Cortisol feedback in adrenalectomised adult sheep.
McFarlane, Andrew, John Coghlan, Janette Tresham, and E. Marelyn
Wintour.
Howard Florey Institute of Experimental Physiology and Medicine,
University of Melbourne, Parkville, Victoria, Australia, 3052.
APStracts 2:0024E, 1995.
These experiments tested the sensitivity of cortisol feedback on ACTH
secretion in adult sheep. Series I - Five bilaterally
adrenalectomised (ADX) adult sheep were maintained on either `low'
(125 [mu]g/h) or `high' (500 [mu]g/h) intravenous cortisol replacement and
dose-response curves obtained with 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 a second
series of experiments (Series II), where ADX animals were again
maintained on `low' or `high' cortisol infusions, a combined infusion
of both CRF and AVP was able to stimulate a robust ACTH response
during both steroid replacement regimes. 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 both CRF and AVP. Further studies
(Series III), concerned with the nature of glucocorticoid inhibition
of AVP release, demonstrate that while exposure to maximal cortisol
levels (5000 [mu]g/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.
Received 21 November 1994; accepted in final form 2 February
1995.
APS Manuscript Number E462-4.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 February 1995.