly stimulated by estrogen only in homozygous NOER mice. We conclude that many organs require membrane ERα and resulting signal transduction to collaborate with nuclear ERα for normal development and function.

PMID:
24871949
PMCID:
PMC4062189
DOI:
10.1016/j.devcel.2014.04.016
[Indexed for MEDLINE]
Free PMC Article

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