Central bombesin activates the hypothalamic-pituitary-adrenal axis: Effects on regional levels and release of corticotropin-releasing hormone and arginine-vasopressin

While corticotropin-releasing hormone (CRH) is a primary regulator of the hypothalamic-pituitary-adrenal (HPA) axis, the mechanism(s) triggering the release of this corticotropin (ACTH) secretagogue remains unknown. Stressful and appetitive events evoke the release of not only CRH but also of bombesin (BN)-like peptides. Furthermore, CRH antagonists attenuate the endocrine and behavioral effects of BN, suggesting that BN-like peptides may mediate their effects via CRH release. An initial (mapping) study revealed that centrally administered BN (0.25 or 0.5μg i.c.v.) increased circulating corticosterone and ACTH levels and decreased immunoreactive (ir)-CRH at the nucleus of the solitary tract, ventromedial (VMH) and anterior hypothalamic nuclei, and the central amygdaloid nucleus. Whereas BN treatment decreased ir-vasopressin (AVP) at the VMH, it elevated levels of this peptide in the hypothalamic paraventricular and median eminence/arcuate (Me/Arc) regions. Dynamic, in vivo release experiments (using push-pull perfusion) revealed that BN evoked the release of ir-CRH and ir-AVP from the Me/Arc and increased interstitial levels of these secretagogues at the anterior pituitary. These results suggest that BN-like peptides may regulate certain hypothalamic and extrahypothalamic circuits, including the HPA axis, by affecting regional utilization of ir-CRH and ir-AVP, and/or by provoking the release of these peptides at the Me/Arc, thus increasing their availability downstream at the anterior pituitary and increasing circulating ACTH and corticosterone levels.