An analogue of met-enkephalin attenuates the pituitary-adrenal response to ovine corticotrophin releasing factor.

The met-enkephalin analogue, DAMME, suppresses the pituitary-adrenal axis in normal subjects; it is not clear whether this occurs at the level of the pituitary or above. We therefore administered synthetic ovine corticotrophin releasing factor (CRF-41) 100 micrograms i.v. to a group of normal male subjects, with or without pretreatment with DAMME 250 micrograms i.v., and monitored the response of plasma ACTH and serum cortisol. CRF-41 caused a marked stimulation of ACTH and cortisol release, but this was significantly attenuated by pretreatment with DAMME. It is therefore concluded that DAMME either directly inhibits the corticotroph at the level of the pituitary, or that it suppresses release of an additional factor which normally potentiates the action of CRF-41 on the pituitary.