Biol Reprod
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

BOR - Papers in Press, published online ahead of print December 1, 2004.
Biol Reprod 2004, 10.1095/biolreprod.104.034595
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
72/4/830    most recent
biolreprod.104.034595v2
biolreprod.104.034595v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Helvering, L.M.
Right arrow Articles by Bryant, H.U.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Helvering, L.M.
Right arrow Articles by Bryant, H.U.
Agricola
Right arrow Articles by Helvering, L.M.
Right arrow Articles by Bryant, H.U.
BIOLOGY OF REPRODUCTION 72, 830–841 (2005)
DOI: 10.1095/biolreprod.104.034595
© 2005 by the Society for the Study of Reproduction, Inc.

Differential Effects of Estrogen and Raloxifene on Messenger RNA and Matrix Metalloproteinase 2 Activity in the Rat Uterus

L.M. Helvering1,, M.D. Adrian, A.G. Geiser, S.T. Estrem, T. Wei, S. Huang, P. Chen, E.R. Dow, J. N. Calley, J.A. Dodge, T.A. Grese, S.A. Jones, D.L. Halladay, R.R. Miles, J.E. Onyia, Y.L. Ma, M. Sato, and H.U. Bryant

Lilly Research Labs, Indianapolis, Indiana 46285

A detailed analysis of the differential effects of estrogen (E) compared to raloxifene (Ral), a selective estrogen receptor modulator (SERM), following estrogen receptor (ER) binding in gynecological tissues was conducted using gene microarrays, Northern blot analysis, and matrix metalloproteinase (MMP) 2 activity studies. We profiled gene expression in the uterus following acute (1 day) and prolonged daily (5 wk) treatment of E and Ral in ovariectomized rats. Estrogen regulated twice as many genes as Ral, largely those associated with catalysis and metabolism, whereas Ral induced genes associated with cell death and negative cell regulation. Follow-up studies confirmed that genes associated with matrix integrity were differentially regulated by Ral and E at various time points in uterine and vaginal tissues. Additional experiments were conducted to determine the levels of MMP2 activity in uterus explants from ovariectomized rats following 2 wk of treatment with E, Ral, or one of two additional SERMs: lasofoxifene, and levormeloxifene. Both E and lasofoxifene stimulated uterine MMP2 activity to a level twofold that of Ral, whereas levormeloxifene elevated MMP2 activity to a level 12-fold that of Ral. These data show that one of the significant differences between E and Ral signaling in the uterus is the regulation of genes and proteins associated with matrix integrity. This may be a potential key difference between the action of SERMs in the uterus of postmenopausal women.

1 Correspondence: L.M. Helvering, Musculoskeletal Research Division, Lilly Research Labs, Indianapolis, IN 46285. FAX: 317 276 1414; l.helvering{at}lilly.com






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2005 by the Society for the Study of Reproduction.