The corticostatic (anti-ACTH) and cytotoxic activity of peptides isolated from fetal, adult and tumor-bearing lung

Abstract

The possibility that corticosteroids influence lung maturation was suggested in 1968 by Buckingham et al. and supported by studies mounted in humans and in rabbits by Liggins and Howie and by a collaborative study from the N.I.H. To our knowledge no reverse process, i.e. the regulation of adrenal function by the lung, has been postulated. In attempting to isolate ACTH from fetal lung we found peptides which depressed corticosterone production. Eventually, we isolated a group of peptides from rabbit fetal lung which showed potent inhibition of corticosterone production in rat adrenal cell suspensions. Using high-resolution reverse-phase HPLC and high-sensitivity gas-phase sequencing techniques the primary structure of one of these peptides has been determined and it was called corticostatin. The adult rabbit lung contains a large quantity of a very similar peptide, which elutes close to corticostatin but whose amino acid composition differs by a single glycine and possibly a serine. This peptide is also potently corticostatic. We have isolated homologous human peptides but these show no apparent corticostatic activity in rat adrenal cell suspensions. They do, however, show interesting effects on in vitro growth of lung cell lines.