Download PDF
Horm Metab Res 2006; 38(4): 269-278
DOI: 10.1055/s-2006-925349
Review
© Georg Thieme Verlag KG Stuttgart · New York

The Retinol-binding Protein System: A Potential Paradigm for Steroid-binding Globulins?

C.  Redondo1 , B.  J.  Burke1 , J.  B. C.  Findlay1
  • 1 Department of Biochemistry and Microbiology, University of Leeds, United Kingdom
Further Information

Publication History

Received 23 September 2005

Accepted after revision 10 November 2005

Publication Date:
15 May 2006 (online)

Also available at
    Permissions and Reprints

Abstract

Retinol (vitamin A) is an example of a small molecule that is essential for higher organisms; its utilisation has been involved in the evolution of a number of proteins. In mammalian species, retinol is obtained from the diet and controls the release of its binding protein from hepatocytes into the blood stream. Subsequent influx into cells under normal situations usually involves a specific membrane-bound receptor for retinol-binding protein, which facilitates the uptake of retinol alone or bound to its carrier. This specific receptor has not yet been identified, but a receptor for a related lipocalin has been cloned. It represents a relatively new family, and there are a number of related genes in various eukaryotic genomes, suggesting that the system is very widespread in multicellular organisms. Its significance has been highlighted recently by the suggestion that retinol-binding protein, through its receptor, may play a major role in type 2 diabetes, perhaps the greatest scourge of modern society. This system may provide a new paradigm in mammalian biology, another example of which may exist in the processes responsible for steroid handling. This review outlines the characteristics of retinol utilisation in mammalian species, focusing primarily on the uptake system.

