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

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 B(6)C(3)F(1) 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-4alpha1, and matrix metalloproteinase-9 were increased and 3beta-hydroxysteroid dehydrogenase 4 (3beta-HSD4) and transforming growth factor-beta(2) (TGF-beta(2)) were decreased compared with cycling diabetic mice. In peri-OF diabetic mice, mRNA abundance of Egr-1 and 3beta-HSD4 were increased, and TGF-beta(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.

• Authors: Maggie Keck, Melissa J Romero-Aleshire, Qi Cai, Patricia B Hoyer, Heddwen L Brooks
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 293 Issue 1 Pg. F193-9 (Jul 2007) ISSN: 1931-857X [Print] United States
• PMID: 17389681 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Blood Glucose
• Cyclohexenes
• Hormones
• Proliferating Cell Nuclear Antigen
• Vinyl Compounds
• 4-vinyl-1-cyclohexene dioxide
• RNA

Topics

• Animals
• Blood Glucose (metabolism)
• Cell Proliferation (drug effects)
• Cyclohexenes (pharmacology)
• Diabetes Mellitus, Experimental (pathology)
• Diabetic Nephropathies (pathology)
• Disease Progression
• Female
• Hormones (blood)
• Humans
• Immunohistochemistry
• Kidney Cortex (metabolism)
• Menopause (drug effects, physiology)
• Mice
• Mice, Inbred Strains
• Primary Ovarian Insufficiency (chemically induced, pathology)
• Proliferating Cell Nuclear Antigen (metabolism)
• RNA (biosynthesis, isolation & purification)
• Reverse Transcriptase Polymerase Chain Reaction
• Vinyl Compounds (pharmacology)
• Weight Gain (drug effects)