Abstract
Studies on the mode of action of steroid hormones have had a pioneering role in the elucidation of eukaryotic gene regulation. Several principles, established by molecular endocrinologists, have proven to be of general validity, and have advanced our perception of transcriptional control. Two aspects have received major attention: (1) The identification of DNA sequence elements which confer hormonal inducibility to adjacent promoters. These hormone response elements (HRE) have been defined as specific binding sites for receptor molecules (Beato 1989). (2) The structure of the steroid receptor molecules has been elucidated in molecular detail (Evans 1988; Green and Chambon 1988). Gene cloning and transfer experiments have given us a precise picture of the domain structure of these molecules and of their interactions with hormone response elements. The concentration on these molecular aspects has increased the resolution of our understanding, but leaves a broad field of the dynamics and physiology of hormone action to be uncovered. This chapter will focus on the fate of the glucocorticoid receptor upon hormonal activation, and the regulation of receptor concentration and receptor phosphorylation will be described.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Ball, R., Friis, R., Schönenberger, C.A. and Groner, B. (1988) Prolactin regulation of ß-casein gene expression and of a 120 kDa protein in a cloned mouse mammary epithelial cell line. EM BO J. 7: 2089–2095
Beato, M. (1989) Gene regulation by steroid hormones. Cell 56: 335–344
Danielson, K.G., Oborn, C.J., Durban, E.M., Butel, J.S. and Medina, D. (1984) Epithelial mouse mammary cell line exhibiting normal morphogenesis in vivo and functional differentiation in vitro. Proc. Natl. Acad. Sci. USA 81: 3756–3760
Danielson, M., Northrop, J.P. and Ringold, G.M. (1986) The mouse glucocorticoid receptor: mapping of functional domains by cloning, sequencing and expression of wild type and mutant receptor proteins. EMBO J. 5: 2513–2522
Dong, Y., Poellinger, L., Gustafsson, J.A. and Okret, S. (1988) Regulation of glucocorticoid receptor expression: evidence for transcriptional and posttranscriptional mechanisms. Mol. Endocrinol. 2: 1256–1264
Doppler, W., Groner, B. and Ball, R. (1989) Prolactin and glucocorticoid hormones synergistically induce expression of transfected rat ß-casein gene promoter constructs in a mammary epithelial cell line. Proc. Natl. Acad. Sci. USA 86: 104–108
Evans, R.M. (1988) The steroid and thyroid hormone receptor superfamily. Science 240: 889–895
Green, S. and Chambon, P. (1988) Nuclear receptors enhance our understanding of transcriptional regulation. Trends Genet. 4: 309–314
Groner, B., Hynes, N.E., Rahmsdorf, U. and Ponta, H. (1983) Transcription initiation of transfected mouse mammary tumor virus LTR DNA is regulated by glucocorticoid hormones. Nucl. Acids Res. 11: 4713–4725
Höck, W., Rusconi, S. and Groner, B. (1989a) Downregulation and phosphorylation of glucocorticoid receptors in vivo: investigations with a monospecific antiserum against a bacterially expressed receptor fragment. Biol. Chem. 264:No 24
Höck, W., Pfahl, M., Jaggi, R. and Groner, B. (1989b) Ligand induced downregulation of glucocorticoid receptors is enhanced by the expression of oncogenes. In: Lippman, M. and Dickson, R. (eds) Growth regulation of cancer. II. Liss, New York
Hollenberg, S.M. and Evans, R.M. (1988) Multiple and cooperative trans-activation domains of the human glucocorticoid receptor. Cell 55: 899–906
Hollenberg, S.M., Giguére, V., Segui, P. and Evans, R.M. (1987) Co-localisation of DNA binding and transcriptional activation functions in the human glucocorticoid receptor. Cell 49: 39–46
Housley, P.R. and Pratt, W.B. (1983) Direct demonstration of glucocorticoid receptor phosphorylation by intact L-cells. J. Biol. Chem. 258: 4630–4635
Jaggi, R., Salmons, B., Müllener, D. and Groner, B. (1986) The v-mos and H-ras oncogene expression represses glucocorticoid hormone dependent transcription from the mouse mammary tumor virus LTR. EMBO J. 5: 2609–2616
Jaggi, R., Salmons, B., Müllener, D. and Groner, B. (1986) The v-mos and H-ras oncogene expression represses glucocorticoid hormone dependent transcription from the mouse mammary tumor virus LTR. EMBO J. 5: 2609–2616
Kalinyak, J.E., Dorin, R.I., Hoffman, A.R. and Perlman, A.J. (1987) Tissue specific regulation of glucocorticoid receptor mRNA by dexamethasone. J. Biol. Chem. 262: 10441–10444
Lee, E.Y., Lee, H.P., Kaetzel, C.S., Parry, G. and Bissell, M.J. (1985) Interaction of mouse mammary epithelial cells with collagen substrata: regulation of casein gene expression and secretion. Proc. Natl. Acad. Sci. USA 82: 1419–1432
McIntyre, W.R. and Samuels, H.H. (1985) Triamcinolone acetonide regulates glucocorticoid receptor levels by decreasing the half-life of the activated nuclear receptor form. J. Biol. Chem. 260: 418–427
Okret, S., Poellinger, L., Dong, Y. and Gustafsson, J.A. (1986) Downregulation of glucocorticoid receptor mRNA by glucocorticoid hormones and recognition by the receptor of a specific binding sequence within a receptor cDNA clone. Proc. Natl. Acad. Sci. USA 83: 5899–5903
Pfahl, M., Sandros, T. and Bourgeois, S. (1978) Interaction of glucocorticoid receptors from lymphoid cell lines with their nuclear acceptor sites. Mol. Cell. Endocrinol. 10: 175–191
Rosewicz, S., McDonald, A.R., Maddux, B.A., Goldfine, I.D., Miesfeld, R.L. and Logsdon, C.D. (1988) Mechanism of glucocorticoid receptor downregulation by glucocorticoids. J. Biol. Chem. 263: 2581–2584
Topper, Y. and Freeman, C.S. (1980) Multiple hormone interactions in the developmental biology of the mammary gland. Physiol. Rev. 60: 1049–1106
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1989 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Groner, B., Höck, W., Doppler, W., Ball, R. (1989). Modulation of Glucocorticoid Hormone Action by Oncogenes and Peptide Hormones. In: Gehring, U., Helmreich, E.J.M., Schultz, G. (eds) Molecular Mechanisms of Hormone Action. 40. Colloquium der Gesellschaft für Biologische Chemie 6.– 8. April 1989 in Mosbach/Baden, vol 40. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-75022-9_7
Download citation
DOI: https://doi.org/10.1007/978-3-642-75022-9_7
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-75024-3
Online ISBN: 978-3-642-75022-9
eBook Packages: Springer Book Archive