Effect of 3 day infusion of ACTH or CRF on the pituitary-adrenal axis

1. The effects of 72 h subcutaneous infusion of graded doses of rat CRF and ACTH(1-24) were studied in rats of initial weight 150-170 g. Rat CRF was infused at 30, 100 or 300 ng/h, and ACTH(1-24) at 125, 250 or 500 ng/h. 2. There was a progressive though modest increase in adrenal weight for all CRF doses, and an associated reduction of thymus weight. Circulating ir-ACTH, ir-beta-endorphin and corticosterone levels, and adrenal DNA content, were not increased after 3 days. Adrenal RNA and protein content were increased at the highest CRF dose used. 3. ACTH infusion caused a progressive increase in adrenal weight and thymic involution which was marked at the higher doses; circulating corticosterone levels were not significantly altered by the lowest dose but were significantly raised by the higher doses. As expected, plasma ir-beta-endorphin was suppressed to low levels with all doses. Adrenal DNA did not alter but there were progressive increases in adrenal protein and RNA. 4. There was a marked difference in gain between the two infusion regimens in terms of all parameters measured, suggesting that potent mechanisms exist to temper the pituitary-adrenal response to markedly different levels of peripheral CRF input. The damped effect of CRF infusion compared with that of ACTH may represent desensitization of CRF receptors at the pituitary; alternatively, it may reflect binding and substantial inactivation of CRF in peripheral blood.