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Originally published In Press as doi:10.1074/jbc.M003827200 on July 11, 2000
J. Biol. Chem., Vol. 275, Issue 37, 28834-28842, September 15, 2000
Estrogen Targets Genes Involved in Protein Processing, Calcium
Homeostasis, and Wnt Signaling in the Mouse Uterus Independent of
Estrogen Receptor- and - *
Sanjoy K.
Das §¶,
Jian
Tan ,
Shefali
Raja ,
Jyotsnabaran
Halder§,
Bibhash C.
Paria§ , and
Sudhansu K.
Dey§
From the Department of Obstetrics & Gynecology, the
§ Department of Molecular & Integrative Physiology, and
the Department of Pediatrics, Ralph L. Smith Research Center,
University of Kansas Medical Center, Kansas City, Kansas 66160
Estrogen actions in target organs are normally
mediated via activation of nuclear estrogen receptors (ERs). By using
mRNA differential display technique, we show, herein, that
estradiol-17 (E2) and its catechol metabolite
4-hydroxy-E2 (4OHE2) can modulate uterine gene
expression in ER ( / ) mice. Whereas administration of
E2 or 4OHE2 rapidly up-regulated (4-8-fold)
the expression of immunoglobulin heavy chain binding protein
(Bip), calpactin I (CalP),
calmodulin (CalM), and Sik similar protein
(Sik-SP) genes in ovariectomized wild-type or ER ( / )
mice, the expression of secreted frizzled related protein-2
(SFRP-2) gene was down-regulated (4-fold). Bip, CalP, and
CalM are calcium-binding proteins and implicated in calcium
homeostasis, whereas SFRP-2 is a negative regulator of Wnt signaling.
Bip and Sik-SP also possess chaperone-like functions. Administration of
ICI-182,780 or cycloheximide failed to influence these estrogenic
responses, demonstrating that these effects occur independent of ER ,
ER , or protein synthesis. In situ hybridization showed
differential cell-specific expression of these genes in wild-type and
ER ( / ) uteri. Although progesterone can antagonize or synergize
estrogen actions, it had minimal effects on these estrogenic responses.
Collectively, the results demonstrate that estrogens have a unique
ability to influence specific genes in the uterus not involving
classical nuclear ERs.
*
This work was supported in part by National Institutes of
Health Grants ES-07814 (to S. K. Das), HD-12304, and HD-29968 (to S. K. Dey).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
¶
To whom correspondence should be addressed: Dept. of
Obstetrics & Gynecology, MRRC 37/3004, University of Kansas Medical
Center, 3901 Rainbow Blvd., Kansas City, KS 66160-7338. Tel.:
913-588-7379; Fax: 913-588-5677; E-mail: sdas@kumc.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.
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