SEX DIFFERENCES AND THE ROLES OF ESTROGEN AND TESTOSTERONE IN RENAL PROTEIN EXCRETION IN MICE CONSUMING A HIGH PROTEIN DIET: Sex Steroids and Protein Excretion

Background:  Sex differences in renal function are well known and thus, differences in urinary protein excretion or proteinuria may exist.  The purpose of this study was to determine if sex differences in proteinuria occur in mice consuming a high protein (HP) diet and to investigate the potential roles of the sex steroids estrogen (E2) and testosterone (T). 

Methods:  Healthy 5-week-old male and female intact and gonadectomized mice were placed in metabolic cages.  Mice consumed a HP diet of 40% casein (normal = 20%) for 25 days.  Some gonadectomized female and male mice received exogenous E2 and T, respectively.  Renal protein excretion (PE) was determined by measuring total protein excretion (mg/day) (i.e., urine flow rate (ml/day) x urine protein concentration (mg/day)). 

Results:  Intact male mice had significantly higher PE 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 PE (3-5 mg/day).  Gonadectomized E2-treated female mice had similar PE compared to intact female mice and slightly though not significantly higher than gonadectomized placebo-treated female mice.  Gonadectomized, T-treated male mice had high PE not different from the intact male mice. 

Conclusions:  Testosterone induces high proteinuria in mice consuming high protein whereas E2 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, premenopausal females.