Progestin receptor expression in the developing rat brain depends upon activation of estrogen receptor α and not estrogen receptor β

Perinatal 17 beta-estradiol (E2) rapidly and markedly affects the morphological and neurochemical organization of the vertebrate brain. For instance, the sex difference in perinatal progestin receptor (PR) immunoreactivity in the medial preoptic nucleus (MPN) of. the rat brain is due to the intracellular conversion of testosterone into E2 in males. Neonatal alpha-fetoprotein prevents circulating estrogens from accessing the brain, therefore, to overcome alpha-fetoprotein sequestration of E2, estrogen replacement studies during development have used natural and synthetic estrogen dosages in the milligram to microgram range. These levels could be considered as supraphysiological. Moreover, it is not clear through which ER subtype E2 acts to induce PR expression in the neonatal rat MPN because E2 binds similarly to estrogen receptor (ER)alpha and ER beta. Consequently, we investigated whether nanogram levels of E2 affected PR protein and mRNA levels in the neonatal MPN. Furthermore, propylpyrazole-triol (PPT), a highly selective agonist for ER alpha, and diarylpropionitrile (DPN), a highly selective agonist for ER beta, were used to deter-mine if E2-dependent PR expression in the neonatal rat is mediated through ER alpha and/or ER beta. Immunocytochemistry and quantitative real-time RT-PCR determined that as little as 100 ng E2 significantly induced PR protein and mRNA in the female and neonatally castrated male MPN on PN 4, indicating that the neonatal rat brain is highly sensitive to circulating estrogens. PPT, but not DPN, induced PR expression in the neonatal MPN and arcuate nucleus (Arc), demonstrating that PR expression in the neonatal rat brain depends solely on E2 activated ER alpha. In the lateral bed nucleus of the stria terminalis (BSTL), neither PPT nor DPN affected PR expression, suggesting the presence of a gonadal hormone-independent PR regulatory mechanism. (c) 2006 Elsevier B.V. All rights reserved.