Arachidonic acid metabolites modulate rat hypothalamic corticotropin-releasing hormone secretion in vitro.
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.
Bernardini
R
R
Developmental Endocrinology, Branch, NICHD, Bethesda, Md.
Chiarenza
A
A
Calogero
A E
AE
Gold
P W
PW
Chrousos
G P
GP
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
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