Skip to main content
SpringerLink
Log in

Steroid Receptors

  • Chapter
Transgenic Models in Pharmacology

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 159))

  • 126 Accesses

Abstract

Steroids are lipophilic hormones and regulate multiple functions in development, physiology, and reproduction by binding to their cognate receptors. Steroid receptors are intracellular proteins that transduce biological signals into direct transcriptional responses. Because of both the lipophilic nature of the steroid signal and the immediacy of the signal transmission, steroid receptors make ideal drug targets. Sex steroid receptors (estrogen receptor, progesterone receptor, androgen receptor) have shown to be dispensable for mammalian development and survival. The fact that estrogen, progesterone, and androgen receptor knockout mice survive until adulthood has made these mouse models versatile tools for pharmacological studies in vivo. Corticosteroid receptors (glucocorticoid and mineralocorticoid receptor) have been shown to be essential for survival by early lethality of the respective knockout mouse models. Conditional gene targeting strategies for generating, restricting, and refining mutations in mice facilitate analysis of glucocorticoid and mineralocorticoid receptor functions in later development and adult physiology. For instance, allelic series of glucocorticoid receptor mutants with a wide range of cell-specific and function-selective defects allow dissecting glucocorticoid receptor functions in mice. For steroid pharmacology, these mouse models provide an unprecedented resource to understand drug action and drug target functions in vivo.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Balsalobre, A., Brown, S. A., Marcacci, L., Tronche, F., Kellendonk, C., Reichardt, H. M., Schutz, G., and Schibler, U. (2000) Resetting of circadian time in peripheral tissues by glucocorticoid signaling. Science 289, 2344–7

    Article  PubMed  CAS  Google Scholar 

  • Barden, N. (1994) Corticosteroid receptor modulation in transgenic mice. Ann N YAcad Sci 746, 89–98; discussion 98-100, 131-3

    Article  CAS  Google Scholar 

  • Barden, N. (1996) Modulation of glucocorticoid receptor gene expression by antidepressant drugs. Pharmacopsychiatry 29, 12–22

    Article  PubMed  CAS  Google Scholar 

  • Barden, N. (1999) Regulation of corticosteroid receptor gene expression in depression and antidepressant action. J Psychiatry Neurosci 24, 25–39

    PubMed  CAS  Google Scholar 

  • Barden, N., Stec, I. S., Montkowski, A., Holsboer, F., and Reul, J. M. (1997) Endocrine profile and neuroendocrine challenge tests in transgenic mice expressing antisense RNA against the glucocorticoid receptor. Neuroendocrinology 66, 212–20

    Article  PubMed  CAS  Google Scholar 

  • Bauer, A., Tronche, F., Wessely, O., Kellendonk, C., Reichardt, H. M., Steinlein, P., Schutz, G., and Beug, H. (1999) The glucocorticoid receptor is required for stress erythropoiesis. Genes Dev 13, 2996–3002

    Article  PubMed  CAS  Google Scholar 

  • Beato, M., Herrlich, P., and Schutz, G. (1995) Steroid hormone receptors: many actors in search of a plot. Cell 83, 851–7

    Article  PubMed  CAS  Google Scholar 

  • Beggah, A. T., Escoubet, B., Puttini, S., Cailmail, S., Delage, V., Ouvrard-Pascaud, A., Bocchi, B., Peuchmaur, M., Delcayre, C., Farman, N., and Jaisser, F. (2002) Reversible cardiac fibrosis and heart failure induced by conditional expression of an antisense mRNA of the mineralocorticoid receptor in cardiomyocytes. Proc Natl Acad Sci USA 7, 7

    Google Scholar 

  • Berger, S., Bleich, M., Schmid, W., Cole, T. J., Peters, J., Watanabe, H., Kriz, W., Warth, R., Greger, R., and Schutz, G. (1998) Mineralocorticoid receptor knockout mice: pathophysiology of Na+ metabolism. Proc Natl Acad Sci USA 95, 9424–9