Key words

Lipocalin - receptor - transport - vitamin A - conformations

References

  • 1 Watson C S, Gametchu B. Proteins of multiple classes may participate in nongenomic steroid actions.  Exp Biol Med (Maywood). 2003;  228(11) 1272-1281
    PubMedGoogle Scholar
  • 2 de Wolf F A, Brett G M. Ligand-binding proteins: their potential for application in systems for controlled delivery and uptake of ligands.  Pharmacol Rev. 2000;  52(2) 207-236
    PubMedGoogle Scholar
  • 3 Gottesman M E, Quadro L, Blaner W S. Studies of vitamin A metabolism in mouse model systems.  Bioessays. 2001;  23(5) 409-419
    CrossrefPubMedGoogle Scholar
  • 4 Noy N, Xu Z J. Interactions of retinol with binding proteins: implications for the mechanism of uptake by cells.  Biochemistry. 1990;  29(16) 3878-3883
    CrossrefPubMedGoogle Scholar
  • 5 Sivaprasadarao A, Findlay J B. The interaction of retinol-binding protein with its plasma-membrane receptor.  Biochem J. 1988;  255(2) 561-569
    PubMedGoogle Scholar
  • 6 Sivaprasadarao A, Findlay J B. The mechanism of uptake of retinol by plasma-membrane vesicles.  Biochem J. 1988;  255(2) 571-579
    PubMedGoogle Scholar
  • 7 Shingleton J L, Skinner M K, Ong D E. Characteristics of retinol accumulation from serum retinol-binding protein by cultured Sertoli cells.  Biochemistry. 1989;  28 9641-9647
    CrossrefPubMedGoogle Scholar
  • 8 Senoo H, Smeland S, Malaba L, Bjerknes T, Stang E, Roos N, Berg T, Norum K R, Blomhoff R. Transfer of retinol-binding protein from HepG2 human hepatoma cells to co-cultured rat stellate cells.  Proc Natl Acad Sci USA. 1993;  90 3616-3620
    PubMedGoogle Scholar
  • 9 Davis J T, Ong D E. Retinol processing by the peritubular cell from rat testis.  Biol Reprod. 1995;  52 356-364
    CrossrefPubMedGoogle Scholar
  • 10 Pfeffer B A, Clark V M, Flannery J G, Bok D. Membrane receptors for retinol-binding protein in cultured human retinal pigment epithelium. Invest.  Ophthalmol Vis Sci. 1986;  27 1031-1040
    PubMedGoogle Scholar
  • 11 Bavik C O, Eriksson U, Allen R A, Peterson P A. Identification and partial characterization of a retinal pigment epithelial membrane receptor for plasma retinol-binding protein.  J Biol Chem. 1991;  266 14 978-14 985
    PubMedGoogle Scholar
  • 12 Eriksson U, Hansson E, Nilsson M, Jonsson K H, Sundelin J, Peterson P A. Increased levels of several retinoid binding proteins resulting from retinoic acid-induced differentiation of F9 cells.  Cancer Res. 1986;  46 717-722
    PubMedGoogle Scholar
  • 13 MacDonald P N, Bok D, Ong D E. Localization of cellular retinol-binding protein and retinol-binding protein in cells comprising the blood-brain barrier of rat and human.  Proc Natl Acad Sci USA,. 1990;  87 4265-4269
    PubMedGoogle Scholar
  • 14 Nakhla A M, Leonard J, Hryb D J, Rosner W. Sex hormone-binding globulin receptor signal transduction proceeds via a G protein.  Steroids. 1999;  64 213-216
    CrossrefPubMedGoogle Scholar
  • 15 Maitra U S, Khan M S, Rosner W. Corticosteroid-binding globulin receptor of the rat hepatic membrane: solubilization, partial characterization, and the effect of steroids on binding.  Endocrinol. 1993;  133 1817-1822
    CrossrefPubMedGoogle Scholar
  • 16 Yang Q, Graham T E, Mody N, Preitner F, Peroni O F, Zabolotny J M, Kotani K, Quadro L, Kahn B B. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes.  Nature. 2005;  436(7049) 356-562
    CrossrefPubMedGoogle Scholar
  • 17 Heller J. Transport of retinol to ocular tissues. An overview.  World Rev Nutr Diet. 1978;  31 42-44
    PubMedGoogle Scholar
  • 18 Futterman S, Heller J. The enhancement of fluorescence and the decreased susceptibility to enzymatic oxidation of retinol complexed with bovine serum albumin, β -lactoglobulin, and the retinol-binding protein of human plasma.  J Biol Chem. 1972;  247(16) 5168-5172
    PubMedGoogle Scholar
  • 19 Horwitz J, Heller J. Interactions of all-trans, 9-, 11-, and 13-cis-retinal, all-trans-retinyl acetate, and retinoic acid with human retinol-binding protein and prealbumin.  J Biol Chem. 1973;  248(18) 6317-6324
