Demonstration of corticotrophin-releasing activity in rat and human peripheral blood.

Corticotrophin-releasing activity of rat or human peripheral blood was examined with a sensitive in vitro CRF bioassay, using cultured rat adenohypophyseal cells and ACTH measurement by radioimmunoassay. A dose-related ACTH secretion into the medium occurred in response to plasma or serum obtained from unstressed rats or humans. The minimum effective dose was 2.5 mul (0.1% of the medium concentration). No concomitant release of TSH occurred, indicating that cellular destruction was not the source of ACTH in the medium. As previously found with hypothalamic extract, 50% of the maximum ACTH secretion produced by a given quantity of plasma occurred within 1-5 min. Fifty per cent of CRF activity was retained after plasma was boiled for 5 min. CRF activity of serum was not different in intact, 1-10 min ether-stressed, adrenalectomized, hypophysectomized or dexamethasone-treated rats. There was no significant difference in CRF activity between serum from intact rats and those with complete forebrain removal and hypophysectomy, indicating that serum CRF originates from a source outside the forebrain or pituitary. Because of the lack of correlation of blood CRF activity with conditions in which there are marked differences in in vivo ACTH concentration, it is possible that the blood CRF activity we measure is non-specific.