Stress-induced release of anterior pituitary hormones: Effect of H-3 receptor-mediated inhibition of histaminergic activity or posterior hypothalamiclesion

The effect of stress- or lipopolysaccharide (LPS) endotoxin-induced release of ACTH, beta-endorphin (beta-END) and prolactin (PRL) was investigated in two groups of conscious male rats: (1) Rats pretreated with different H-3 receptor agonists, which inhibit neuronal histamine (HA) synthesis and rele ase, and (2) rats with bilateral posterior hypothalamic lesion, which destr oys the histaminergic perikarya exclusively localized in the mammillary nuc lei. The Hg receptor agonists R(alpha)methyl-HA, BP 2-94 or Imetit injected intraperitoneally tip) had no effect on basal secretion of ACTH or PRL but inhibited the ACTH and PRL responses to restraint stress and the ACTH resp onse to LPS endotoxin. LPS had no effect on PRL secretion. The inhibitory e ffect of the agonists was prevented by prior ip administration of the He re ceptor antagonist thioperamide. Bilateral lesion of the posterior hypothala mus inhibited the ACTH, beta-END and PRL responses to restraint stress, eth er stress and LPS endotoxin, whereas sham operation had no effect compared to nonoperated control rats. In addition, posterior hypothalamic lesion inh ibited the PRL response but not the ACTH and B-END responses to activation of serotonergic neurons induced by ip administration of the 5-HT precusor 5 -hydroxytryptophan in combination with the 5-HT re-uptake inhibitor fluoxet ine. Thus, serotonergic pathways were not damaged by the lesions. The present results support our previous findings that inhibition of neuron al HA synthesis by alpha-fluoromethyl-histidine as well as blockade of H-1 or H-2 receptors inhibit the ACTH, beta-END and PRL responses to stress and LPS endotoxin and further substantiate an important role of histaminergic neurons in the mediation of the stress-induced release of pituitary stress hormones. Furthermore, in accordance with our previous findings, the lesion experiments indicated the existence of an interaction between the histamin ergic and serotonergic system in regulation of the stress- and LPS-induced PRL release.