    PubMedGoogle Scholar
  • 20 Heller J, Horwitz J. Conformational changes following interaction between retinol isomers and human retinol-binding protein and between the retinol-binding protein and prealbumin.  J Biol Chem. 1973;  248(18) 6308-6316
    PubMedGoogle Scholar
  • 21 Heller J, Horwitz J. The binding stoichiometry of human plasma retinol-binding protein to prealbumin.  J Biol Chem. 1974;  249(18) 5933-5938
    PubMedGoogle Scholar
  • 22 Heller J, Horwitz J. Interactions of retinol-binding protein with various chromophores and with thyroxine-binding protein. A model for visual pigments.  Exp Eye Res. 1974;  18(1) 41-49
    CrossrefPubMedGoogle Scholar
  • 23 Bok D, Heller J. Transport of retinol from the blood to the retina: an autoradiographic study of the pigment epithelial cell surface receptor for plasma retinol-binding protein.  Exp Eye Res. 1976;  22(5) 395-402
    CrossrefPubMedGoogle Scholar
  • 24 Chen C C, Heller J. Uptake of retinol and retinoic acid from serum retinol-binding protein by retinal pigment epithelial cells.  J Biol Chem. 1977;  252(15) 5216-5221
    PubMedGoogle Scholar
  • 25 Ong D E. Cellular transport, and metabolism of vitamin A: role of the cellular retinoid-binding proteins.  Nutr Rev. 1994;  52 24-31
    PubMedGoogle Scholar
  • 26 Ette S I, Basu T K, Dickerson J WT. Short-term effect of zinc sulfate on plasma and hepatic concentrations of vitamins A and E in normal weanling rats.  Nutr Metab. 1979;  23 11-16
    PubMedGoogle Scholar
  • 27 Olson J A. Benefits and liabilities of vitamin A and carotenoids.  J Nutr. 1996;  126 (4 Suppl) 1208-1212
    PubMedGoogle Scholar
  • 28 Bonet M L, Ribot J, Felipe F, Palou A. Vitamin A and the regulation of fat reserves.  Cell Mol Life Sci. 2003;  60(7) 1311-1321
    CrossrefPubMedGoogle Scholar
  • 29 Tsutsumi C, Okuno M, Tannous L, Piantedosi R, Allan M, Goodman D S, Blaner W S. Retinoids and retinoid-binding protein expression in rat adipocytes.  J Biol Chem. 1992;  267(3) 1805-1810
    PubMedGoogle Scholar
  • 30 Harrison E H. Mechanisms of digestion and absorption of dietary vitamin A.  Annu Rev Nutr. 2005;  25 7-103
    PubMedGoogle Scholar
  • 31 Soprano D R, Blaner W S. Plasma retinol-binding protein. In: Sporn MB, Roberts AB, Goodman DS. (eds.) The retinoids: biology, chemistry and medicine. 2nd ed. New York; Raven Press 1994: 257-282
    Google Scholar
  • 32 Blomhoff R. Overview of vitamin A: metabolism and function. In: Blomhoff, R. (ed.) Vitamin A in health and disease. New York; Marcel Dekker 1994: 1-35
    Google Scholar
  • 33 Goodman D S. Plasma retinol-binding protein. In: Sporn, MB, Roberts, AB Goodman, DS (eds.) The Retinoids, vol. 2. 1984 New York; Academic Press 41-88
    Google Scholar
  • 34 Ingenbleek Y, Young V. Transthyretin (prealbumin) in health and disease: Nutritional implications.  Annual Review of Nutrition. 1994;  14 495-533
    CrossrefPubMedGoogle Scholar
  • 35 Bellovino D, Morimoto T, Tosetti F, Gaetani S. Retinol-binding protein and transthyretin are secreted as a complex formed in the endoplasmic reticulum in HepG2 human hepatocarcinoma cells.  Exp Cell Res. 1996;  222 77-83
    CrossrefPubMedGoogle Scholar
  • 36 Mehlus H, Nilsson T, Peterson P A, Rask L. Retinol-binding protein and transthyretin expressed in Hela cells form a complex in the endoplasmic reticulum both in the absence and in the presence of retinol.  Exp Cell Res. 1991;  197 119-124
    CrossrefPubMedGoogle Scholar
  • 37 Newcomer M E, Ong D E. Plasma retinol binding protein: structure and function of the prototypic lipocalin.  Biochim Biophys Acta. 2000;  1482(1 - 2) 57-64
    PubMedGoogle Scholar
  • 38 Sundaram M, Sivaprasadarao A, DeSousa M M, Findlay J B. The transfer of retinol from serum retinol-binding protein to cellular retinol-binding protein is mediated by a membrane receptor.  J Biol Chem. 1998;  273 3336-3342
    CrossrefPubMedGoogle Scholar
