Involvement of oxytocin in histamine- and stress-induced ACTH and prolactin secretion.

Abstract

The neurohypophysial peptide oxytocin (OT) is released in response to different stressors and has been suggested as a 'stress hormone'. In addition, we have recently shown that centrally administered histamine (HA), which is a mediator of stress-induced release of ACTH and prolactin (PRL), stimulates OT secretion. The aim of the present investigation was to further characterize the HA-induced OT secretion with respect to the type of postsynaptic receptor involved and to investigate the possible role of OT in HA- and stress-induced ACTH and PRL secretion. We studied (1) the effect of HA, HA agonists and HA antagonists on OT secretion in normal male rats, (2) the secretion of OT in response to HA stimulation and to restraint stress, endotoxin stress [lipopolysaccharide (LPS) administration] and insulin/hypoglycemia stress and compared the OT response to that of arginine vasopressin (AVP), (3) the OT response to restraint stress or HA in normal and AVP-deficient Brattleboro rats (DI) suffering from diabetes insipidus and (4) the effect of inhibiting the oxytocinergic system by immunoneutralization or receptor blockade on HA- and stress-induced ACTH and PRL release in normal as well as in DI rats. HA, an H1 and an H2 receptor agonist, stimulated the OT secretion dose-dependently. The HA-induced release of OT was inhibited by pretreatment with an H1 or an H2 receptor antagonist. Restraint stress and HA but not LPS or insulin stress induced an increase in peripheral OT levels, whereas only LPS stress and HA caused an increase in circulating AVP levels. Neither an OT antiserum nor an OT antagonist inhibited the HA- or restraint-stress-induced ACTH or PRL release in normal rats. AVP-deficient DI rats showed, in comparison with their nondeficit counterparts, an increased basal level of OT and no increase in OT levels following restraint stress, whereas the OT response to HA was similar in the two rat types. In AVP-deficient rats immunoneutralization of OT had no inhibitory effect on the HA- and restraint-stress-induced ACTH and PRL response. The ACTH and PRL response to restraint stress and the ACTH response to HA was impaired in DI rats compared to their healthy controls. We conclude (1) that HA stimulates OT secretion via activation of postsynaptic H1 and H2 receptors, and (2) that, in contrast to AVP, OT does not seem to be involved in HA- and restraint-stress-induced ACTH and PRL secretion.