title: 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) F2 alpha or E2, thromboxane (TX) B2, the TXA2 receptor agonist U-49,619 and leukotrienes (LT) B4, C4 and D4 at concentrations ranging from 10(-15) to 10(-5) M. 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 less than 0.05). The concentration of 10(-11) M dexamethasone 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 PGF2 alpha-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 PGF2 alpha, 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.
authors.affiliation: Developmental Endocrinology, Branch, NICHD, Bethesda, Md.
authors.forename: R
authors.initials: R
authors.lastname: Bernardini
authors.forename: A
authors.initials: A
authors.lastname: Chiarenza
authors.forename: A E
authors.initials: AE
authors.lastname: Calogero
authors.forename: P W
authors.initials: PW
authors.lastname: Gold
authors.forename: G P
authors.initials: GP
authors.lastname: Chrousos
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D046508:Culture Techniques; D003907:Dexamethasone / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D015777:Eicosanoids; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007975:Leukotriene B4 / Q000494:pharmacology; D008297:Male; D011448:Prostaglandin Antagonists; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013189:SRS-A / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D013929:Thromboxane B2 / Q000494:pharmacology
chemical_list: D001095:Arachidonic Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015777:Eicosanoids; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011448:Prostaglandin Antagonists; D011982:Receptors, Prostaglandin; D013189:SRS-A; C062714:U 49619; D007975:Leukotriene B4; D016718:Arachidonic Acid; D012701:Serotonin; D013929:Thromboxane B2; D013928:Thromboxane A2; D003907:Dexamethasone; C045749:SQ 29548; D003346:Corticotropin-Releasing Hormone; D015237:Dinoprost; D007770:L-Lactate Dehydrogenase; D015232:Dinoprostone; D000109:Acetylcholine; D007213:Indomethacin