BIDIRECTIONAL TRANSCRIPTION REGULATION OF GLIAL FIBRILLARY ACIDIC PROTEIN BY ESTRADIOL IN-VIVO AND IN-VITRO

Glial fibrillary acidic protein (GFAP) expression shows cyclic variati on in the rat hypothalamus and hippocampus during the normal estrous c ycle. To elucidate the role of transcription in the regulation of GFAP , we examined levels of GFAP intron 1 by in situ hybridization in the hypothalamus and hippocampus of normal, cycling rats. On the afternoon of proestrus, when plasma estradiol levels are highest, GFAP transcri ption and messenger RNA were both increased in the arcuate nucleus of the hypothalamus and decreased in the outer molecular layer of the den tate gyrus. In the hilus of the hippocampus, neither GFAP transcriptio n nor messenger RNA changed during the estrous cycle. In vitro, astroc ytes showed bidirectional responses, such that estradiol treatment inc reased GFAP transcription in monotypic astrocytic cultures but decreas ed GFAP transcription in astrocytes cocultured with neurons. The funct ionality of an estrogen response element in the 5'-upstream region of the GFAP promoter was established by site-directed mutagenesis and bin ding of human recombinant estrogen receptor in gel shift assays. We co nclude that estrogen may act directly upon astrocytes by estrogen rece ptor binding, and that the direction of the transcriptional response i s influenced by astrocyte-neuron interactions.