HISTAMINERGIC ACTIVATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS

Centrally administered histamine (HA) stimulates the secretion of aden ohypophysial POMC-derived peptides, which subsequently cause release o f corticosterone. The effect of HA on POMC-derived peptide release is indirect, and it is possible that hypothalamic neurons containing cort icotropin-releasing hormone (CRH), arginine vasopressin (AVP), or oxyt ocin (OT) are involved in the mediation of this response. We studied t he effect of HA on: 1) expression of CRH, AVP, and OT messenger RNA (m RNA) at the hypothalamic level; 2) expression of c-fos and POMC mRNA a t the pituitary level; and 3) peripheral plasma levels of AVP, OT, ACT H, beta-endorphin (beta-END), and corticosterone. HA (270 nmol) infuse d intracerebroventricularly increased the expression of CRH, AVP, and OT mRNA in the paraventricular nucleus as well as that of OT mRNA in t he supraoptic nucleus of the hypothalamus. At the pituitary level the expression of mRNA for c-fos and POMC increased in the anterior but no t in the intermediate lobe in response to HA. Plasma levels of AVP, OT , ACTH, beta-END, and corticosterone all increased in response to cent ral HA administration. Circulating levels of AVP and OT peaked after 5 min, ACTH and beta-END after 15 min, whereas corticosterone levels we re highest after 30 min. In concert with our earlier discoveries, the present data support the hypothesis that HA-induced secretion of ACTH and beta-END is mediated via central activation of hypothalamic neuroe ndocrine neurons containing CRH, AVP, and/or OT.