Aims
Both prostaglandin E2 (PGE2) and estradiol stimulate fetal ACTH secretion and augment fetal ACTH responses to stress. We have reported that estradiol increases prostaglandin endoperoxide synthase-2 (PGHS-2), and we have proposed that there is a positive feedback relationship between estrogen and fetal hypothalamus-pituitary-adrenal (HPA) axis activity that is dependent upon PGHS activity in the fetal brain. The present study was designed to test the hypothesis that blockade of estrogen receptors in the fetal brain decrease PGHS-2 expression and reduces fetal HPA axis activity.
Background/aims
Both prostaglandin E2 (PGE2) and estradiol stimulate fetal ACTH secretion and augment fetal ACTH responses to stress. We have reported that estradiol increases prostaglandin endoperoxide synthase-2 (PGHS-2), and we have proposed that there is a positive feedback relationship between estrogen and fetal hypothalamus-pituitary-adrenal (HPA) axis activity that is dependent upon PGHS activity in the fetal brain. The present study was designed to test the hypothesis that blockade of estrogen receptors in the fetal brain decrease PGHS-2 expression and reduces fetal HPA axis activity.
Conclusion
We conclude that PGHS-2 expression in the late-gestation fetal brain is in part stimulated by circulating estrogens in fetal plasma. Blockade of CNS estrogen receptors reduces preparturient plasma concentrations of POMC, but does not reduce fetal HPA axis activity in 130-134 day fetal sheep.
Methods
In study 1, six time-dated pregnant ewes with chronically-catheterized twin fetuses were used. In each pregnancy, one twin was treated intracerebroventricularly (icv) with the estrogen receptor antagonist ICI 182,780 (25 microg/day; n = 6) while the other twin served as an age-matched control. In study 2, plasma samples were drawn from 10 singleton chronically-catheterized fetuses on alternating days until the time of spontaneous parturition.
Results
ICI infusion caused significantly decreased PGHS-2 mRNA abundance in fetal central nervous system and pituitary, with the greatest decreases occurring in hippocampus and pituitary. There were no statistically significant changes in PGHS-1 mRNA. ICI infusion did not significantly change fetal plasma concentrations of pro-opiomelanocortin (POMC), ACTH, or cortisol in fetuses 130-134 days ges- tation (study 1) but did decrease the preparturient rise in plasma pro-opiomelanocortin concentrations in study 2.