Levels of urinary inter-α-trypsin inhibitor trimer as a function of age and sex-hormone status in males and females not forming stones

Abstract

To determine if levels of inter-alpha-trypsin inhibitor (I alpha TI)-trimer differ in normal individuals based on age, gender or hormonal status, as the regulation of calcium oxalate (CaOx) crystallization inhibitors, e.g. by sex steroids, could be a mechanism contributing to the differences in CaOx urolithiasis between the sexes. Voided urine samples were collected from normal males and females. In Experiment 1 samples were grouped by gender and age, i.e. paediatric (PED) < or = 10 years, male (M) 21, female (F) 14; young adult (YGAD) 20-30 years, M 23, F 18; adults (AD), 35-50 year, M 25, F 13; adults aged > or = 60 years (> 60), M 24, F 16 (totals, M 93, F 61). In Experiment 2 samples were grouped by gender, age and hormonal status, i.e. PED, M 24, F 17; AD, M 24, F 22; > 60 and not on hormonal therapy, M 23, F 30; M > 60 and on androgen deprivation therapy (ANDEP) 18; and F > 60 on oestrogen supplementation, F+EST, 18 (total M 89, F 85). Levels of urinary I alpha TI-trimer were determined by immunoblotting and enhanced chemiluminescence, and relative densities of the bands determined. In both experiments the relative levels of I alpha TI-trimer were 2-7 times higher in M-PED than in all other groups of males (P < or = 0.007). Among adult males, I alpha TI-trimer levels were similar in all groups, including ANDEP (P > or = 0.9). There were no differences in the relative levels of I alpha TI-trimer among any of the groups of females, regardless of age or hormonal status (P > or = 0.7). In males a decrease in I alpha TI-trimer was associated with the onset of adulthood and entry into the 'stone-forming years'. Females did not show this decrease, and neither sex showed an increase in I alpha TI-trimer in the > 60 group, when the incidence of CaOx urolithiasis is supposedly declining. While changes in urinary I alpha TI-trimer levels in males may reflect maturational changes in the kidney, overall these data do not support the hypothesis that the age-related changes in the incidence of urolithiasis are paralleled by changes in the expression I alpha TI-trimer. Additionally, the sex steroids do not appear to acutely regulate the expression of I alpha TI-trimer in adults, making differences in I alpha TI-trimer levels unlikely to be the reason for the disparity in the incidence of CaOx urolithiasis between the sexes.