    Article  PubMed  CAS  Google Scholar 

  • Berger, S., Cole, T. J., Schmid, W., and Schutz, G. (1996) Analysis of glucocorticoid and mineralocorticoid signalling by gene targeting. Endocr Res 22, 641–52

    PubMed  CAS  Google Scholar 

  • Bingham, P. M., Scott, M. O., Wang, S., McPhaul, M. J., Wilson, E. M., Garbern, J. Y., Merry, D. E., and Fischbeck, K. H. (1995) Stability of an expanded trinucleotide repeat in the androgen receptor gene in transgenic mice. Nat Genet 9, 191–6

    Article  PubMed  CAS  Google Scholar 

  • Bledsoe, R. K., Montana, V. G., Stanley, T. B., Delves, C. J., Apolito, C. J., McKee, D. D., Consler, T. G., Parks, D. J., Stewart, E. L., Willson, T. M., Lambert, M. H., Moore, J. T., Pearce, K. H., and Xu, H. E. (2002) Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell 110, 93–105

    Article  PubMed  CAS  Google Scholar 

  • Bleich, M., Warth, R., Schmidt-Hieber, M., Schulz-Baldes, A., Hasselblatt, P., Fisch, D., Berger, S., Kunzelmann, K., Kriz, W., Schutz, G., and Greger, R. (1999) Rescue of the mineralocorticoid receptor knock-out mouse. Pflugers Arch 438, 245–54. ny.com/ link/service/journals/00424/bibs/438n3p245.html

    Article  PubMed  CAS  Google Scholar 

  • Bocchinfuso, W P., Lindzey, J. K., Hewitt, S. C., Clark, J. A., Myers, P. H., Cooper, R., and Korach, K. S. (2000) Induction of mammary gland development in estrogen receptoralpha knockout mice. Endocrinology 141, 2982–94

    Article  PubMed  CAS  Google Scholar 

  • Bredenberg, J., and Nilsson, L. (2002) Conformational states of the glucocorticoid receptor DNA-binding domain from molecular dynamics simulations. Proteins 49, 24–36

    Article  PubMed  CAS  Google Scholar 

  • Brisken, C., Heineman, A., Chavarria, T., Elenbaas, B., Tan, J., Dey, S. K., McMahon, J. A., McMahon, A. P., and Weinberg, R. A. (2000) Essential function of Wnt-4 in mammary gland development downstream of progesterone signaling. Genes Dev 14, 650–4

    PubMed  CAS  Google Scholar 

  • Brouchet, L., Krust, A., Dupont, S., Chambon, P., Bayard, F., and Arnal, J. F. (2001) Estradiol accelerates reendothelialization in mouse carotid artery through estrogen receptor-alpha but not estrogen receptor-beta. Circulation 103, 423–8

    Article  PubMed  CAS  Google Scholar 

  • Brzozowski, A. M., Pike, A. C., Dauter, Z., Hubbard, R. E., Bonn, T., Engstrom, O., Ohman, L., Greene, G. L., Gustafsson, J. A., and Carlquist, M. (1997) Molecular basis of agonism and antagonism in the oestrogen receptor. Nature 389, 753–8

    Article  PubMed  CAS  Google Scholar 

  • Chatterjee, B., Song, C. S., Jung, M. H., Chen, S., Walter, C. A., Herbert, D. C., Weaker, F. J., Mancini, M. A., and Roy, A. K. (1996) Targeted overexpression of androgen receptor with a liver-specific promoter in transgenic mice. Proc Natl Acad Sci USA 93, 728–33

    Article  PubMed  CAS  Google Scholar 

  • Chow, J. C., Ling, P. R., Qu, Z., Laviola, L., Ciccarone, A., Bistrian, B. R., and Smith, R. J. (1996) Growth hormone stimulates tyrosine phosphorylation of JAK2 and STAT5, but not insulin receptor substrate-1 or SHC proteins in liver and skeletal muscle of normal rats in vivo. Endocrinology 137, 2880–6

