Cloning of a novel receptor expressed in rat prostate and ovary.
TLDR
It is concluded that clone 29 cDNA encodes a novel rat ER, which is suggested be named rat ERbeta to distinguish it from the previously cloned ER (ERalpha) from rat uterus.Abstract:
We have cloned a novel member of the nuclear receptor superfamily. The cDNA of clone 29 was isolated from a rat prostate cDNA library and it encodes a protein of 485 amino acid residues with a calculated molecular weight of 54.2 kDa. Clone 29 protein is unique in that it is highly homologous to the rat estrogen receptor (ER) protein, particularly in the DNA-binding domain (95%) and in the C-terminal ligand-binding domain (55%). Expression of clone 29 in rat tissues was investigated by in situ hybridization and prominent expression was found in prostate and ovary. In the prostate clone 29 is expressed in the epithelial cells of the secretory alveoli, whereas in the ovary the granuloma cells in primary, secondary, and mature follicles showed expression of clone 29. Saturation ligand-binding analysis of in vitro synthesized clone 29 protein revealed a single binding component for 17beta-estradiol (E2) with high affinity (Kd= 0.6 nM). In ligand-competition experiments the binding affinity decreased in the order E2 > diethylstilbestrol > estriol > estrone > 5alpha-androstane-3beta,17beta-diol >> testosterone = progesterone = corticosterone = 5alpha-androstane-3alpha,17beta-diol. In cotransfection experiments of Chinese hamster ovary cells with a clone 29 expression vector and an estrogen-regulated reporter gene, maximal stimulation (about 3-fold) of reporter gene activity was found during incubation with 10 nM of E2. Neither progesterone, testosterone, dexamethasone, thyroid hormone, all-trans-retinoic acid, nor 5alpha-androstane-3alpha,I7beta-diol could stimulate reporter gene activity, whereas estrone and 5alpha-androstane-3beta,17beta-diol did. We conclude that clone 29 cDNA encodes a novel rat ER, which we suggest be named rat ERbeta to distinguish it from the previously cloned ER (ERalpha) from rat uterus.read more
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Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta
George G.J.M. Kuiper,Bo Carlsson,Kaj Grandien,Eva Enmark,Johan Häggblad,Stefan K. Nilsson,Jan-Åke Gustafsson +6 more
TL;DR: The messenger RNA expression of both ER subtypes in rat tissues by RT-PCR is investigated and the ligand binding specificity of the ER sub types is compared, revealing a single binding component for 16β-estradiol with high affinity.
Journal ArticleDOI
Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta.
George G. J. M. Kuiper,J.G. Lemmen,Bo Carlsson,J. Christopher Corton,Stephen Safe,Paul T. van der Saag,Bart van der Burg,Jan-Åke Gustafsson +7 more
TL;DR: The estrogenic activity of environmental chemicals and phytoestrogens in competition binding assays with ERα or ERβ protein, and in a transient gene expression assay using cells in which an acute estrogenic response is created by cotransfecting cultures with recombinant human ERβ complementary DNA (cDNA) in the presence of an estrogen-dependent reporter plasmid are investigated.
Journal ArticleDOI
The protective effects of estrogen on the cardiovascular system
TL;DR: Estrogen has direct and indirect effects on the cardiovascular system that are mediated by the estrogen receptors ER-alpha and ER-beta, and indirectly influences serum lipoprotein and triglyceride profiles, and the expression of coagulant and fibrinolytic proteins.
Journal ArticleDOI
Comparative distribution of estrogen receptor-alpha and -beta mRNA in the rat central nervous system.
TL;DR: Comparing the distribution of the classical and novel forms of ER mRNA‐expressing neurons in the central nervous system (CNS) of the rat with in situ hybridization histochemistry provides evidence that the region‐specific expression of ER‐α, ER‐β, or both may be important in determining the physiological responses of neuronal populations to estrogen action.
PatentDOI
DIFFERENTIAL LIGAND ACTIVATION OF ESTROGEN RECEPTORS ER$g(a) AND ER$g(b) AT AP1 SITES
Peter J. Kushner,Jan-Ake Gustafsson,George G.J.M. Kuiper,Stefan K. Nilsson,Kolja Paech,Thomas S. Scanlan,Paul W. Webb +6 more
TL;DR: In this article, a cell comprising an estrogen receptor beta (ER beta ), AP1 proteins, and a construct comprising a promoter comprising an AP1 site which regulates expression of a first reporter gene is contacted with the test compound and changes in expression levels of the reporter gene are detected indicating whether the test compounds activate transcription, inactivate transcription or have no effect at the AP1 sites.
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