Cerebral hypoperfusion increases estrogen receptor abundance in the ovine fetal brain and pituitary

Estrogen is an important component of fetal neuroendocrine function in late-gestation fetal sheep; however, little is known about the regulation of estrogen receptor abundance in the brain and pituitary of fetuses. The present study was performed to test the hypotheses that estrogen receptor abundance in the fetal brain and pituitary are influenced by circulating estradiol concentrations and that they are acutely regulated after cerebral hypoperfusion.

We studied 16 time-dated fetal sheep (124-128 days gestation) that were chronically catheterized and instrumented at least 5 days before study. Four groups (n = 4 each) were studied in which fetuses received estradiol (0.25 mg/day, producing physiological increases in fetal plasma estradiol concentrations) or placebo implants, and in which fetuses received a 10-min period of brachiocephalic occlusion (BCO) or sham-BCO. One hour after BCO or sham-BCO, fetuses were euthanized and tissues rapidly removed for analysis of estrogen receptors (ER)-alpha and -beta at the mRNA and protein levels.

Both BCO and estradiol treatment were effective in changing ER expression, although the effects were region-specific. BCO dramatically increased ER-alpha in the pituitary and both ER-alpha and ER-beta in the brainstem, while decreasing ER-alpha expression in the hypothalamus. Estradiol treatment decreased ER-alpha expression in the hypothalamus, whereas it increased ER-alpha expression in the brainstem, cerebral cortex and hippocampus.

We conclude that the expression of ER-alpha and ER-beta in the brain and pituitary of fetal sheep are influenced by circulating estrogen concentrations and acutely regulated in response to cerebral hypoperfusion.