  • 39 Zanotti G, Marcello M, Malpeli G, Folli C, Sartori G, Berni R. Crystallographic studies on complexes between retinoids and plasma retinol-binding protein.  J Biol Chem. 1994;  269(47) 29 613-29 620
    PubMedGoogle Scholar
  • 40 Hathcock J N, Hattan D G, Jenkins M Y, McDonald J T, Sundaresan P R, Wilkening V L. Evaluation of vitamin A toxicity.  Am J Clin Nutr. 1990;  52 183-202
    PubMedGoogle Scholar
  • 41 Tanumihardjo S A. Functions and actions of retinoids and carotenoids: building the vision of James Allen Olson.  Am Soc Nutr Sci. 2004;  290S-293S
    PubMedGoogle Scholar
  • 42 Dixon J L, DS G oodman. Studies on the metabolism of retinol-binding protein by primary hepatocytes from retinol-deficient rats.  J Cell Physiol. 1987;  130 14-20
    CrossrefPubMedGoogle Scholar
  • 43 Perozzi G, Mengheri E, Colantuoni V, Gaetani S. Vitamin A intake and in vivo expression of the genes involved in retinol transport.  Eur J Biochem. 1991;  196 211-217
    CrossrefPubMedGoogle Scholar
  • 44 Christian P, West K P Jr. Interactions between zinc and vitamin A: an update.  Am J Clin Nutr. 1998;  68 435S-441S
    PubMedGoogle Scholar
  • 45 Kanai M, Raz A, Goodman D. Retinol binding protein: the transport protein for vitamin A in human plasma.  J Clin Invest. 1968;  47 2025-2044
    PubMedGoogle Scholar
  • 46 Newcomer M E, Ong D E. Plasma retinol binding protein: structure and function of the prototypic lipocalin.  Biochim Biophys Acta. 2000;  1482(1 - 2) 57-64
    PubMedGoogle Scholar
  • 47 Bellovino D, Apreda M, Gragnoli S, Massimi M, Gaetani S. Vitamin A transport: in vitro models for the study of RBP secretion.  Molecular Aspects of Medicine. 2003;  24 411-420
    CrossrefPubMedGoogle Scholar
  • 48 Newcomer M E, Jones T A, Aqvist J, Sundelin J, Eriksson U, Rask L, Peterson P A. The three-dimensional structure of retinol-binding protein.  EMBO J. 1984;  3(7) 1451-1454
    PubMedGoogle Scholar
  • 49 Cowan S W, Newcomer M E, Jones T A. Crystallographic refinement of human serum retinol binding protein at 2A resolution.  Proteins. 1990;  8(1) 44-61
    CrossrefPubMedGoogle Scholar
  • 50 Zanotti G, Ottonello S, Berni R, Monaco H L. Crystal structure of the trigonal form of human plasma retinol-binding protein at 2.5 A resolution.  J Mol Biol. 1993;  230(2) 613-624
    CrossrefPubMedGoogle Scholar
  • 51 Zanotti G, Berni R, Monaco H L. Crystal structure of liganded and unliganded forms of bovine plasma retinol-binding protein.  J Biol Chem. 1993;  268(15) 10 728-10 738
    PubMedGoogle Scholar
  • 52 Zanotti G, Panzalorto M, Marcato A, Malpeli G, Folli C, Berni R. Structure of pig plasma retinol-binding protein at 1.65 A resolution.  Acta Crystallogr D Biol Crystallogr. 1998;  54(Pt 5) 1049-1052
    CrossrefPubMedGoogle Scholar
  • 53 Zanotti G, Calderone V, Beda M, Malpeli G, Folli C, Berni R. Structure of chicken plasma retinol-binding protein.  Biochim Biophys Acta. 2001;  1550(1) 64-69
    PubMedGoogle Scholar
  • 54 Noy N, Slosberg E, Scarlata S. Interactions of retinol with binding proteins: studies with retinol-binding protein and with transthyretin.  Biochemistry. 1992;  31(45) 11 118-1124
    PubMedGoogle Scholar
  • 55 Sivaprasadarao A, Findlay J B. Structure-function studies on human retinol-binding protein using site-directed mutagenesis.  Biochem J. 1994;  300 437-442
    PubMedGoogle Scholar
  • 56 Newcomer M E. Retinoid-binding proteins: structural determinants important for function.  FASEB J. 1995;  9(2) 229-239
    PubMedGoogle Scholar
  • 57 Monaco H L. The transthyretin-retinol-binding protein complex.  Biochim Biophys Acta. 2000;  1482(1 - 2) 65-72
    PubMedGoogle Scholar
  • 58 Shidoji Y, Muto Y. Vitamin A transport in plasma of the non-mammalian vertebrates: isolation and partial characterisation of piscine retinol-binding-protein.  Journal of Lipid Research. 1977;  18 679-691
    PubMedGoogle Scholar
  • 59 Senoo H, Stang E, Nilsson A, Kindberg G M, Berg T, Roos N, Norum K R, Blomhoff R. Internalization of retinol-binding protein in parenchymal and stellate cells of rat liver.  J Lipid Res. 1990;  31(7) 1229-1239
