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Originally published In Press as doi:10.1074/jbc.M100751200 on November 14, 2001

J. Biol. Chem., Vol. 277, Issue 5, 3647-3657, February 1, 2002
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Altered Levels of Growth-related and Novel Gene Transcripts in Reproductive and Other Tissues of Female Mice Overexpressing Spermidine/Spermine N1-Acetyltransferase (SSAT)*

Seok Hong MinDagger , Rosalia C. M. SimmenDagger , Leena Alhonen§, Maria Halmekytö, Carl W. Porter, Juhani Jänne§, and Frank A. SimmenDagger ||

From the Dagger  Interdisciplinary Concentration in Animal Molecular and Cell Biology, Genetics Institute, and Department of Animal Sciences, University of Florida, Gainesville, Florida 32611-0910, the  Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, New York 14263, and the § A. I. Virtanen Institute for Molecular Sciences, University of Kuopio, P. O. Box 1627, FIN-70211 Kuopio, Finland

Overexpression of SSAT (polyamine catabolic enzyme) in female mice results in impaired ovarian folliculogenesis and uterine hypoplasia. To identify the molecular basis for this, the gene expression profiles in uterus and ovary and for comparison, liver and kidney, from non-transgenic (NT) and SSAT transgenic (ST) mice were compared. The mRNA abundance for lipoprotein lipase and glyceraldehyde-3-phosphate dehydrogenase was elevated in all four ST (>NT) tissues. The translation initiation factor-3 subunit 5 mRNA, and transcripts related to endogenous murine leukemia provirus (MLV-related) and murine retrovirus-related sequences (MuRRS) were decreased in ST tissues. A novel calmodulin-related mRNA was strongly induced in ST liver and kidney. SSAT overexpression was associated with increased levels of IGF-binding protein-2 (IGFBP-2) in the uterus and ovary, and a reduction in IGFBP-3 mRNA levels in the uterus. Exogenous spermidine and spermine elevated endogenous IGFBP-2 and SSAT mRNA abundance, whereas, putrescine stimulated IGFBP-2 mRNA abundance and transfected IGFBP-2 gene promoter activity in human (Hec-1-A) uterine cells. Sp1 and BTEB1 mRNAs that encode transcription factors for the IGFBP-2 gene also were induced in some ST tissues. The data suggest that SSAT and polyamines are important for the control of molecular pathways underlying reproductive tract tissue growth, phenotype, and function.


* This work was supported by National Institutes of Health Grants HD21961 (to R. C. M. S. and F. A. S.), CA76428 (to C. W. P. and J. J.), and CA-16056 (to C. W. P.) and by the Florida Agricultural Experiment Station. This is Florida Agricultural Experiment Station publication Series No. R-08404.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.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AY061807-AY061811.

|| To whom correspondence should be sent. Tel.: 352-392-5590; Fax: 352-392-5595; E-mail: simmen@dps.ufl.edu.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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