Sex Differences in Protein Excretion in Mice Consuming High Protein Diet: Effect of sex steroids on renal protein excretion in mice

Background: Normally, the renal excretion of protein (or proteinuria) is absent or very small. Ingesting high-protein diets can elevate proteinuria and in the long term, increase the work on the kidney by increasing glomerular filtration and higher energy requirement to handle the protein. Sex differences in renal function are well known and thus, differences in proteinuria may exist. The purpose of this study was to determine if sex differences exist in proteinuria in mice consuming high protein diet and investigate the potential roles of the sex steroids 17beta-estrogen (E2) and testosterone.

Methods: Healthy 3-4-week-old male and female intact and gonadectomized mice were used. Mice were placed in individual metabolic cages where the urine of each mouse could be collected and measured for protein concentration. Mice consumed a 40% casein protein diet for 25 days (normal protein = 20% protein). Some gonadectomized female mice received exogenous E2 and gonadectomized male mice received exogenous testosterone. Proteinuria was measured via dipstick measurement and protein excretion (mg/day) i.e., urine flow rate (ml/day) x urine protein concentration(mg/day).

Results: Intact male mice had significantly higher proteinuria compared to intact female mice (5-10 mg/day vs 25-30 mg/day, p<0.001). Gonadectomized male and female mice had very low proteinuria (3- 5 mg/day). Gonadectomized testosterone-treated male mice had high proteinuria not different from the intact male mice. Gonadectomized E2-treated female mice had similar proteinuria compared to intact female mice and slightly though not significantly higher than gonadectomized placebo-treated female mice.

Conclusion: The results of this study suggest that the male sex steroid induces high proteinuria in mice consuming high protein levels. The female sex steroid plays no role or only a minor role in proteinuria under these experimental conditions. Our results suggest that androgens may account for the higher incidence of kidney disease in males compared to age-matched pre-menopausal females.