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Taken from WWW.pubmed.gov (testosterone studies)
Am J Physiol Renal Physiol. 2007 Mar 27; [Epub ahead of print]
Hormonal status affects the progression of STZ-induced diabetes and diabetic renal
damage in the VCD mouse model of menopause.
Keck M, Romero-Aleshire MJ, Cai Q, Hoyer PB, Brooks HL.
Physiology, University of Arizona, Tucson, Arizona, United States.
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 STZ-induced diabetes in the VCD model of menopause. After six weeks of STZ-induced diabetes,
blood glucose was significantly increased in post-ovarian failure (post-OF) diabetic mice compared
to 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 to cycling diabetic
mice, as measured by PCNA immunohistochemistry. In post-OF diabetic mice mRNA abundance of early
growth response-1 (Egr-1), collagen-4alpha1 and matrix metalloproteinase-9 were increased and
3beta-hydroxysteroid dehydrogenase 4 (3beta-HSD4) and transforming growth factor-beta2 (TGFbeta2)
were decreased compared to cycling diabetic mice. In peri-OF diabetic mice mRNA abundance of Egr-1
and 3beta-HSD4 were increased, and TGFbeta2 was decreased compared to 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. Key words: Diabetes, perimenopause, 3β-HSD4, estrogen, real-time PCR.
PMID: 16749913 [PubMed - as supplied by publisher]
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