EVIDENCE FOR THE INTERNAL FEEDBACK PHENOMENON IN HUMAN SUBJECTS: EFFECTS OF ACTH ON PLASMA CRF

Abstract

ABSTRACT Corticotrophin (ACTH) was administered to three patients with lipoatrophic diabetes (LD), one hypophysectomized LD patient and one control subject in an effort to simulate the internal feedback mechanism as measured by plasma corticotrophin releasing factor (CRF) activity. Plasma cortisol was determined at zero, five and eight hours after the beginning of ACTH infusion. Every LD patient showed a lack of adrenal response to ACTH as evidenced by the absence of significant increments in plasma cortisol levels. The control subject had a normal adrenal response to ACTH. Three of the four LD patients showed a reduction in plasma CRF levels after ACTH. The control subject had no detectable plasma CRF before or after ACTH. The reduction in plasma CRF accompanied by constant levels of plasma cortisol after ACTH administration suggests a direct regulatory effect of ACTH on CRF secretion. These data provide strong supportive evidence for the existence of an internal or 'short-loop' feedback system in human subjects in which the levels of plasma CRF appear to be regulated directly by blood levels of ACTH – presumably at the hypothalamic level.