    Article  PubMed  CAS  Google Scholar 

  • Ciana, P., Di Luccio, G., Belcredito, S., Pollio, G., Vegeto, E., Tatangelo, L., Tiveron, C., and Maggi, A. (2001) Engineering of a mouse for the in vivo profiling of estrogen receptor activity. Mol Endocrinol 15, 1104–13

    Article  PubMed  CAS  Google Scholar 

  • Ciana, P., Raviscioni, M., Mussi, P., Vegeto, E., Que, I., Parker, M. G., Lowik, C., and Maggi, A. (2002) In vivo imaging of transcriptionally active estrogen receptors. Nat Med 16, 16

    Google Scholar 

  • Cole, T. J., Blendy, J. A., Monaghan, A. P., Krieglstein, K., Schmid, W., Aguzzi, A., Fantuzzi, G., Hummler, E., Unsicker, K., and Schutz, G. (1995) Targeted disruption of the glucocorticoid receptor gene blocks adrenergic chromaffin cell development and severely retards lung maturation. Genes Dev 9, 1608–21

    Article  PubMed  CAS  Google Scholar 

  • Conneely, O. M., and Jericevic, B. M. (2002) Progesterone regulation of reproductive function through functionally distinct progesterone receptor isoforms. Rev Endocr Metab Disord 3, 201–9

    Article  PubMed  CAS  Google Scholar 

  • Conneely, O. M., Mulac-Jericevic, B., DeMayo, R, Lydon, J. P., and O’Malley, B. W. (2002) Reproductive functions of progesterone receptors. Recent Prog Horm Res 57, 339–55

    Article  PubMed  CAS  Google Scholar 

  • Conneely, O. M., Mulac-Jericevic, B., Lydon, J. P., and De Mayo, F. J. (2001) Reproductive functions of the progesterone receptor isoforms: lessons from knock-out mice. Mol Cell Endocrinol 179, 97–103

    Article  PubMed  CAS  Google Scholar 

  • Couse, J. F., Bunch, D. O., Lindzey, J., Schomberg, D. W., and Korach, K. S. (1999) Prevention of the polycystic ovarian phenotype and characterization of ovulatory capacity in the estrogen receptor-alpha knockout mouse. Endocrinology 140, 5855–65

    Article  PubMed  CAS  Google Scholar 

  • Couse, J. F., Hewitt, S. C., Bunch, D. O., Sar, M., Walker, V. R., Davis, B. J., and Korach, K. S. (1999) Postnatal sex reversal of the ovaries in mice lacking estrogen receptors alpha and beta. Science 286, 2328–31

    Article  PubMed  CAS  Google Scholar 

  • Couse, J. F., and Korach, K. S. (1999) Estrogen receptor null mice: what have we learned and where will they lead us? Endocr Rev 20, 358–417

    Article  PubMed  CAS  Google Scholar 

  • Curtis, S. W., Washburn, T., Sewall, C., DiAugustine, R., Lindzey, J., Couse, J. F., and Korach, K. S. (1996) Physiological coupling of growth factor and steroid receptor signaling pathways: estrogen receptor knockout mice lack estrogen-like response to epidermal growth factor. Proc Natl Acad Sci USA 93, 12626–30

    Article  PubMed  CAS  Google Scholar 

  • Darblade, B., Pendaries, C., Krust, A., Dupont, S., Fouque, M. J., Rami, J., Chambon, P., Bayard, F., and Arnal, J. F. (2002) Estradiol alters nitric oxide production in the mouse aorta through the alpha-, but not beta-, estrogen receptor. Circ Res 90, 413–9

    Article  PubMed  CAS  Google Scholar 

  • Dick, G. M., Rossow, C. F., Smirnov, S., Horowitz, B., and Sanders, K. M. (2001) Tamoxifen activates smooth muscle BK channels through the regulatory beta 1 subunit. J Biol Chem 276, 34594–9

    Article  PubMed  CAS  Google Scholar 

  • Drouin, J., Sun, Y. L., Chamberland, M., Gauthier, Y., De Lean, A., Nemer, M., and Schmidt, T. J. (1993) Novel glucocorticoid receptor complex with DNA element of the hormone-repressed POMC gene. Embo J 12, 145–56

