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

Maggie Keck, Melissa J. Romero-Aleshire, Qi Cai, Patricia B. Hoyer, Heddwen L. Brooks

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

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-4α1, and matrix metalloproteinase-9 were increased and 3β-hydroxysteroid dehydrogenase 4 (3β-HSD4) and transforming growth factor-β2 (TGF-β2) were decreased compared with cycling diabetic mice. In peri-OF diabetic mice, mRNA abundance of Egr-1 and 3β-HSD4 were increased, and TGF-β2 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.

Original languageEnglish (US)
Pages (from-to)F193-F199
JournalAmerican Journal of Physiology - Renal Physiology
Volume293
Issue number1
DOIs
StatePublished - Jul 1 2007

Keywords

  • 3β-HSD4
  • Diabetes
  • Estrogen
  • Perimenopause
  • Real-time PCR

ASJC Scopus subject areas

  • Physiology
  • Urology

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