Rh. Price et al., Differential expression of estrogen receptor beta splice variants in rat brain: identification and characterization of a novel variant missing exon 4, MOL BRAIN R, 80(2), 2000, pp. 260-268
Estrogen receptor beta (ER-beta) mRNA is found in abundance in rat brain. T
he distribution of ER-beta mRNA in brain differs from that of ER-alpha sugg
esting they subserve different functions. ER-beta mRNA has been reported to
be variably spliced, in contrast to ER-alpha, resulting in numerous isofor
ms that possess different functional properties. The present study was unde
rtaken to determine whether the isoforms of ER-beta mRNA are differentially
distributed in different brain regions. In order to assess the range of tr
anscript forms expressed in various brain regions in the same assay, a micr
opunch dissection technique was combined with semiquantitative RT-PCR, The
relative abundance of each ER-beta isoform (beta 1>beta 2>beta 1 delta 3>be
ta 2 delta 3) was similar in all ER-beta positive brain regions with the ex
ception of the hippocampus, which contained low levels of most isoforms and
a fifth ER-beta isoform, which we are calling ER-beta 1 delta 4, Based on
its sequence, ER-beta 1 delta 4 encodes an ER-beta that is missing exon 4.
Initial characterization studies of this showed that it did not bind estrog
en, and that, unlike ER-beta 1, it localized to the cytoplasm when expresse
d in cultured cells. The distribution of ER-beta 1 delta 4 was different fr
om that of the other isoforms in that it was expressed at high levels in th
e hippocampus, where the other isoforms were low, and that it was nearly un
detectable in the brain regions that expressed the highest levels of the ot
her ER-beta splice variants. These data suggest that a highly complex patte
rn of estrogen signaling can occur in a region specific manner in the rat b
rain. (C) 2000 Elsevier Science B.V. All rights reserved.