title: Does reduction of circulating prostaglandin E2 reduce fetal hypothalamic-pituitary-adrenal axis activity?
abstract: OBJECTIVE
  Placental production of prostaglandin E2 (PGE2) increases in fetal sheep as term approaches. It has been suggested that placental PGE2 may act as a hormone to activate the fetal hypothalamic-pituitary-adrenal (HPA) axis. Alternatively, we have proposed that local generation of prostaglandins in the fetal brain and/or pituitary might play a more prominent role in the stimulation of fetal adrenocorticotropin (ACTH) secretion. We performed the present experiments to test the hypothesis that the elevated concentrations of PGE2 in fetal plasma do not tonically stimulate fetal ACTH secretion.
  
  
  METHODS
  We studied chronically catheterized late-gestation fetal sheep. Selective inhibitors of prostaglandin synthase-1 and -2 (PGHS-1 and PGHS-2) were injected intravenously. Fetal blood pressure and heart rate were monitored continuously, and circulating concentrations of PGE2, ACTH, and cortisol were measured by specific immunoassay.
  
  
  RESULTS
  Injection of vehicle did not have an effect on circulating levels of PGE2 or ACTH, but it did have a mild stimulatory effect on cortisol. The selective PGHS-2 inhibitor, Nimesulide (Cayman Chemical, Ann Arbor, MI), significantly decreased plasma PGE2 concentrations. The selective PGHS-1 inhibitor, Resveratrol (Cayman Chemical), produced smaller decreases in plasma PGE2 concentrations and significantly increased mean arterial blood pressure. Neither inhibitor significantly altered plasma ACTH or cortisol concentrations.
  
  
  CONCLUSIONS
  These results demonstrate that reduction of circulating PGE2 concentrations in response to intravenous injection of PGHS-1 and PGHS-2 inhibitors does not reduce fetal HPA axis activity. We conclude that PGE2 in late-gestation ovine fetal plasma does not tonically stimulate fetal ACTH secretion.
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, Florida 32610-0274, USA.
authors.forename: Sharon K
authors.initials: SK
authors.lastname: Reimsnider
authors.forename: Charles E
authors.initials: CE
authors.lastname: Wood
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D015232:Dinoprostone / Q000097:blood* / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006340:Heart Rate, Fetal; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008431:Maternal-Fetal Exchange; D010913:Pituitary-Adrenal System / Q000502:physiology*; D010920:Placenta / Q000502:physiology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D000077185:Resveratrol; D012756:Sheep; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D013267:Stilbenes; D013449:Sulfonamides; D000324:Adrenocorticotropic Hormone; D015232:Dinoprostone; D000077185:Resveratrol; C012655:nimesulide; D006854:Hydrocortisone