Remodeling the estrogen receptor model

doi:10.1016/0303-7207(84)90079-0

Molecular and Cellular Endocrinology

Volume 36, Issues 1–2, June 1984, Pages 11-15

https://doi.org/10.1016/0303-7207(84)90079-0 Get rights and content

Abstract

The estrogen receptor model has revised to make it compatible with new data on subcellular localization of the receptor and physical characteristics of solubilized versus immobilized receptors. Our current model suggests that receptors, with or without bound estrogen, are present in the nuclear fraction. Furthermore, the receptor behaves as if it were immobilized or bound to some nuclear constituent at all times. Thus, the association of the estrogen-free receptor (unbound receptor) to a target site in the nucleus is considered to be the critical event in defining the nature of the response to estrogenic hormones.

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Cited by (125)

ERα and STAT5a cross-talk: Interaction through C-terminal portions of the proteins decreases STAT5a phosphorylation, nuclear translocation and DNA-binding
2004, FEBS Letters
Citation Excerpt :
Interestingly, the nucleus ERα level remained the same in cells expressing only ERα or co-expressing ERα and STAT5a (Fig. 4C, lower panel). This could be due to the fact that ER, unlike other steroid hormone receptors, is predominantly a nuclear protein regardless of whether or not it is complexed with the ligand [3,16]. Since both E2 and PRL play crucial roles in mammary gland development, differentiation and tumorigenesis, it would be revealing to see whether the ER–STAT5 cross-talk actually takes place in cells of mammary gland origin.
Cross-talk between ERα and STAT5a was demonstrated to mediate through a direct physical association between the two proteins. By GST pull-down assays and functional assays with various constructs of ERα and STAT5a, it was shown that the C-termini of these two proteins were mainly responsible for this interaction. Furthermore, the interaction between ERα and STAT5a was demonstrated to give rise to functional changes in their signaling events. In cell transfection studies, it was shown that ERα activation could attenuate PRLR signaling through STAT5a. This ERα-mediated attenuation of PRLR signaling was substantiated by observed decreases in the phosphorylation of JAK2 and STAT5a, reduced translocation of STAT5a into the nucleus, and reduced binding of STAT5a onto a GAS-containing nucleotide. Apart from transfected cells, the interaction between ERα and STAT5a could also be observed in established breast cancer cell lines of MCF-7 and T-47D in co-immunoprecipitation studies. However, the functional consequence of the interaction in these cancer cells was very different from the transfected HEK293 cells. ER activation could lead to potentiation of PRLR signaling in MCF-7 cells but not in T-47D cells. Conversely, in both MCF-7 and T-47D cells, PRLR activation could lead to attenuation of ER signaling. These data serve to elucidate the mechanisms underlying the ERα–STAT5a cross-talk and in demonstrating that the functional consequence of this cross-talk depends on the precise milieus of the intracellular environment.
Differential expression of estrogen receptor beta splice variants in rat brain: Identification and characterization of a novel variant missing exon 4
2000, Molecular Brain Research
Estrogen receptor beta (ER-β) mRNA is found in abundance in rat brain. The distribution of ER-β mRNA in brain differs from that of ER-α suggesting they subserve different functions. ER-β mRNA has been reported to be variably spliced, in contrast to ER-α, resulting in numerous isoforms that possess different functional properties. The present study was undertaken to determine whether the isoforms of ER-β mRNA are differentially distributed in different brain regions. In order to assess the range of transcript forms expressed in various brain regions in the same assay, a micropunch dissection technique was combined with semiquantitative RT-PCR. The relative abundance of each ER-β isoform (β1>β2>β1δ3>β2δ3) was similar in all ER-β positive brain regions with the exception of the hippocampus, which contained low levels of most isoforms and a fifth ER-β isoform, which we are calling ER-β1δ4. Based on its sequence, ER-β1δ4 encodes an ER-β that is missing exon 4. Initial characterization studies of this showed that it did not bind estrogen, and that, unlike ER-β1, it localized to the cytoplasm when expressed in cultured cells. The distribution of ER-β1δ4 was different from that of the other isoforms in that it was expressed at high levels in the hippocampus, where the other isoforms were low, and that it was nearly undetectable in the brain regions that expressed the highest levels of the other ER-β splice variants. These data suggest that a highly complex pattern of estrogen signaling can occur in a region specific manner in the rat brain.
Selective oestrogen receptor modulationmolecular pharmacology for the millennium
1999, European Journal of Cancer
Selective oestrogen receptor modulationmolecular pharmacology for the millennium
1999, European Journal of Cancer
Estrogen-receptor occurrence in the female mouse brain: Effects of maternal experience, ovariectomy, estrogen and anosmia
1994, Journal of Physiology - Paris
Maternal behavior (ultrasound-induced pup-searching and retrieving) was studied in eight groups of female house mice with various hormonal backgrounds, experience with pups and function of the olfactory system. In their brains, estrogen receptor immunoreactive (ER-IR) cells were localized and quantified. All animals of all groups had ER-IR cells in a ‘reliable subset’ of brain areas, the medial preoptic area (MPOA) and ventromedial (VMH) and arcuate nucleus (ARH) of the hypothalamus. In another subset of brain areas, the anterior hypothalamic area (AHA) and cortical (CA) and medial (MA) amygdaloid nucleus, ER-IR cells can be expected in at least some animals of all experimental groups (‘expected subset’). In a variable subset of additional brain areas (bed nucleus of the stria terminalis, BNST; suprachiasmatic nucleus, SC; lateral septal nuclei, LS; paraventricular nucleus of the hypothalamus, PVH; entorhinal and piriform cortex, ENT, PIR; subiculum, SUB; hippocampus, HPC; periventricular gray of the midbrain, PVG), ER-IR cells occurred only in some animals of some groups. Numbers of ER-IR cells in a given brain area, volumes occupied by these cells, and cell densities varied considerably among the groups. A covariation of cell counts and volumes was significant for most brain areas indicating that increases of numbers of ER-IR cells relate mainly to volume increases within a given brain area. Experience with pups correlated with an increase of ER presence in the AHA, VMH, ENT, PIR, SUB, HPC and PVG, however, only in the presence of estrogen. Estrogen and pup-experience together led to an increased ER presence in mainly the VMH, ENT and PIR, however, only in females with intact olfaction. Full maternal behavior (retrieving, ultrasound recognition) occurred after the high pregnancy- or experience-induced ER content was reduced to lower levels. The ER occureence in lactating and experienced virgin females differed, however, in the AHA, BNST, SC, PVH, ENT, PIR, SUB, HPC and PVG showing that the maintenance of maternal behavior can run under different profiles of ER content in the brain. Ovariectomy and/or prolonged high blood-estrogen levels correlated significantly with decreased levels of ER-IR cells in most brain areas which could not be increased by pup-experience.
Novel interactions between ERα-36 and STAT3 mediate breast cancer cell migration
2019, Cell Communication and Signaling

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ReviewRemodeling the estrogen receptor model

Abstract

Cell

Recent Progr. Hormone Res.

Biochem. Biophys. Res. Commun.

Recent Progr. Hormone Res.

Vitamins Hormones

Cell

Cell

J. Biol. Chem.

J. Biol. Chem.

Recent Progr. Hormone Res.

J. Biol. Chem.

Review
Remodeling the estrogen receptor model