AJP - Endocrinology and Metabolism, Vol 269, Issue 1 E10-E17, Copyright © 1995 by American Physiological Society
Cortisol feedback in adrenalectomized adult sheep
A. McFarlane, J. Coghlan, J. Tresham and E. M. Wintour
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
These experiments tested the sensitivity of cortisol feedback on
adrenocorticotropic hormone (ACTH) secretion in adult sheep. In series I,
five bilaterally adrenalectomized (ADX) adult sheep were maintained on
"low" (125 micrograms/h) or "high" (500 micrograms/h) intravenous cortisol
replacement, and dose-response curves were obtained with
corticotropin-releasing factor (CRF) and arginine vasopressin (AVP). CRF
caused incremental increases in plasma ACTH at the low but not the high
dose of cortisol. AVP was similarly ineffective in stimulating ACTH at the
high dose of cortisol. However, in series II, where ADX animals were again
maintained on low or high cortisol infusions, a combined infusion of CRF
and AVP was able to stimulate a robust ACTH response during both steroid
replacement regimens. These studies demonstrate that the pituitary
represents a major site of steroid feedback in the sheep, with a relatively
small increase in the concentration of cortisol, within the normal
unstressed physiological range, being able to inhibit ACTH secretion in
response to exogenous CRF and AVP. However, under these conditions,
inhibition of ACTH release can be overcome by the combined action of CRF
and AVP. Further studies in series III, concerned with the nature of
glucocorticoid inhibition of AVP release, demonstrate that whereas exposure
to maximal cortisol levels (5,000 micrograms/h) completely abolishes the
ACTH response to severe hemorrhage (15 ml/kg over 15 min), AVP release is
maintained, suggesting that the system controlling AVP release during
hemorrhagic stress is less sensitive to the negative influences of
glucocorticoids than is the system controlling ACTH release.
