Stimulation of adrenal cortisol biosynthesis by epidermal growth factor

The effect of epidermal growth factor (EGF) on adrenal cortisol biosynthesis in ewes was determined both in vivo and in vitro. There was a progressive rise in plasma cortisol levels after infusion of 2.9 micrograms/kg/h EGF into 5 ewes over 24 h. Mean plasma cortisol rose to a sustained plateau of 700% of the saline control value and fell towards saline control values before the end of the infusion. In vitro, adrenal slices taken from ewes synthesized and released significantly greater amounts of cortisol in response to the addition of EGF or ACTH1-24. EGF and ACTH1-24 gave a maximal stimulation of cortisol biosynthesis between 10 and 100 ng/ml and above 100 ng/ml, respectively. Biologically inactive reduced S-carboxyamidomethyl EGF as well as a number of polypeptide hormones and growth factors were without effect at these dose levels. Stimulation by EGF of cortisol synthesis and secretion was dependent on protein synthesis as it was for ACTH. However, EGF did not synergise with ACTH in promoting cortisol production. These results suggest that EGF may be a regulatory factor affecting adrenal cortisol synthesis and secretion.