Prostaglandin E2 stimulates adrenocorticotrophin and cortisol secretion via a hypothalamic site of action in fetal sheep.
The hypothesis that prostaglandins stimulate fetal adrenocortical activity via a central site of action within the fetal brain was tested in chronically catheterized fetal sheep. At day 120 gestation (term = 145 days) fetal sheep were surgically prepared with catheters in the lateral cerebral ventricle, jugular vein and carotid artery and experiments began five days later. Intravenous (i.v.) infusion of prostaglandin E2 (30 or 120 micrograms.h-1) caused a significant dose-related increase in fetal plasma concentrations of ACTH. Despite this increase in ACTH, cortisol was only stimulated after the highest dose of prostaglandin E2. Intracerebroventricular (i.c.v.) infusion of PGE2 (30 micrograms.h-1) also stimulated ACTH secretion although the peak response was delayed and considerably less compared with the same dose administered intravenously. Prostaglandin F2 alpha administered i.v. or i.c.v. had no effect on circulating concentrations of either ACTH or cortisol. These data provide evidence that prostaglandin E2 can stimulate fetal ACTH secretion by acting in the fetal brain. Furthermore, the greater release of ACTH after i.v. compared with i.c.v. prostaglandin E2 suggests that a site of action other than the brain, such as the pituitary gland, may also be important. These results provide further evidence that during late gestation circulating prostaglandins can act to stimulate fetal pituitary-adrenal maturation.
Brooks
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AN
MRC Reproductive Biology Unit, Edinburgh, Scotland.
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000818:Animals; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood / Q000378:metabolism; D005333:Fetus / Q000502:physiology*; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D009994:Osmolar Concentration; D012756:Sheep; D013997:Time Factors
D000324:Adrenocorticotropic Hormone; D015232:Dinoprostone; D006854:Hydrocortisone