Distribution, plasma concentration, and in vivo prolactin-releasing activity of peptide histidine methionine in humans.

ABSTRACT

The distribution of immunoreactive peptide histidine methionine (PHM) in human tissues and its plasma concentrations were examined using a specific RIA and gel filtration chromatography. The effects of synthetic PHM on anterior pituitary hormone secretion also were studied. Immunoreactive PHM was found in all tissues studied; high concentrations were found in the gastrointestinal tract, lung, and parotid gland. Subsequent but smaller amounts of PHM were found in the hypothalamus, pituitary stalk, olfactory lobe, and cerebral cortex. The distribution of immunoreactive PHM in human tissues was very similar to that of vasoactive intestinal polypeptide (VIP), and PHM and VIP were in equimolar concentrations. Immunoreactive PHM was also detectable in plasma of normal subjects, and similar plasma concentrations were found in patients with prolactinomas. Molecular sieve chromatography of extracts of nonneural tissues and plasma extracts revealed only one peak, eluting in the position of synthetic PHM. Two peaks of immunoreactive PHM were found in brain tissue; one coeluted with synthetic PHM, and the other eluted in the high mol wt region. Bolus injections of synthetic PHM significantly increased plasma PRL levels in a dose-dependent manner. However, PHM did not alter plasma GH, TSH, ACTH, LH, or FSH levels. These results indicate that PHM is distributed widely in human tissues, and posttranslational processing of the VIP-PHM precursor molecule may be different in different tissues. The finding of equimolar distributions of PHM and VIP is consistent with the notion that these two peptides are synthesized from a common precursor. The presence of immunoreactive PHM in human hypothalamic and pituitary stalk tissue and its specific in vivo PRL-releasing activity suggest that PHM may play an important role in the regulation of PRL secretion.