Corticotropin releasing factor induction of leukocyte-derived immunoreactive ACTH and endorphins

Human peripheral leukocytes^1,2 infected by virus or treated with endotoxin will, like unstimulated mouse spleen macrophages³, synthesize immunoreactive corticotrophin (ir-ACTH) and endorphins. The ir-ACTH produced appears to be identical with authentic ACTH^1-6, while enough of the material has been produced in hypophysectomized mice infected with virus to demonstrate a steroidogenic reponse⁶. Because the production of ACTH by in vivo pituitary cells and by leukocytes is suppressed by dexamethasone both in vitro⁷ and in vitro⁶, suggesting⁸ that the production of ACTH and endorphins by leukocytes is indeed controlled, we have investigated the effects of corticotropin releas-ing-f actor (CRF), which is known⁹ to regulate the pituitary production of both ACTH and β-endorphin. We now report that the production of ACTH and endorphins by leukocytes is indeed induced by synthetic CRF¹⁰ and, in turn, suppressed by dexamethasone, suggesting that, as in pituitary cells, the pro-opiomelanocortin (POMC) gene may be expressed and similarly controlled in leukocytes.