Adrenocorticotropic Effects of a Synthetic Polypeptide—β1–24-Corticotropin—in Man

Abstract

Evidence is presented suggesting that the synthetic tetracosapeptide—β^1–24-corticotropin—stimulates the synthesis and release of certain adrenal steroids in man. Thus, parenteral administration was associated with an increase in plasma cortisol levels, a raised excretion of 17-ketosteroids and 17-hydroxysteroids and a fall in the eosinophil count and urinary sodium /potassium ratio. Similar and maximal rates of increase in the concentration of plasma cortisol resulted from the infusion of 100 μg/hr of the synthetic polypeptide and of 10 IU/hr of highly purified corticotropin, both in control subjects and in patients with glucocorticoidinduced adrenal atrophy. The tetracosapeptide was found to elicit a maximal adrenal response when infused at a rate of 3 μg/hr, or more, while the infusion of 2 μg/hr, or less, was not associated with a significant increase of plasma cortisol concentrations. Between these 2 infusion rates the response varied reproducibly with dose. Comparable results were obtained in 1 subject during the infusion of 2.3 μg/hr of β^1–24-corticotropin and 0.20 IU/hr of the natural hormone. In 2 patients sensitive to porcine corticotropin the infusion of the tetracosapeptide was not associated with hypersensitivity reactions. This was attributed to the freedom from the risk of contamination by foreign proteins and the fact that its amino acid sequence is common to corticotropins of various species. The duration of adrenal stimulation following a single intravenous or intramuscular injection of the synthetic polypeptide was shorter than that observed following the single injection of a comparable amount of porcine corticotropin. Thus, it would appear that the longer amino acid sequence of the natural hormone delays its intravascular inactivation.