This study examined the physiological effect of reduced plasma cortiso
l (C) during prolonged exercise in humans. The effects of normal C (NC
) were compared with metyrapone-induced low C (LC) on plasma substrate
availability and the respiratory exchange ratio during 2 h of exercis
e at similar to 60% peak O-2 consumption in nine subjects. The C respo
nses were compared with preexercise (Pre) levels and with a rest day (
Con). At rest, C was attenuated by similar to 70% for LC compared with
NC. At rest, plasma glucose, lactate, glycerol, beta-hydroxybutyrate,
alanine, branched-chain amino acids, insulin, glucagon, growth hormon
e, epinephrine, and norepinephrine were similar under LC and NC (P > 0
.05). During exercise under NC, plasma C increased compared with Pre,
whereas it remained unchanged during LC. During NC, plasma C was eleva
ted at 90 min (compared with Con) and at 120 min (compared with Con an
d Pre). During exercise, plasma glucose decreased to the same extent a
nd lactate was similar under both conditions, whereas plasma glycerol,
beta-hydroxybutyrate, alanine, and branched-chain amino acids were hi
gher (P < 0.01) under NC. Plasma insulin declined (P = 0.01) to a grea
ter extent under LC, whereas growth hormone, epinephrine, and norepine
phrine tended to be higher (0.05 less than or equal to P less than or
equal to 0.10). Plasma glucagon increased under both conditions (P < 0
.01). The respiratory exchange ratio did not differ between conditions
. We conclude that, during exercise, 1) C accelerates lipolysis, ketog
enesis, and proteolysis; 2) under LC, glucoregulatory hormone adjustme
nts maintain glucose homeostasis; and 3) LC does not alter whole body
substrate utilization or the ability to complete 2 h of moderate exerc
ise.