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Relationships Between the Structure and Biological Activities of Corticotropin and Related Peptides: Biological Activities of a Synthetic Eicosapeptide Amide¹

Departments of Medicine and Physiology, and Division of Endocrinology, Duke University School of Medicine Durham, North Carolina

Supported by grants from the American Cancer Society (P166C) and the Institute of Arthritis and Metabolic Diseases (A1324), USPHS, and by Contract DA-49-193-MD-2153, the Medical Research and Development Division, Office of the Surgeon General, Department of the Army.

Abstract

The synthetic eicosapeptide amide of Hofmann, comprising the N-terminal sequence 1 to 20 of corticotropin A₁S, in which the twentieth amino acid valine is in the form of the amide, has been investigated for adrenal and extra-adrenal effects by in vivo and in vitro techniques. The adrenal activities assayed were in vivo steroidogenesis in 24-hr hypophysectomized rats and in vitro steroidogenesis by quartered rat adrenals. The in vitro release of free fatty acids by rat epididymal adipose tissue and the mobilization of free fatty acids and the depression of blood sugar in the intact mouse were the extraadrenal effects measured. All activities were assayed relative to corticotropin A₁ on a weight basis. The activities of the eicosapeptide amide in the in vitro assays were steroidogenesis, 181%, adipokinetic effect, 160%, and hypoglycemia, 200%. By in vitro techniques the steroidogenic effect was 78% and the adipokinetic effect was 39%. Thus, by in vivo assays the eicosapeptide amide has the same molar activity as corticotropin in both adrenal and extra-adrenal effects. This is the minimum chain length which has been shown to have full corticotropin activity. The comparison of in vivo and in vitro assays showed that in vitro techniques may give erroneous estimates of the true biological activity of a synthetic peptide, presumably because of instability of the peptides in in vitro systems. (Endocrinology 75: 831,1964)

Footnotes

¹ Part of this material was presented at the 1963 Meeting of The Endocrine Society.

² Work done during tenure of a traineeship from the Institute of Arthritis and Metabolic Diseases, NIH.

³ Deceased.

Received July 24, 1963.