Estradiol and ICI 182,780 infusions induce similar transcriptomic response in late gestation fetal hypothalamus

Estradiol plays a critical role stimulating the fetal hypothalamus-pituitary-adrenal axis at the end of gestation. Estradiol action is mediated through nuclear and membrane receptors that can be modulated by ICI 182,780, a pure anti-estrogen compound. The objective of this study was to evaluate the transcriptomics of estradiol and ICI 182,780, testing the hypothesis that ICI 182,780 blocks the action of estradiol in the fetal hypothalamus. However, we found that a short term (48 hrs) infusion with ICI 182,780 induces a similar transcriptomic response than estradiol infusion in the late gestation ovine fetal hypothalamus, being more evident with higher doses of ICI 182,780. These results suggest that ICI 182,780 is primarily an agonist of estradiol in the developing brain. For direct TCS exposure, chronically catheterized late gestation fetal sheep were infused with vehicle (n=4) or TCS (250 μg/day; n=4) iv. For indirect TCS exposure, TCS (100 μg/kg/day; n=3) or vehicle (n=3) was infused into the maternal circulation. Fetal hypothalami were collected after 2 days of infusion, and gene expression was measured using Agilent 15k ovine microarrays.