RAT CORTICOSTATIN R4 - SYNTHESIS, DISULFIDE BRIDGE ASSIGNMENT, AND IN-VIVO ACTIVITY

We have synthesized significant amounts of the most potent member of t he rat corticostatins that inhibits ACTH-induced corticosteroid and co mpared its structure to that of the natural hormone. The cystine bridg ing arrangement that corresponds to that reported for a human defensin (3-31, 5-20, 10-30) was determined. The in vitro corticostatic activi ty of the synthetic rat corticostatin R4 paralleled that of the natura l R4. Biological studies in vivo showed that doses of 8 or 12 mg corti costatin/kg effectively interfered with corticosterone release in stre ssed rats. We conclude that in the assays that were used, the biologic al activity of the synthetic and natural molecules was identical. The availability of significant amounts of synthetic material will make po ssible studies investigating the physiological role played by corticos tatins in modulating the activity of the hypothalamic -pituitary-adren al axis.