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Open Access Research

Growth hormone exacerbates diabetic renal damage in male but not female rats

Jennifer L Whitney1, Christine Maric Bilkan2, Kathryn Sandberg134, Adam K Myers14 and Susan E Mulroney14*

Author Affiliations

1 Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20057-1640, USA

2 Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA

3 Department of Medicine, Georgetown University Medical Center, Washington, DC, USA

4 Center for the Study of Sex Differences in Health, Aging and Disease, Georgetown University Medical Center, Washington, DC, USA

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Biology of Sex Differences 2013, 4:12  doi:10.1186/2042-6410-4-12

Published: 27 June 2013

Abstract

Background

Human and animal studies support the idea that there are sex differences in the development of diabetic renal disease. Our lab and others have determined that in addition to Ang II (through the AT1R), growth hormone (GH) contributes to renal damage in models of renal failure; however, the impact of sex and GH on the mechanisms initiating diabetic renal disease is not known. This study examined the effect of sex and GH on parameters of renal damage in early, uncontrolled streptozotocin (STZ)-induced diabetes.

Methods

Adult male and female Sprague–Dawley rats were injected with vehicle (control), STZ, or STZ + GH and euthanized after 8 weeks.

Results

Mild but significant glomerulosclerosis (GS) and tubulointerstitial fibrosis (TIF) was observed in both kidneys from male and female diabetic rats, with GH significantly increasing GS and TIF by 30% and 25% in male rats, but not in female rats. STZ increased TGF-β expression in both kidneys from male and female rats; however, while GH had no further effect on TGF-β protein in diabetic females, GH increased TGF-β protein in the male rat’s kidneys by an additional 30%. This sex-specific increase in renal injury following GH treatment was marked by increased MCP-1 and CD-68+ cell density. STZ also reduced renal MMP-2 and MMP-9 protein expression in both kidneys from male and female rats, but additional decreases were only observed in GH-treated diabetic male rats. The sex differences were independent of AT1R activity.

Conclusions

These studies indicate that GH affects renal injury in diabetes in a sex-specific manner and is associated with an increase in pro-inflammatory mediators.

Keywords:
Sex Differences; Gender; Glomerulosclerosis; Renal Injury; TGF-β; Inflammation