Arachidonic Acid Metabolites Modulate Rat Hypothalamic Corticotropin-Releasing Hormone Secretion in vitro

Abstract

Arachidonic acid metabolites have been shown to modulate the secretion of various hormones, including luteinizing hormone, growth hormone and adrenocorticotropin. In this paper we describe the effect of a series of eicosanoids on hypothalamic secretion of corticotropin-releasing hormone (CRH) in vitro. Explanted rat hypothalami in culture were exposed to prostaglandins (PG) F_2α or E₂, thromboxane (TX) B₂, the TXA₂ receptor agonist U-49,619 and leukotrienes (LI) B₄, C₄ and D₄ at concentrations ranging from 10^–15 to 10^–5M. PGE₂, LTD₄ and TXB₂ did not alter hypothalamic CRH secretion. On the other hand, the remaining eicosanoids tested induced a significant increase of hypothalamic CRH secretion (p < 0.05). The concentration of 10-nM dexa-methasone inhibited the effect of stimulatory eicosanoids on CRH secretion. The CRH response to U-49,619 was completely prevented by the TXA₂ receptor antagonist SQ-29,548. The latter also inhibited serotonin (5-HT)-, acetylcholine (ACh)- and PGF_2α-induced CRH release. Indomethacin was capable of blocking the secretion of CRH induced by 5-HT and ACh. In addition, PGE₂ inhibited the increase of CRH secretion induced by PGF_2α, 5-HT and ACh. These findings suggest that eicosanoids may be involved in the regulation of hypothalamic CRH secretion, either as autocrine/paracrine or as endocrine factors.

Defective hypothalamic response to immune and inflammatory stimuli in patients with rheumatoid arthritis

“…CRH secretion has been shown to be modulated in vitro by prostanoids and platelet activating factor, in studies using rat tissues (29)(30)(31). Since the long-term use of NSAIDs by RA patients and NIAIOA controls was comparable in this study, the use of these agents and prostaglandin effects cannot explain the observed hypothalamic defect (Tables 1 and 2).…”

Brain cyclooxygenase and prostanoid TP receptors are involved in centrally administered epibatidine-induced secretion of noradrenaline and adrenaline from the adrenal medulla in rats

“…Prostanoids (prostaglandins and thromboxane A 2 ) generated by several enzymes, including cyclooxygenase, have been demonstrated to act as a neurotransmitter and/or neuromodulator in the brain's actions such as cardiovascular function (Wood et al, 1993;Zhang et al, 2003) and regulation of hormone secretion (Bernardini et al, 1989;Reimsnider and Wood, 2006). Previously, we reported that central pretreatment with indomethacin or ketoprofen (inhibitors of cyclooxygenase) attenuated the centrally administered CRF-, vasopressin-, histamine-, GLP-1-and bombesin-induced elevation of plasma noradrenaline and adrenaline (Okada et al, 2003;Shimizu et al, 2006;Arai et al, 2008;Lu et al, 2008), suggesting the involvement of the brain prostanoids in these substances-induced elevation of plasma catecholamines in rats.…”

Organization and Integration of the Endocrine System: The Arousal and Sleep Perspective

“…Also, it is quite likely that each of these cytokines might initiate a cascade of paracrine and autocrine events with sequential secretion of local mediators of inflammation by nonfenestrated endothelial cells, glial cells, cytokinergic neurons, or all three, resulting in activation of CRH-and AVP-secreting neurons. [112][113] Some of the activating effects of inflammation on the HPA axis may be exerted indirectly through stimulation of the central noradrenergic pathways by the inflammatory cytokines and other humoral mediators of inflammation. Also, activation of peripheral nociceptive, somatosensory, and visceral afferent fibers would lead to stimulation of both the catecholaminergic and the CRH neuronal systems via ascending spinal pathways.…”

“…Thus, several eicosanoids, platelet-activating factor, and epidermal growth factor have strong CRH-releasing abilities. [112,113,118]It is not clear, however, which of the effects are endocrine and which are paracrine. Direct effects, albeit delayed, of most of these cytokines and mediators of inflammation on pituitary ACTH and adrenocortical glucocorticoid secretion have also been shown.…”