Project description: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.
Project description:In the fetal sheep during late gestation sulfoconjugated estrogens in plasma reach a concentration 40-100 times greater than unconjugated estrogens. The objective of the present study was to determine the genomics of estradiol-3-sulfate (E2S) action in the fetal brain. The hypothesis was that E2S stimulates genes involved in the neuroendocrine pathways in the hypothalamus that direct or facilitate fetal development at the end of gestation. Four sets of chronically-catheterized ovine twin fetuses were studied (gestational age: 120-127 days gestation) with one infused with E2S intracerebroventricularly (1 mg/day) and the other remained untreated (control). After euthanasia, mRNA samples were extracted from the 8 hypothalami, corresponding to the four treatment and four control fetuses. Microarray analysis was performed following the Agilent protocol for 1-color 8x15 microarrays, designed for Ovis aries.
