Preprothyrotropin-releasing hormone-(178-199) does not inhibit corticotropin release

Pituitary ACTH synthesis and secretion are positively regulated by hypothalamic factors and negatively regulated by adrenal corticosteroids. Negative hypothalamic regulation of pituitary ACTH synthesis and secretion has been postulated, but not proved. The search for a hypothalamic corticotropin release-inhibiting factor has recently focused on peptides derived from the prepro-TRH precursor of TRH. One of the peptides, prepro-TRH-(178-199), was reported to suppress basal and stimulated ACTH release. We examined the effects of prepro-TRH-(178-199) alone and in combination with CRH and corticosterone, two known physiologic regulators of ACTH secretion. Prepro-TRH-(178-199) had no effect on basal, stimulated, or attenuated ACTH release from cells that responded normally to CRH and/or corticosterone. These results indicate that prepro-TRH-(178-199) is not a corticotropin release-inhibiting factor.