Streptozotocin-diabetic rats exhibit facilitated adrenocorticotropin responses to acute stress, but normal sensitivity to feedback by corticosteroids

Endocrinology. 1993 Dec;133(6):2667-74. doi: 10.1210/endo.133.6.8243290.


A variety of chronic stress paradigms have been shown to increase basal activity in the hypothalamic-pituitary-adrenocortical axis, resulting in hypercorticoidism. Despite this, chronically stressed rats typically exhibit facilitated ACTH responses to acute novel stress, suggesting that the activity of some central neural component(s) in the axis is facilitated by chronic stress. We have used the chronic stress of streptozotocin (STZ)-induced diabetes in rats to determine diurnal sensitivity of basal and stimulated ACTH secretion to exogenous corticosterone (B) feedback in vivo. Control and STZ-diabetic rats were adrenalectomized or adrenalectomized and implanted with a 30% or 50% B pellet at the time of vehicle/STZ injection. Rats were killed 5 days later, under basal conditions or after 6 min of restraint, in the morning or evening. We show that basal ACTH secretion in both the morning and evening was similarly suppressed by B in STZ-diabetic and control rats. However, stress-induced ACTH secretion was significantly greater in STZ-diabetic compared to control rats throughout the range 3-7 micrograms/dl B, when tested in the morning. Suppression of evening stress-induced ACTH secretion by B was also significantly different in STZ-diabetic rats; however, 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 conditions in both the morning and evening, sensitivity to B feedback is normal in chronically stressed, STZ-diabetic rats. Despite the observed facilitation of morning stress-induced ACTH secretion in STZ-diabetic rats, there were no differences in hypothalamic CRF content between control and STZ-diabetic tissue. We conclude that 1) the facilitatory input to the paraventricular nucleus functions primarily at the time of the circadian trough to maintain or enhance acute stress responsiveness in chronically stressed, hypercorticoid rats; and 2) the sensitivity of ACTH to inhibition by B is normal in rats chronically stressed by STZ-induced diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adrenalectomy
  • Adrenocorticotropic Hormone / blood*
  • Animals
  • Blood Glucose / analysis
  • Corticosterone / blood*
  • Corticotropin-Releasing Hormone / blood
  • Diabetes Mellitus, Experimental / metabolism*
  • Feedback
  • Male
  • Pituitary Gland / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reference Values
  • Stress, Physiological / blood*
  • Stress, Physiological / metabolism


  • Blood Glucose
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Corticosterone