    PubMedGoogle Scholar
  • 60 Matarese V, Lodish H F. Specific uptake of retinol-binding protein by variant F9 cell lines.  J Biol Chem. 1993;  268(25) 18 859-18 865
    PubMedGoogle Scholar
  • 61 Bavik C O, Busch C, Eriksson U. Characterization of a plasma retinol-binding protein membrane receptor expressed in the retinal pigment epithelium.  J Biol Chem. 1992;  267(32) 23 035-23 042
    PubMedGoogle Scholar
  • 62 Sivaprasadarao A, Boudjelal M, Findlay J B. Solubilization and purification of the retinol-binding protein receptor from human placental membranes.  Biochem J. 1994;  302( Pt 1) 245-251
    PubMedGoogle Scholar
  • 63 Sundaram M, van Aalten D M, Findlay J B, Sivaprasadarao A. The transfer of transthyretin and receptor-binding properties from the plasma retinol-binding protein to the epididymal retinoic acid-binding protein.  Biochem J. 2002;  362(Pt 2) 265-271
    CrossrefPubMedGoogle Scholar
  • 64 Piantedosi R, Ghyselinck N, Blaner W S, Vogel S. Cellular retinol-binding protein type III is needed for retinoid incorporation into milk.  J Biol Chem. 2005;  280(25) 24 286-24 292
    PubMedGoogle Scholar
  • 65 Folli C, Calderone V, Ramazzina I, Zanotti G, Berni R. Ligand binding and structural analysis of a human putative cellular retinol-binding protein.  J Biol Chem. 2002;  277(44) 41 970-41 977
    PubMedGoogle Scholar
  • 66 Matt N, Schmidt C K, Dupe V, Dennefeld C, Nau H, Chambon P, Mark M, Ghyselinck N B. Contribution of cellular retinol-binding protein type 1 to retinol metabolism during mouse development.  Dev Dyn. 2005;  233(1) 167-176
    CrossrefPubMedGoogle Scholar
  • 67 Noy N. Retinoid-binding proteins: mediators of retinoid action.  Biochem J. 2000;  348 (Pt 3) 481-495
    CrossrefPubMedGoogle Scholar
  • 68 Weiler R, Pottek M, Schultz K, Janssen-Bienhold U. Retinoic acid, a neuromodulator in the retina.  Prog Brain Res. 2001;  131 309-318
    PubMedGoogle Scholar
  • 69 Cowan S W, Newcomer M E, Jones T A. Crystallographic studies on a family of cellular lipophilic transport proteins. Refinement of P2 myelin protein and the structure determination and refinement of cellular retinol-binding protein in complex with all-trans-retinol.  J Mol Biol. 1993;  230(4) 1225-1246
    CrossrefPubMedGoogle Scholar
  • 70 Tosetti F, Ferrari N, Pfeffer U, Brigati C, Vidali G. Regulation of plasma retinol binding protein secretion in human HepG2 cells.  Exp Cell Res. 1992;  200 467-472
    CrossrefPubMedGoogle Scholar
  • 71 Bellovino D, Lanyau Y, Garaguso I, Amicone L, Cavallari C, Tripodi M, Gaetani S. MMH cells: An in vitro model for the study of retinol-binding protein secretion regulated by retinol.  J Cell Physiol. 1999;  181(1) 24-32
    CrossrefPubMedGoogle Scholar
  • 72 Quadro L, Blaner W S, Salchow D J, Vogel S, Piantedosi R, Gouras P, Freeman S, Cosma M P, Colantuoni V, Gottesman M E. Impaired retinal function and vitamin A availability in mice lacking retinol-binding protein.  EMBO J. 1999;  18(17) 4633-4644
    CrossrefPubMedGoogle Scholar
  • 73 Quadro L, Blaner W S, Hamberger L, van Gelder R N, Vogel S, Piantedosi R, Gorras P, Colantuoni V, Gottesman M E. Muscle expression of human retinol-binding protein (RBP). Suppression of the visual defect of RBP knockout mice.  J Biol Chem. 2002;  277(33) 30 191-30 197
    PubMedGoogle Scholar
  • 74 Quadro L, Hamberger L, Colantuoni V, Gottesman M E, Blaner W S. Understanding the physiological role of retinol-binding protein in vitamin A metabolism using transgenic and knockout mouse models.  Mol Aspects Med. 2003;  24(6) 421-430
    PubMedGoogle Scholar
  • 75 Seeliger M W, Biesalski H K, Wissinger B, Gollnick H, Gielen S, Frank J, Beck S, Zrenner E. Phenotype in retinol deficiency due to a hereditary defect in retinol binding protein synthesis.  Invest Ophthalmol Vis Sci. 1999;  40(1) 3-11
    PubMedGoogle Scholar
