Anterior pituitary hormone responses to a kappa-opioid agonist in man

The present study was designed to investigate pituitary hormone responses to a kappa-opiate receptor agonist in man. Normal men were given the racemic benzomorphan kappa-agonist MR 2033 or its levorotatory isomer MR 2034 iv. Plasma levels of PRL and GH markedly increased after injection of 3.5 micrograms/kg MR 2033 or 1.9 or 3.8 micrograms/kg MR 2034. These effects of MR 2033 were blocked by the opiate antagonist naloxone (10 mg), thereby demonstrating their mediation by opiate receptors. The kappa-agonist did not change plasma levels of LH and FSH. The secretion of TSH was significantly suppressed by MR 2033 and MR 2034, but this action was not antagonized by pretreatment with naloxone. The suppression of plasma TSH was, however, stereospecific since the (+)-isomer, MR 2035, did not affect TSH secretion. These data indicate that kappa-opiate receptors are located on neuronal pathways regulating GH, TSH, and PRL secretion. The pattern of pituitary responses elicited by the kappa-agonist differs from that of mu-opioid agonists, indicating differential endocrine functions for the endogenous agonists.