{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T17:56:23Z","timestamp":1784915783297,"version":"3.55.0"},"reference-count":38,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:p> Prostaglandins, generated within the fetal brain, are integral components of the mechanism controlling the fetal hypothalamus-pituitary-adrenal (HPA) axis. Previous studies in this laboratory demonstrated that prostaglandin G\/H synthase isozyme 2 (PGHS-2) inhibition reduces the fetal HPA axis response to cerebral hypoperfusion, blocks the preparturient rise in fetal plasma ACTH concentration, and delays parturition. We also discovered that blockade of N-methyl-d-aspartate (NMDA) receptors reduces the fetal ACTH response to cerebral hypoperfusion. The present study was designed to test the hypothesis that PGHS-2 action and the downstream effect of HPA axis stimulation are stimulated by NMDA-mediated glutamatergic neurotransmission. Chronically catheterized late-gestation fetal sheep ( n = 8) were injected with NMDA (1 mg iv). All responded with increases in fetal plasma ACTH and cortisol concentrations. Pretreatment with resveratrol (100 mg iv, n = 5), a specific inhibitor of PGHS-1, did not alter the magnitude of the HPA axis response to NMDA. Pretreatment with nimesulide (10 mg iv, n = 6), a specific inhibitor of PGHS-2, significantly reduced the HPA axis response to NMDA. To further explore this interaction, we injected NMDA in six chronically catheterized fetal sheep that were chronically infused with nimesulide ( n = 6) at a rate of 1 mg\/day into the lateral cerebral ventricle for 5\u20137 days. In this group, there was no significant ACTH response to NMDA. Finally, we tested whether the HPA axis response to prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>) is mediated by NMDA receptors. Seven chronically catheterized late-gestation fetal sheep were injected with 100 ng of PGE<jats:sub>2<\/jats:sub>, which significantly increased fetal plasma ACTH and cortisol concentrations. Pretreatment with ketamine (10 mg iv), an NMDA antagonist, did not alter the ACTH or cortisol response to PGE<jats:sub>2<\/jats:sub>. We conclude that generation of prostanoids via the action of PGHS-2 in the fetal brain augments the fetal HPA axis response to NMDA-mediated glutamatergic stimulation. <\/jats:p>","DOI":"10.1152\/ajpregu.00163.2010","type":"journal-article","created":{"date-parts":[[2010,5,5]],"date-time":"2010-05-05T22:20:31Z","timestamp":1273098031000},"page":"R365-R370","source":"Crossref","is-referenced-by-count":12,"title":["Interaction of PGHS-2 and glutamatergic mechanisms controlling the ovine fetal hypothalamus-pituitary-adrenal axis"],"prefix":"10.1152","volume":"299","author":[{"given":"Nathan","family":"Knutson","sequence":"first","affiliation":[{"name":"Departments of Pediatrics and Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles E.","family":"Wood","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Physiology and Functional Genomics, 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