Blockade of estrogen action upregulates estrogen receptor-alpha 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.


CONCLUSIONS
Expression of ER-alpha is influenced by endogenous estrogens in the ovine fetal brain.
Schaub
Christine E
CE
Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, FL 32610-0274, USA.
Wood
Charles E
CE
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D047109:Fetal Development / Q000187:drug effects; D005333:Fetus / Q000187:drug effects / Q000196:embryology; D000077267:Fulvestrant; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D012756:Sheep
D004965:Estrogen Antagonists; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D000077267:Fulvestrant; D004958:Estradiol