Corticotropin synthesis and secretion is under negative feedback regul
ation by glucocorticoids. In addition a hypothalamic factor inhibiting
ACTH synthesis and secretion, named corticotropin release inhibiting
factor (CRIF), has been postulated but not identified. Here we report
that transient transfection of a rat prepro-TRH cDNA into the mouse an
terior pituitary tumor cell line AtT-20 inhibits the synthesis and sec
retion of both basal and CRH-stimulated ACTH. Thus, CRTF appears to be
encoded by the same precursor as TRH, suggesting a coordinated regula
tion of pituitary-adrenal and pituitary-thyroid functions.