Role of prostaglandins in the stimulation of the hypothalamic-pituitary-adrenal axis by adrenergic and neurohormone systems

Abstract

Role of the prostaglandins (PGs) in the activation of the hypothalamic-pituitary-adrenal (HPA) axis by the adrenergic agonists, corticotropin-releasing hormone (CRH) and vasopressin (VP) in rats under basal and social stress conditions was investigated. Systemic or intracerebroventricular (icv) pretreatment with indomethacin powerfully reduced the corticosterone response to ivc phenylephrine, and alpha 1-receptor agonist, significantly diminished the response to clonidine, an alpha 2-receptor agonist, but did not alter the response to isoprenaline, a beta-adrenergic agonist. Consequently, indomethacin considerably reduced the corticosterone response to noradrenaline, and alpha 1- and alpha 2-adrenergic agonist, but did not change the response to adrenaline, a predominant beta-adrenergic agonist. Thus, prostaglandins considerably mediate the HPA activity stimulated via central alpha 1- and alpha 2- but not beta-adrenergic receptors. Social crowding stress for 3 days did not affect the corticosterone response to ip or icv CRH, but drastically reduced the response to VP. In stressed rats indomethacin did not alter the corticosterone response to CRH but significantly further impaired the diminished by stress corticosterone response to VP. Neither social stress nor endogenous prostaglandins affected the responsiveness of the CRH system. By contrast, both social stress and prostaglandins considerably diminished the HPA response to VP. The above results indicate that both these neurohormone systems have a distinct mode of adaptation and interaction with PG systems during social stress. Interleukins, particularly IL-1 beta and IL-6, activate the HPA axis. Most immunological stimuli and interleukins also activate both the central and the peripheral noradrenergic systems. Activation of the HPA axis in vivo depends on the secretion of CRH, an intact pituitary and the ventral adrenergic bundle innervating the hypothalamic paraventricular nucleus. Interleukins may cross the blood-brain-barrier or be produced in the CNS to stimulate their receptors in brain structures involved in the regulation of the HPA axis.