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Bip Is a Molecular Link between the Phase I and Phase II Estrogenic Responses in Uterus

Division of Reproductive and Developmental Biology, Departments of Pediatrics and Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232

Address all correspondence and requests for reprints to: Sanjoy K. Das, Ph.D., Division of Reproductive and Developmental Biology, Department of Pediatrics, D-4105 Medical Center North, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, Tennessee 37232-2678. E-mail: sanjoy.das{at}vanderbilt.edu.

Uterine estrogenic actions are biphasic, early (phase I) and late (phase II) responses. However, the molecular linkage between these phases is not known. Although certain phase I responses are considered estrogen receptor (ER) and ERß independent, the phase II responses are ER dependent. We previously observed that among several genes Bip is induced by estrogen in the mouse uterus in an ER-independent manner as a phase I response. Bip is a member of the chaperone family and plays roles in protein processing and confers cellular protection. However, its role in estrogen-dependent uterine biology is unknown. We show here a new function of Bip in regulating estrogen signaling in the uterus. Bip, induced during the phase I responses, molecularly interacts with ER required for estrogen-mediated phase II growth responses. Utilizing in vivo and in vitro model systems, we found that adenovirus-driven suppression of Bip antagonizes ER-mediated uterine gene transcription. Importantly, down-regulation of Bip compromises estrogen-dependent phase II growth responses with sustained phase I responses. In conclusion, Bip is critical for coordinating estrogen-elicited biphasic responses and serves as a molecular link between ER-independent and -dependent estrogenic responses in the uterus.

NURSA Molecule Pages Link:

Nuclear Receptors:   ERα

Ligands:   17β-Estradiol

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