Effects of metyrapone and dexamethasone on pro-gamma-melanotropin in healthy subjects

This study examined the effects of metyrapone and dexamethasone on circulating levels of pro-gamma-melanotropin (pro-γ-MSH) in normal healthy subjects. Pro-γ-MSH activity was investigated because of the peptide's probable role in acting synergistically with ACTH to stimulate cortisol production. In 21 healthy subjects, metyrapone challenge resulted in a significant increase of pro-γ-MSH values which paralleled the increase in circulating ACTH that occurred as cortisol levels fell. Post-metyrapone pro-γ-MSH and ACTH levels proved to be significantly correlated. While dexamethasone significantly suppressed plasma ACTH and cortisol levels, there was only a slight non-significant decrease in pro-γ-MSH values. Metyrapone testing has thus been shown to provide a powerful stimulus for pro-γ-MSH secretion, while the suppressant effects of dexamethasone on this peptide appear to be blunted and require further investigation.