Ka. Scribner et al., STREPTOZOTOCIN-DIABETIC RATS EXHIBIT FACILITATED ADRENOCORTICOTROPIN RESPONSES TO ACUTE STRESS, BUT NORMAL SENSITIVITY TO FEEDBACK BY CORTICOSTEROIDS, Endocrinology, 133(6), 1993, pp. 2667-2674
A variety of chronic stress paradigms have been shown to increase basa
l activity in the hypothalamic-pituitary-adrenocortical axis, resultin
g in hypercorticoidism. Despite this, chronically stressed rats typica
lly exhibit facilitated ACTH responses to acute novel stress, suggesti
ng that the activity of some central neural component(s) in the axis i
s facilitated by chronic stress. We have used the chronic stress of st
reptozotocin (STZ)-induced diabetes in rats to determine diurnal sensi
tivity of basal and stimulated ACTH secretion to exogenous corticoster
one (B) feedback in vivo. Control and STZ-diabetic rats were adrenalec
tomized or adrenalectomized and implanted with a 30% or 50% B pellet a
t the time of vehicle/STZ injection. Rats were killed 5 days later, un
der basal conditions or after 6 min of restraint, in the morning or ev
ening. We show that basal ACTH secretion in both the morning and eveni
ng was similarly suppressed by B in STZ-diabetic and control rats. How
ever, stress-induced ACTH secretion was significantly greater in STZ-d
iabetic compared to control rats throughout the range 3-7 mug/dl B, wh
en tested in the morning. Suppression of evening stress-induced ACTH s
ecretion by B was also significantly different in STZ-diabetic rats; h
owever, the IC50 values for the inhibition of ACTH by B did not differ
. This result shows that in the evening after stress and under basal c
onditions in both the morning and evening, sensitivity to B feedback i
s normal in chronically stressed, STZ-diabetic rats. Despite the obser
ved facilitation of morning stress-induced ACTH secretion in STZ-diabe
tic rats, there were no differences in hypothalamic CRF content betwee
n control and STZ-diabetic tissue. We conclude that 1) the facilitator
y input to the paraventricular nucleus functions primarily at the time
of the circadian trough to maintain or enhance acute stress responsiv
eness in chronically stressed, hypercorticoid rats; and 2) the sensiti
vity of ACTH to inhibition by B is normal in rats chronically stressed
by STZ-induced diabetes.