Release of ACTH by Substances of Central Nervous System Origin

Abstract

The ACTH-releasing activity of some substances of low molecular weight was tested in several assay systems in the rat, in which attempts were made to block the nonspecific release of ACTH. The rate of corticosteroid production in vitro and corticosterone content of plasma were used as parameters of pituitary ACTH release. In the rat pretreated with sodium pentobarbital and chlorpromazine, none of the amino acids, amino acid mixtures, various di- and tripeptides, or biogenic amines exhibited a significant effect on pituitary-addrenal activity. However, prostaglandin E1 and E2, in contrast to F1α and F2α, stimulated pituitary ACTH release in rats blocked with sodium pentobarbital and chlorpromazine. Angiotensin II, arginine vasopressin, carbachol and a crude CRF from calf brain also activated the pituitary-adrenal system of similarly blocked rats. The corticotrophic effect of these “active agents” was further studied in rats pretreated with sodium pentobarbital, atropine and chlorpromazine; sodium pentobarbital and morphine; chlorpromazine, morphine and sodium pentobarbital; dexamethasone and sodium pentobarbital; in neurohypophysectomized rats pretreated with sodium pentobarbital; in rats bearing extensive lesions in the median eminence of the hypothalamus, and on the release of ACTH from isolated anterior pituitaries in vitro. The anterior pituitary in vitro was the only assay system in which the crude CRF was the sole material which effectively triggered the release of ACTH. The other assay systems failed to discriminate between the crude CRF and the other active agents in that generally 2 or more compounds were capable of stimulating pituitary ACTH release. These results indicate that the isolation of the CRF is hampered by the lack of specific and sensitive in vivo assay systems. (Endocrinology85: 561, 1969)