Vincent Giguère

Bio: Vincent Giguère is an academic researcher from McGill University. The author has contributed to research in topics: Nuclear receptor & Retinoic acid receptor. The author has an hindex of 82, co-authored 227 publications receiving 27481 citations. Previous affiliations of Vincent Giguère include University of Toronto & École normale supérieure de Lyon.

Identification of a receptor for the morphogen retinoic acid.

Abstract: Analysis of complementary DNA encoding a novel gene product reveals striking similarity to the steroid and thyroid hormone receptors. Binding and transcription activational studies show it to be a receptor for the vitamin A-related morphogen retinoic acid.

Cloning, chromosomal localization, and functional analysis of the murine estrogen receptor β

Abstract: Estrogen receptor β (ERβ) is a novel steroid receptor that is expressed in rat prostate and ovary We have cloned the mouse homolog of ERβ and mapped the gene, designated Estrb, to the central region of chromosome 12 The cDNA encodes a protein of 485 amino acids that shares, respectively, 97% and 60% identity with the DNA- and ligand-binding domains of mouse (m) ERα Mouse ERβ binds to an inverted repeat spaced by three nucleotides in a gel mobility shift assay and transactivates promoters containing synthetic or natural estrogen response elements in an estradiol (E2)-dependent manner Scatchard analysis indicates that mERβ has slightly lower affinity for E2 [dissociation constant (Kd) = 05 nm] when compared with mERα (Kd = 02 nm) Antiestrogens, including 4-hydroxytamoxifen (OHT), ICI 182,780, and a novel compound, EM-800, inhibit E2-dependent transactivation efficiently However, while OHT displays partial agonistic activity with ERα on a basal promoter linked to estrogen response elements in Cos-1 c

Orphan nuclear receptors: from gene to function.

Abstract: I. Introduction II. Nuclear Receptors: General Concepts A. Anatomy of nuclear receptors B. Mechanisms of action III. Orphan Nuclear Receptors A. Definition B. Nomenclature C. Structural and functional diversity IV. Novel Hormone Response Systems: RXR and Its Heterodimeric Partners A. RXR: rexinoids B. PPAR: multiple ligands, multiple functions C. PXR: pregnanes, xenobiotic compounds, and benzoate derivatives D. CAR (constitutive androstane receptor): androstanes and phenobarbital E. LXR: control of cholesterol metabolism by oxysterols F. FXR: bile acids receptor V. Orphans in Search of a Home A. HNF4: diabetes and possible regulation by acyl-coenzyme A (CoA) thioesters B. FTZ-F1: steroidogenesis and sexual development C. Rev-Erb: singular members of the superfamily D. ROR: neuron development and T cell selection E. TR2: the testis receptors F. TLX: forebrain development G. COUP-TF: neurogenesis, angiogenesis, and heart development H. ERR: placenta development and control of lipid metabolism I. NGFI-B: hyp...

The steroid and thyroid hormone receptor superfamily

Abstract: Analyses of steroid receptors are important for understanding molecular details of transcriptional control, as well as providing insight as to how an individual transacting factor contributes to cell identity and function. These studies have led to the identification of a superfamily of regulatory proteins that include receptors for thyroid hormone and the vertebrate morphogen retinoic acid. Although animals employ complex and often distinct ways to control their physiology and development, the discovery of receptor-related molecules in a wide range of species suggests that mechanisms underlying morphogenesis and homeostasis may be more ubiquitous than previously expected.

Cloning of a novel receptor expressed in rat prostate and ovary.

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.

Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta.

Abstract: The rat, mouse and human estrogen receptor (ER) exists as two subtypes, ER alpha and ER beta, which differ in the C-terminal ligand-binding domain and in the N-terminal transactivation domain. In this study, we investigated the estrogenic activity of environmental chemicals and phytoestrogens in competition binding assays with ER alpha or ER beta protein, and in a transient gene expression assay using cells in which an acute estrogenic response is created by cotransfecting cultures with recombinant human ER alpha or ER beta complementary DNA (cDNA) in the presence of an estrogen-dependent reporter plasmid. Saturation ligand-binding analysis of human ER alpha and ER beta protein revealed a single binding component for [3H]-17beta-estradiol (E2) with high affinity [dissociation constant (Kd) = 0.05 - 0.1 nM]. All environmental estrogenic chemicals [polychlorinated hydroxybiphenyls, dichlorodiphenyltrichloroethane (DDT) and derivatives, alkylphenols, bisphenol A, methoxychlor and chlordecone] compete with E2 for binding to both ER subtypes with a similar preference and degree. In most instances the relative binding affinities (RBA) are at least 1000-fold lower than that of E2. Some phytoestrogens such as coumestrol, genistein, apigenin, naringenin, and kaempferol compete stronger with E2 for binding to ER beta than to ER alpha. Estrogenic chemicals, as for instance nonylphenol, bisphenol A, o, p'-DDT and 2',4',6'-trichloro-4-biphenylol stimulate the transcriptional activity of ER alpha and ER beta at concentrations of 100-1000 nM. Phytoestrogens, including genistein, coumestrol and zearalenone stimulate the transcriptional activity of both ER subtypes at concentrations of 1-10 nM. The ranking of the estrogenic potency of phytoestrogens for both ER subtypes in the transactivation assay is different; that is, E2 >> zearalenone = coumestrol > genistein > daidzein > apigenin = phloretin > biochanin A = kaempferol = naringenin > formononetin = ipriflavone = quercetin = chrysin for ER alpha and E2 >> genistein = coumestrol > zearalenone > daidzein > biochanin A = apigenin = kaempferol = naringenin > phloretin = quercetin = ipriflavone = formononetin = chrysin for ER beta. Antiestrogenic activity of the phytoestrogens could not be detected, except for zearalenone which is a full agonist for ER alpha and a mixed agonist-antagonist for ER beta. In summary, while the estrogenic potency of industrial-derived estrogenic chemicals is very limited, the estrogenic potency of phytoestrogens is significant, especially for ER beta, and they may trigger many of the biological responses that are evoked by the physiological estrogens.