    PubMed  CAS  Google Scholar 

  • Dupont, S., Krust, A., Gansmuller, A., Dierich, A., Chambon, P., and Mark, M. (2000) Effect of single and compound knockouts of estrogen receptors alpha (ERalpha) and beta (ERbeta) on mouse reproductive phenotypes. Development 127, 4277–91

    PubMed  CAS  Google Scholar 

  • Freedman, L. P., Luisi, B. F., Korszun, Z. R., Basavappa, R., Sigler, P. B., and Yamamoto, K. R. (1988) The function and structure of the metal coordination sites within the glucocorticoid receptor DNA binding domain. Nature 334, 543–6

    Article  PubMed  CAS  Google Scholar 

  • Funder, J. W., Pearce, P. T., Smith, R., and Smith, A. I. (1988) Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated. Science 242, 583–5

    Article  PubMed  CAS  Google Scholar 

  • Geller, D. S., Farhi, A., Pinkerton, N., Fradley, M., Moritz, M., Spitzer, A., Meinke, G., Tsai, F. T., Sigler, P. B., and Lifton, R. P. (2000) Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science 289, 119–23

    Article  PubMed  CAS  Google Scholar 

  • Gu, H., Marth, J. D., Orban, P. C., Mossmann, H., and Rajewsky, K. (1994) Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting. Science 265, 103–6

    Article  PubMed  CAS  Google Scholar 

  • Harvey, B. J., Doolan, C. M., Condliffe, S. B., Renard, C., Alzamora, R., and Urbach, V. (2002) Non-genomic convergent and divergent signalling of rapid responses to aldosterone and estradiol in mammalian colon. Steroids 67, 483–91

    Article  PubMed  CAS  Google Scholar 

  • Hinz, B., and Hirschelmann, R. (2000) Rapid non-genomic feedback effects of glucocorticoids on CRF-induced ACTH secretion in rats. Pharm Res 17, 1273–7

    Article  PubMed  CAS  Google Scholar 

  • Hubert, C., Gasc, J. M., Berger, S., Schutz, G., and Corvol, P. (1999) Effects of mineralocorticoid receptor gene disruption on the components of the renin-angiotensin system in 8-day-old mice. Mol Endocrinol 13, 297–306

    Article  PubMed  CAS  Google Scholar 

  • Iafrati, M. D., Karas, R. H., Aronovitz, M., Kim, S., Sullivan, T. R., Jr., Lubahn, D. B., O’Donnell, T. R, Jr., Korach, K. S., and Mendelsohn, M. E. (1997) Estrogen inhibits the vascular injury response in estrogen receptor alpha-deficient mice. Nat Med 3, 545–8

    Article  PubMed  CAS  Google Scholar 

  • Jacq, X., Brou, C., Lutz, Y., Davidson, I., Chambon, P., and Tora, L. (1994) Human TAFII30 is present in a distinct TFIID complex and is required for transcriptional activation by the estrogen receptor. Cell 79, 107–17

    Article  PubMed  CAS  Google Scholar 

  • Jaisser, F. (2000) Inducible gene expression and gene modification in transgenic mice. J Am Soc Nephrol 11 Suppl 16, S95–S100

    PubMed  CAS  Google Scholar 

  • Jakacka, M., Ito, M., Martinson, F., Ishikawa, T., Lee, E. J., and Jameson, J. L. (2002) An estrogen receptor (ER)alpha deoxyribonucleic acid-binding domain knock-in mutation provides evidence for nonclassical ER pathway signaling in vivo. Mol Endocrinol 16, 2188–201

    Article  PubMed  CAS  Google Scholar 

  • Jakacka, M., Ito, M., Weiss, J., Chien, P. Y., Gehm, B. D., and Jameson, J. L. (2001) Estrogen receptor binding to DNA is not required for its activity through the nonclassical AP1 pathway. J Biol Chem 276, 13615–21

