Growth Hormone Exacerbates Diabetic Renal Damage in Male but Not Female Rats

Overview

Journal Biol Sex Differ

Publisher Biomed Central

Specialties Biology
Physiology

Date 2013 Jun 29

PMID 23805912

Citations 6

Authors

Jennifer L Whitney

Christine Maric Bilkan

Kathryn Sandberg

Adam K Myers

Susan E Mulroney

Affiliations

Soon will be listed here.

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.

Citing Articles

Insight into the Molecular Mechanism of Diabetic Kidney Disease and the Role of Metformin in Its Pathogenesis.

Kleibert M, Zygmunciak P, Lakomska K, Mila K, Zgliczynski W, Mrozikiewicz-Rakowska B Int J Mol Sci. 2023; 24(17).

PMID: 37685845 PMC: 10487922. DOI: 10.3390/ijms241713038.

Growth hormone induces mitotic catastrophe of glomerular podocytes and contributes to proteinuria.

Nishad R, Mukhi D, Singh A, Motrapu M, Chintala K, Tammineni P Cell Death Dis. 2021; 12(4):342.

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Growth hormone induces Notch1 signaling in podocytes and contributes to proteinuria in diabetic nephropathy.

Nishad R, Mukhi D, Tahaseen S, Mungamuri S, Pasupulati A J Biol Chem. 2019; 294(44):16109-16122.

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Endocytosis of Albumin Induces Matrix Metalloproteinase-9 by Activating the ERK Signaling Pathway in Renal Tubule Epithelial Cells.

Chen X, Cobbs A, George J, Chima A, Tuyishime F, Zhao X Int J Mol Sci. 2017; 18(8).

PMID: 28805677 PMC: 5578147. DOI: 10.3390/ijms18081758.

Novel Actions of Growth Hormone in Podocytes: Implications for Diabetic Nephropathy.

Mukhi D, Nishad R, Menon R, Pasupulati A Front Med (Lausanne). 2017; 4:102.

PMID: 28748185 PMC: 5506074. DOI: 10.3389/fmed.2017.00102.

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