To determine the source of angiotensinogen excreted in urine, urine an
giotensinogen was measured in male and female rats during growth. Angi
otensinogen in 24-hr urine, measured by direct radioimmunoassay with a
ntibody against rat angiotensinogen, increased fourfold in males betwe
en the ages of 5 and 7 weeks, whereas no significant changes were obse
rved in females or castrated males. Plasma levels of angiotensinogen,
in contrast, showed no significant differences between these groups at
any age. Castration of adult males caused a significant reduction of
urinary angiotensinogen after 4 weeks. Consecutive s.c. administration
of 17 alpha-methyltestosterone for 3 weeks in castrated males resulte
d in a threefold increase in the urinary excretion of angiotensinogen,
as well as a twofold increase in the renal expression of angiotensino
gen messenger RNA (mRNA). Renal levels of angiotensinogen mRNA in inta
ct adult males were about threefold higher than those in females and c
astrated males, whereas there were no significant differences in hepat
ic angiotensinogen mRNA between these animals. These results suggest t
hat the sexual differences in the urinary excretion of angiotensinogen
are primarily due to the androgen-dependent dimorphic expression of a
ngiotensinogen mRNA in the kidney; thus, levels of angiotensinogen in
urine might reflect intrarenal production.