    PubMed  CAS  Google Scholar 

  • Kato, S., Endoh, H., Masuhiro, Y., Kitamoto, T., Uchiyama, S., Sasaki, H., Masushige, S., Gotoh, Y., Nishida, E., Kawashima, H., and et al. (1995) Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science 270, 1491–4

    Article  PubMed  CAS  Google Scholar 

  • Kellendonk, C., Opherk, C., Anlag, K., Schutz, G., and Tronche, F. (2000) Hepatocyte-specific expression of Cre recombinase. Genesis 26, 151–3

    Article  PubMed  CAS  Google Scholar 

  • Klotz, D. M., Hewitt, S. C., Ciana, P., Raviscioni, M., Lindzey, J. K., Foley, J., Maggi, A., DiAugustine, R. P., and Korach, K. S. (2002) Requirement of estrogen receptor-alpha in IGF-1-induced uterine responses and in vivo evidence for IGF-1/estrogen receptor cross-talk. J Biol Chem 277, 8531–7

    Article  PubMed  CAS  Google Scholar 

  • Korach, K. S. (2000) Estrogen receptor knock-out mice: molecular and endocrine phenotypes. J Soc Gynecol Investig 7, S16–7

    Article  PubMed  CAS  Google Scholar 

  • Korach, K. S., Couse, J. F., Curtis, S. W., Washburn, T. F., Lindzey, J., Kimbro, K. S., Eddy, E. M., Migliaccio, S., Snedeker, S. M., Lubahn, D. B., Schomberg, D. W., and Smith, E. P. (1996) Estrogen receptor gene disruption: molecular characterization and experimental and clinical phenotypes. Recent Prog Horm Res 51, 159–86

    PubMed  CAS  Google Scholar 

  • Kos, M., Denger, S., Reid, G., and Gannon, F. (2002a) Upstream open reading frames regulate the translation of the multiple mRNA variants of the estrogen receptor alpha. J Biol Chem 277, 37131–8

    Article  PubMed  CAS  Google Scholar 

  • Kos, M., Denger, S., Reid, G., Korach, K. S., and Gannon, F. (2002b) Down but not out? A novel protein isoform of the estrogen receptor alpha is expressed in the estrogen receptor alpha knockout mouse. J Mol Endocrinol 29, 281–6

    Article  PubMed  CAS  Google Scholar 

  • Krege, J. H., Hodgin, J. B., Couse, J. F., Enmark, E., Warner, M., Mahler, J. F., Sar, M., Korach, K. S., Gustafsson, J. A., and Smithies, O. (1998) Generation and reproductive phenotypes of mice lacking estrogen receptor beta. Proc Natl Acad Sci USA 95, 15677–82

    Article  PubMed  CAS  Google Scholar 

  • Kuiper, G. G., Enmark, E., Pelto-Huikko, M., Nilsson, S., and Gustafsson, J. A. (1996) Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 93, 5925–30

    Article  PubMed  CAS  Google Scholar 

  • La Spada, A. R., Peterson, K. R., Meadows, S. A., McClain, M. E., Jeng, G., Chmelar, R. S., Haugen, H. A., Chen, K., Singer, M. J., Moore, D., Trask, B. J., Fischbeck, K. H., Clegg, C. H., and McKnight, G. S. (1998) Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability. Hum Mol Genet 7, 959–67

    Article  PubMed  CAS  Google Scholar 

  • Laudet, V., and Gronemeyer, H. (2001) The Nuclear Receptor FactsBook, 1st edition (November 2001) Edition: Academic Press)

    Google Scholar 

  • Lees, J. A., Fawell, S. E., and Parker, M. G. (1989) Identification of two transactivation domains in the mouse oestrogen receptor. Nucleic Acids Res 17, 5477–88

    Article  PubMed  CAS  Google Scholar 

  • Lubahn, D. B., Moyer, J. S., Golding, T. S., Couse, J. F., Korach, K. S., and Smithies, O. (1993) Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc Natl Acad Sci USA 90, 11162–6

    Article  PubMed  CAS  Google Scholar 

  • Luisi, B. F., Xu, W. X., Otwinowski, Z., Freedman, L. P., Yamamoto, K. R., and Sigler, P. B. (1991) Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA. Nature 352, 497–505

