Altered levels of growth-related and novel gene transcripts in reproductive and other tissues of female mice overexpressing spermidine/spermine N1-acetyltransferase (SSAT)

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.