Plasma steroid responses to circadian-stage-specified injection of different doses of the ACTH analogue alsactide (ACTH 1-17) in healthy adult human males

Abstract

Plasma cortisol, progesterone, testosterone and aldosterone levels were measured on serial blood samples drawn in 10 healthy adult human males up to 6h after single administration at about 07 of increasing amounts of the short-chain analogue ACTH-agonist alsactide (Synchrodyn 1-17). The following doses were employed: 2, 4, 8, 10 and 20 micrograms subcutaneously (s.c.), as well as 2, 4 and 8 micrograms intravenously (i.v.). Data were compared with those obtained by placebo (isotonic saline) injections. The s.c. injections of 2 and 4 micrograms resulted to be ineffective in changing the hormonal pattern. A significant rise of cortisol and progesterone, but not of aldosterone and testosterone, followed the s.c. injections of 8 and 10 micrograms. The differential pattern of the glucocorticoid vs. the mineralocorticoid response was also apparent after the s.c. injection of 20 micrograms alsactide; when compared with placebo, this dose was able to elicit a significant increase of all examined hormones except testosterone. All i.v. injections of 2, 4 and 8 micrograms alsactide were effective; the highest dose did cause a sustained rise of plasma cortisol, progesterone and aldosterone, but also the other doses were able to change significantly the mineralocorticoid levels. These results provide evidence that circadian-stage-specified s.c. or i.v. administration of the analogue can be employed in the clinical practice for enhancing selectively and transiently the morning glucocorticoid secretion.