    Article  PubMed  CAS  Google Scholar 

  • Marchetti, B., Morale, M. C., Testa, N., Tirolo, C., Caniglia, S., Amor, S., Dijkstra, C. D., and Barden, N. (2001) Stress, the immune system and vulnerability to degenerative disorders of the central nervous system in transgenic mice expressing glucocorticoid receptor antisense RNA. Brain Res Brain Res Rev 37, 259–72

    Article  PubMed  CAS  Google Scholar 

  • Marchetti, B., Peiffer, A., Morale, M. C., Batticane, N., Gallo, F., and Barden, N. (1994) Transgenic animals with impaired type II glucocorticoid receptor gene expression. A model to study aging of the neuroendocrine-immune system. Ann N Y Acad Sci 719, 308–27

    Article  PubMed  CAS  Google Scholar 

  • Matias, P. M., Carrondo, M. A., Coelho, R., Thomaz, M., Zhao, X. Y., Wegg, A., Crusius, K., Egner, U., and Donner, P. (2002) Structural basis for the glucocorticoid response in a mutant human androgen receptor (AR(ccr)) derived from an androgen-independent prostate cancer. J Med Chem 45, 1439–46

    Article  PubMed  CAS  Google Scholar 

  • Metcalf, D., Greenhalgh, C. J., Viney, E., Willson, T. A., Starr, R., Nicola, N. A., Hilton, D. J., and Alexander, W. S. (2000) Gigantism in mice lacking suppressor of cytokine siγnallinγ-2. Nature 405, 1069–73

    Article  PubMed  CAS  Google Scholar 

  • Metzger, D., Ali, S., Bornert, J. M., and Chambon, P. (1995) Characterization of the amino-terminal transcriptional activation function of the human estrogen receptor in animal and yeast cells. J Biol Chem 270, 9535–42

    Article  PubMed  CAS  Google Scholar 

  • Mulac-Jericevic, B., Mullinax, R. A., DeMayo, R J., Lydon, J. P., and Conneely, O. M. (2000) Subgroup of reproductive functions of progesterone mediated by progesterone receptor-B isoform. Science 289, 1751–4

    Article  PubMed  CAS  Google Scholar 

  • Nagel, S. C., Hagelbarger, J. L., and McDonnell, D. P. (2001) Development of an ER action indicator mouse for the study of estrogens, selective ER modulators (SERMs), and Xenobiotics. Endocrinology 142, 4721–8

    Article  PubMed  CAS  Google Scholar 

  • Paech, K., Webb, P., Kuiper, G. G., Nilsson, S., Gustafsson, J., Kushner, P. J., and Scanlan, T. S. (1997) Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites. Science 277, 1508–10

    Article  PubMed  CAS  Google Scholar 

  • Parker, M. G. (1998) Transcriptional activation by oestrogen receptors. Biochem Soc Symp 63, 45–50

    PubMed  CAS  Google Scholar 

  • Pearce, P. T., and Funder, J. W. (1988) Steroid binding to cardiac type I receptors: in vivo studies. J Hypertens Suppl 6, S131–3

    PubMed  CAS  Google Scholar 

  • Pendaries, C., Darblade, B., Rochaix, P., Krust, A., Chambon, P., Korach, K. S., Bayard, F., and Arnal, J. F. (2002) The AF-1 activation-function of ERalpha may be dispensable to mediate the effect of estradiol on endothelial NO production in mice. Proc Natl Acad Sci USA 99, 2205–10

    Article  PubMed  CAS  Google Scholar 

  • Rae, M. T., Menzies, G. S., McNeilly, A. S., Woad, K., Webb, R., and Bramley, T. A. (1998) Specific non-genomic, membrane-localized binding sites for progesterone in the bovine corpus luteum. Biol Reprod 58, 1394–406

    Article  PubMed  CAS  Google Scholar 

  • Reichardt, H. M., Kaestner, K. H., Tuckermann, J., Kretz, O., Wessely, O., Bock, R., Gass, P., Schmid, W., Herrlich, P., Angel, P., and Schutz, G. (1998) DNA binding of the glucocorticoid receptor is not essential for survival. Cell 93, 531–41

