CORTISOL FEEDBACK IN ADRENALECTOMIZED ADULT SHEEP

These experiments tested the sensitivity of cortisol feedback on adren ocorticotropic hormone (ACTH) secretion in adult sheep. In series I, f ive bilaterally adrenalectomized (ADX) adult sheep were maintained on ''low'' (125 mu g/h) or ''high'' (500 mu g/h) intravenous cortisol rep lacement, and dose-response curves were obtained with corticotropin-re leasing factor (CRF) and arginine vasopressin (AVP). CRF caused increm ental increases in plasma ACTH at the low but not the high dose of cor tisol. AVP was similarly ineffective in stimulating ACTH at the high d ose of cortisol. However, in series II, where ADX animals were again m aintained on low or high cortisol infusions, a combined infusion of CR F and AVP was able to stimulate a robust ACTH response during both ste roid replacement regimens. These studies demonstrate that the pituitar y represents a major site of steroid feedback in the sheep, with a rel atively small increase in the concentration of cortisol, within the no rmal unstressed physiological range, being able to inhibit ACTH secret ion in response to exogenous CRF and AVP. However, under these conditi ons, inhibition of ACTH release can be overcome by the combined action of CRF and AVP. Further studies in series III, concerned with the nat ure of glucocorticoid inhibition of AVP release, demonstrate that wher eas exposure to maximal cortisol levels (5,000 mu g/h) completely abol ishes the ACTH response to severe hemorrhage (15 ml/kg over 15 min), A VP release is maintained, suggesting that the system controlling AVP r elease during hemorrhagic stress is less sensitive to the negative inf luences of glucocorticoids than is the system controlling ACTH release .