  • 76 Quadro L, Hamberger L, Gottesman M E, Wang F, Colantuoni V, Blaner W S, Mendelsohn C L. Pathways of vitamin A delivery to the embryo: insights from a new tunable model of embryonic vitamin A deficiency.  Endocrinology. 2005;  146(10) 4479-4490
    CrossrefPubMedGoogle Scholar
  • 77 Wojnar P, Lechner M, Merschak P, Redl B. Molecular cloning of a novel lipocalin-1 interacting human cell membrane receptor using phage display.  J Biol Chem. 2001;  276(23) 20 206-20 212
    PubMedGoogle Scholar
  • 78 Wojnar P, Lechner M, Redl B. Antisense down-regulation of lipocalin-interacting membrane receptor expression inhibits cellular internalization of lipocalin-1 in human NT2 cells.  J Biol Chem. 2003;  278(18) 16 209-16 215
    PubMedGoogle Scholar
  • 79 Redl B, Holzfeind P, Lottspeich F. cDNA cloning and sequencing reveals human tear prealbumin to be a member of the lipophilic-ligand carrier protein superfamily.  J Biol Chem. 1992;  267(28) 20 282-20 287
    PubMedGoogle Scholar
  • 80 Glasgow B J, Abduragimov A R, Farahbakhsh Z T, Faull K F, Hubbell W L. Tear lipocalins bind a broad array of lipid ligands.  Curr Eye Res. 1995;  14(5) 363-372
    PubMedGoogle Scholar
  • 81 Briand L, Eloit C, Nespoulous C, Bezirard V, Huet J C, Henry C, Blon F, Trotier D, Pernollet J C. Evidence of an odorant-binding protein in the human olfactory mucus: location, structural characterization, and odorant-binding properties.  Biochemistry. 2002;  41(23) 7241-7252
    CrossrefPubMedGoogle Scholar
  • 82 Gasymov O K, Abduragimov A R, Gasimov E O, Yusifov T N, Dooley A N, Glasgow B J. Tear lipocalin: potential for selective delivery of rifampin.  Biochim Biophys Acta. 2004;  1688(2) 102-111
    PubMedGoogle Scholar
  • 83 Fluckinger M, Haas H, Merschak P, Glasgow B J, Redl B. Human tear lipocalin exhibits antimicrobial activity by scavenging microbial siderophores.  Antimicrob Agents Chemother. 2004;  48(9) 3367-3372
    CrossrefPubMedGoogle Scholar
  • 84 Holzfeind P, Redl B. Structural organization of the gene encoding the human lipocalin tear prealbumin and synthesis of the recombinant protein in Escherichia coli.  Gene. 1994;  139(2) 177-183
    CrossrefPubMedGoogle Scholar
  • 85 Lechner M, Wojnar P, Redl B. Human tear lipocalin acts as an oxidative-stress-induced scavenger of potentially harmful lipid peroxidation products in a cell culture system.  Biochem J. 2001;  356 (Pt 1) 129-135
    CrossrefPubMedGoogle Scholar
  • 86 Akerstrom B, Flower D R, Salier J P. Lipocalins: unity in diversity.  Biochim Biophys Acta. 2000;  1482(1 - 2) 1-8
    PubMedGoogle Scholar
  • 87 Goetz D H, Holmes M A, Borregaard N, Bluhm M E, Raymond K N, Strong R K. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition.  Mol Cell. 2000;  10(5) 1033-1043
    PubMedGoogle Scholar
  • 88 Loomis L D, Raymond K N. Solution equilibria of enterobactin and metal-enterobactin complexes.  Inorg Chem. 1991;  30 906-911
    CrossrefPubMedGoogle Scholar
  • 89 Yang J, Goetz D, Li J Y, Wang W, Mori K, Setlik D, Du T, Erdjument-Bromage H, Tempst P, Strong R, Barasch J. An iron delivery pathway mediated by a lipocalin.  Mol Cell. 2002;  10(5) 1045-1056
    CrossrefPubMedGoogle Scholar
  • 90 Collins J F, Franck C A, Kowdley K V, Ghishan F K. Identification of differentially expressed genes in response to dietary iron deprivation in rat duodenum.  Am J Physiol Gastrointest Liver Physiol. 2005;  288(5) 964-971
    CrossrefPubMedGoogle Scholar
  • 91 Kushner P J, Hort E, Shine J, Baxter J D, Greene G L. Construction of cell lines that express high levels of the human estrogen receptor and are killed by estrogens.  Mol Endocrinol. 1990;  4(10) 1465-1473
    PubMedGoogle Scholar
  • 92 Watson C S, Pappas T C, Gametchu B. The other estrogen receptor in the plasma membrane: implications for the actions of environmental estrogens.  Environ Health Perspect. 1995;  103 (Suppl 7) 41-50
    PubMedGoogle Scholar

J. B. C. Findlay

Department of Biochemistry and Microbiology

University of Leeds · Mount Preston Road · LS2 9JT Leeds · United Kingdom

Fax: +44 (113) 343-3167

Email: j.b.c.findlay@leeds.ac.uk