    Article  PubMed  CAS  Google Scholar 

  • Reichardt, H. M., Kellendonk, C., Tronche, F., and Schutz, G. (1999) The Cre/loxP system-a versatile tool to study glucocorticoid signalling in mice. Biochem Soc Trans 27, 78–83

    PubMed  CAS  Google Scholar 

  • Reichardt, H. M., Tuckermann, J. P., Gottlicher, M., Vujic, M., Weih, F., Angel, P., Herrlich, P., and Schutz, G. (2001) Repression of inflammatory responses in the absence of DNA binding by the glucocorticoid receptor. Embo J 20, 7168–73

    Article  PubMed  CAS  Google Scholar 

  • Reichardt, H. M., Umland, T., Bauer, A., Kretz, O., and Schutz, G. (2000) Mice with an increased glucocorticoid receptor gene dosage show enhanced resistance to stress and endotoxic shock. Mol Cell Biol 20, 9009–17

    Article  PubMed  CAS  Google Scholar 

  • Robin-Jagerschmidt, C., Wurtz, J. M., Guillot, B., Gofflo, D., Benhamou, B., Vergezac, A., Ossart, C., Moras, D., and Philibert, D. (2000) Residues in the ligand binding domain that confer progestin or glucocorticoid specificity and modulate the receptor transactivation capacity. Mol Endocrinol 14, 1028–37

    Article  PubMed  CAS  Google Scholar 

  • Robinson, G. W., Hennighausen, L., and Johnson, P. F. (2000) Side-branching in the mammary gland: the progesterone-Wnt connection. Genes Dev 14, 889–94

    PubMed  CAS  Google Scholar 

  • Sato, T., Kawano, H., and Kato, S. (2002) Study of androgen action in bone by analysis of androgen-receptor deficient mice. J Bone Miner Metab 20, 326–30

    Article  PubMed  Google Scholar 

  • Sato, T., Matsumoto, T., Yamada, T., Watanabe, T., Kawano, H., and Kato, S. (2003) Late onset of obesity in male androgen receptor-deficient (AR KO) mice. Biochem Biophys Res Commun 300, 167–71

    Article  PubMed  CAS  Google Scholar 

  • Shang, Y., and Brown, M. (2002) Molecular determinants for the tissue specificity of SERMs. Science 295, 2465–8

    Article  PubMed  CAS  Google Scholar 

  • Shang, Y., Hu, X., DiRenzo, J., Lazar, M. A., and Brown, M. (2000) Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription. Cell 103, 843–52

    Article  PubMed  CAS  Google Scholar 

  • Shiau, A. K., Barstad, D., Radek, J. T., Meyers, M. J., Nettles, K. W., Katzenellenbogen, B. S., Katzenellenbogen, J. A., Agard, D. A., and Greene, G. L. (2002) Structural characterization of a subtype-selective ligand reveals a novel mode of estrogen receptor antagonism. Nat Struct Biol 9, 359–64

    PubMed  CAS  Google Scholar 

  • Shyamala, G., Yang, X., Cardiff, R. D., and Dale, E. (2000) Impact of progesterone receptor on cell-fate decisions during mammary gland development. Proc Natl Acad Sci USA 97, 3044–9

    Article  PubMed  CAS  Google Scholar 

  • Shyamala, G., Yang, X., Silberstein, G., Barcellos-Hoff, M. H., and Dale, E. (1998) Transgenic mice carrying an imbalance in the native ratio of A to B forms of progesterone receptor exhibit developmental abnormalities in mammary glands. Proc Natl Acad Sci USA 95, 696–701

    Article  PubMed  CAS  Google Scholar 

  • Sillaber, I., Rammes, G., Zimmermann, S., Mahal, B., Zieglgansberger, W., Wurst, W., Holsboer, F., and Spanagel, R. (2002) Enhanced and delayed stress-induced alcohol drinking in mice lacking functional CRH1 receptors. Science 296, 931–3

