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This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: 293/1/F193    most recent 00022.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Keck, M. Articles by Brooks, H. L. Search for Related Content PubMed PubMed Citation Articles by Keck, M. Articles by Brooks, H. L.

Hormonal status affects the progression of STZ-induced diabetes and diabetic renal damage in the VCD mouse model of menopause

Department of Physiology, College of Medicine, University of Arizona, Tucson, Arizona

Submitted 12 January 2007 ; accepted in final form 16 March 2007

Changes in the estrogen/testosterone balance at menopause may negatively influence the development of diabetic kidney disease. Furthermore, recent studies suggest that changes in hormone levels during perimenopause may influence disease development. Injection of 4-vinylcyclohexene diepoxide (VCD) in B₆C₃F₁ mice induces gradual ovarian failure, preserving both the perimenopausal (peri-ovarian failure) and menopausal (post-ovarian failure) periods. To address the impact of the transition into menopause on the development of diabetes and diabetic kidney damage, we used streptozotocin (STZ)-induced diabetes in the VCD model of menopause. After 6 wk of STZ-induced diabetes, blood glucose was significantly increased in post-ovarian failure (post-OF) diabetic mice compared with cycling diabetic mice. In peri-ovarian failure (peri-OF) diabetic mice, blood glucose levels trended higher but were not significantly different from cycling diabetic mice, suggesting a continuum of worsening blood glucose across the menopausal transition. Cell proliferation, an early marker of damage in the kidney, was increased in post-OF diabetic mice compared with cycling diabetic mice, as measured by PCNA immunohistochemistry. In post-OF diabetic mice, mRNA abundance of early growth response-1 (Egr-1), collagen-41, and matrix metalloproteinase-9 were increased and 3-hydroxysteroid dehydrogenase 4 (3-HSD4) and transforming growth factor-₂ (TGF-₂) were decreased compared with cycling diabetic mice. In peri-OF diabetic mice, mRNA abundance of Egr-1 and 3-HSD4 were increased, and TGF-₂ was decreased compared with cycling diabetic mice. This study highlights the importance and utility of the VCD model of menopause, as it provides a physiologically relevant system for determining the impact of the menopausal transition on diabetes and diabetic kidney damage.

diabetes; 3-HSD4; perimenopause; real-time PCR; estrogen