Acetylation of adrenocorticotropin and beta-endorphin by hypothalamic and pituitary acetyltransferases.

Abstract

Acetylation of beta-endorphin- and adrenocorticotropin (ACTH)-related peptides was assessed in particulate fractions obtained from the neuro-intermediate lobe and anterior lobe of the pituitary gland and the hypothalamus of adult male rats. All three tissues acetylated ACTH(1-24), whereas only the neuro-intermediate lobe acetylated beta-endorphin and none of the tissues acetylated dynorphin. The apparent Km of the neuro-intermediate lobe enzyme for ACTH(1-24) and beta-endorphin was 1.6 and 22.3 microM, respectively; that of the anterior lobe and hypothalamic enzyme for ACTH(1-24) was 14.6 and 18.9 microM, respectively. N-acetylation appears to be the primary acetylation reaction of the neuro-intermediate lobe and hypothalamic enzyme. When the neuro-intermediate lobe enzyme was incubated in the presence of saturating concentrations of either ACTH(1-24) or ACTH(1-13)NH2 each mixed with beta-endorphin, acetylation of the peptide mixture equalled that seen in the presence of one peptide alone. These results are suggestive that the same neuro-intermediate lobe enzyme acetylates the N-terminal amino acid of both ACTH- and endorphin-related peptides and that this enzyme differs from the hypothalamic acetylating enzyme in its substrate specificity and apparent affinity for ACTH(1-24).