    Article  PubMed  CAS  Google Scholar 

  • Simoncini, T., Hafezi-Moghadam, A., Brazil, D. P., Ley, K., Chin, W. W., and Liao, J. K. (2000) Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature 407, 538–41

    Article  PubMed  CAS  Google Scholar 

  • Stec, I., Barden, N., Reul, J. M., and Holsboer, F. (1994) Dexamethasone nonsuppression in transgenic mice expressing antisense RNA to the glucocorticoid receptor. J Psychiatr Res 28, 1–5

    Article  PubMed  CAS  Google Scholar 

  • Stocklin, E., Wissler, M., Gouilleux, F., and Groner, B. (1996) Functional interactions between Stat5 and the glucocorticoid receptor. Nature 383, 726–8

    Article  PubMed  CAS  Google Scholar 

  • Tronche, F., Kellendonk, C., Kretz, O., Gass, P., Anlag, K., Orban, P. C., Bock, R., Klein, R., and Schutz, G. (1999) Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety. Nat Genet 23, 99–103. java/Propub/genetics/ ng0999_99.fulltextjava/Propub/genetics/ng0999_99.abstract

    Article  PubMed  CAS  Google Scholar 

  • Tronche, F., Kellendonk, C., Reichardt, H. M., and Schutz, G. (1998) Genetic dissection of glucocorticoid receptor function in mice. Curr Opin Genet Dev 8, 532–8

    Article  PubMed  CAS  Google Scholar 

  • Vidal, O., Lindberg, M. K., Hollberg, K., Baylink, D. J., Andersson, G., Lubahn, D. B., Mohan, S., Gustafsson, J. A., and Ohlsson, C. (2000) Estrogen receptor specificity in the regulation of skeletal growth and maturation in male mice. Proc Natl Acad Sci USA 97, 5474–9

    Article  PubMed  CAS  Google Scholar 

  • Wintermantel, T. M., Mayer, A. K., Schutz, G., and Greiner, E. F. (2002) Targeting mammary epithelial cells using a bacterial artificial chromosome. Genesis 33, 125–30

    Article  PubMed  CAS  Google Scholar 

  • Yeh, S., Tsai, M. Y., Xu, Q., Mu, X. M., Lardy, H., Huang, K. E., Lin, H., Yeh, S. D., Altuwaijri, S., Zhou, X., Xing, L., Boyce, B. F., Hung, M. C., Zhang, S., Gan, L., and Chang, C. (2002) Generation and characterization of androgen receptor knockout (ARKO) mice: an in vivo model for the study of androgen functions in selective tissues. Proc Natl Acad Sci USA 99, 13498–503

    Article  PubMed  CAS  Google Scholar 

  • Zhu, Y., Bian, Z., Lu, P., Karas, R. H., Bao, L., Cox, D., Hodgin, J., Shaul, P. W., Thoren, P., Smithies, O., Gustafsson, J. A., and Mendelsohn, M. E. (2002) Abnormal vascular function and hypertension in mice deficient in estrogen receptor beta. Science 295, 505–8

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Life Science Technology, Evotec OAI AG, Schnackenburgallee 114, 22525, Hamburg, Germany

    E. F. Greiner

  2. Division Molecular Biology of the Cell I, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    E. F. Greiner, T. Wintermantel & G. Schütz

Authors
  1. E. F. Greiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Wintermantel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Schütz
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Pharmakologisches Institut, Universität Heidelberg, Im Neuenheimer Feld 366, 69120, Heidelberg, Germany

    Stefan Offermanns

  2. Institut für Pharmakologie und Toxikologie der Universität, Versbacher Straße 9, 97078, Germany

    Lutz Hein

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Greiner, E.F., Wintermantel, T., Schütz, G. (2004). Steroid Receptors. In: Offermanns, S., Hein, L. (eds) Transgenic Models in Pharmacology. Handbook of Experimental Pharmacology, vol 159. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18934-0_19

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-18934-0_19

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62362-2

  • Online ISBN: 978-3-642-18934-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation