Blockade of Estrogen Action Upregulates Estrogen Receptor-α mRNA in the Fetal Brain

BACKGROUND Fetal neuroendocrine maturation in late gestation is critical for maintenance of fetal homeostasis, growth, and readiness for birth. Sheep express estrogen receptors (ERs) in various brain regions. However, little is known about the regulation of ER-alpha and ER-beta in the ovine brain prenatally. OBJECTIVE The present study was designed to test the hypothesis that the expression of ER is influenced by circulating estrogens in the late-gestation sheep fetus. METHODS Six chronically-catheterized twin fetal sheep were treated with vehicle or the ER blocker ICI 182,780 i.c.v. (0.25 microg/day). Fetuses were sacrificed 6-14 days after surgery and start of infusion. Brain regions were rapidly isolated and snap-frozen for later extraction of mRNA and protein. ER-alpha and ER-beta mRNA was measured using real-time PCR and protein was measured using Western blot. RESULTS Treatment with ICI 182,780 increased ER-alpha mRNA, especially in cerebellum and hippocampus. There were no changes in ER-alpha protein and no changes in ER-beta at either the mRNA or protein level. CONCLUSION Expression of ER-alpha is influenced by endogenous estrogens in the ovine fetal brain.