This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Forman, B. M. Articles by Samuels, H. H. Search for Related Content PubMed PubMed Citation Articles by Forman, B. M. Articles by Samuels, H. H.

c-erbA Protooncogenes Mediate Thyroid Hormone-Dependent and Independent Regulation of the Rat Growth Hormone and Prolactin Genes

The Division of Molecular Endocrinology, Department of Medicine, New York University Medical Center New York, New York 10016
The Department of Pharmacology, New York University Medical Center New York, New York 10016

Address requests for reprints to: Dr. Herbert H. Samuels, Division of Molecular Endocrinology, Department of Medicine, New York University Medical Center, 550 First Avenue, New York, New York 10016.

Abstract

Regulation of gene expression by the thyroid hormones is thought to be mediated by a nuclear-associated receptor found in a wide variety of cells and tissues. Cellular homologues of the avian erythroblastosis virus oncogene, v-erbA, encode proteins which bind thyroid hormone with similar affinities as thyroid hormone receptors. However, it has not been shown that any of the c-erbA proteins can function as receptor and modulate thyroid hormone responsive genes. In this study, using transient expression of chimeric reporter constructs, we document that the chick fibroblast c-erbA- and the human placental c-erbA-β modulate cis-acting regulatory sequences of two thyroid hormone responsive genes; rat GH and PRL. From these results we conclude: 1) in a receptor deficient cell line (235-1) both c-erbA subtypes act as hormone-dependent modulators of PRL gene expression and hence function as thyroid hormone receptors, 2) in two different receptor containing cell lines (GH₄C₁ and GH₁), both c-erbA proteins act in a hormone-independent fashion to regulate PRL and GH expression. This suggests that events other than ligand binding can result in formation of a c-erbA protein that modulates transcription of thyroid hormone responsive genes, 3) no qualitative functional differences were detected between - and β-c-erbA subtypes, and 4) depending on the cell-type, L-T₃ acts through its endogenous receptor to stimulate (GH₄C₁) or suppress (GH₁) expression of a chimeric PRL construct. In these cells, c-erbA expression results in the same positive or negative response as the endogenous receptor except that the response occurs in the absence of hormone. These results suggest that the endogenous receptor and the c-erbAs act by augmenting the effect of transcription factors which can positively or negatively control gene expression.

FOOTNOTES

This research was supported by NIH Research Grants DK-16636 (to H.H.S.) and DK-36615 (to F.S.) and an NIH Medical Scientist Training Grant (to B.M.F.).

Received for publication June 2, 1988. Accepted for publication June 25, 1988.

This article has been cited by other articles:

				S. Friedrichsen, S. Christ, H. Heuer, M. K. H. Schafer, A. F. Parlow, T. J. Visser, and K. Bauer Expression of Pituitary Hormones in the Pax8-/- Mouse Model of Congenital Hypothyroidism Endocrinology, March 1, 2004; 145(3): 1276 - 1283. [Abstract] [Full Text] [PDF]

				A. I. Castillo, R. Sanchez-Martinez, J. L. Moreno, O. A. Martinez-Iglesias, D. Palacios, and A. Aranda A Permissive Retinoid X Receptor/Thyroid Hormone Receptor Heterodimer Allows Stimulation of Prolactin Gene Transcription by Thyroid Hormone and 9-cis-Retinoic Acid Mol. Cell. Biol., January 15, 2004; 24(2): 502 - 513. [Abstract] [Full Text] [PDF]

				S. Danzi, K. Ojamaa, and I. Klein Triiodothyronine-mediated myosin heavy chain gene transcription in the heart Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H2255 - H2262. [Abstract] [Full Text] [PDF]

				R. Perez-Olle, C. L. Leung, and R. K. H. Liem Effects of Charcot-Marie-Tooth-linked mutations of the neurofilament light subunit on intermediate filament formation J. Cell Sci., March 14, 2003; 115(24): 4937 - 4946. [Abstract] [Full Text] [PDF]

				P. M. Yen Physiological and Molecular Basis of Thyroid Hormone Action Physiol Rev, July 1, 2001; 81(3): 1097 - 1142. [Abstract] [Full Text] [PDF]

				M. A. Mahajan and H. H. Samuels A New Family of Nuclear Receptor Coregulators That Integrate Nuclear Receptor Signaling through CREB-Binding Protein Mol. Cell. Biol., July 15, 2000; 20(14): 5048 - 5063. [Abstract] [Full Text]

				G. Ching and R. Liem Analysis of the roles of the head domains of type IV rat neuronal intermediate filament proteins in filament assembly using domain-swapped chimeric proteins J. Cell Sci., January 7, 1999; 112(13): 2233 - 2240. [Abstract] [PDF]

				J.-S. Qi, Y. Yuan, V. Desai-Yajnik, and H. H. Samuels Regulation of the mdm2 Oncogene by Thyroid Hormone Receptor Mol. Cell. Biol., January 1, 1999; 19(1): 864 - 872. [Abstract] [Full Text] [PDF]

				T. Palomino, A. Sánchez-pacheco, P. Peña, and A. Aranda A direct protein-protein interaction is involved in the cooperation between thyroid hormone and retinoic acid receptors and the transcription factor GHF-1 FASEB J, September 1, 1998; 12(12): 1201 - 1209. [Abstract] [Full Text]

				T. Tagami, P. Kopp, W. Johnson, O. K. Arseven, and J. L. Jameson The Thyroid Hormone Receptor Variant {alpha}2 Is a Weak Antagonist because It Is Deficient in Interactions with Nuclear Receptor Corepressors Endocrinology, May 1, 1998; 139(5): 2535 - 2544. [Abstract] [Full Text] [PDF]

				T. Tagami and J. L. Jameson Nuclear Corepressors Enhance the Dominant Negative Activity of Mutant Receptors That Cause Resistance to Thyroid Hormone Endocrinology, February 1, 1998; 139(2): 640 - 650. [Abstract] [Full Text] [PDF]

				G. Ching and R. Liem Roles of head and tail domains in alpha-internexin's self-assembly and coassembly with the neurofilament triplet proteins J. Cell Sci., January 2, 1998; 111(3): 321 - 333. [Abstract] [PDF]

				R. E. M. Scott, X. S. Wu-Peng, P. M. Yen, W. W. Chin, and D. W. Pfaff Interactions of Estrogen- and Thyroid Hormone Receptors on a Progesterone Receptor Estrogen Response Element (ERE) Sequence: a Comparison with the Vitellogenin A2 Consensus ERE Mol. Endocrinol., October 1, 1997; 11(11): 1581 - 1592. [Abstract] [Full Text]

				S. G. Ball, M. Ikeda, and W. W. Chin Deletion of the Thyroid Hormone {beta}1 Receptor Increases Basal and Triiodothyronine-Induced Growth Hormone Messenger Ribonucleic Acid in GH3 Cells Endocrinology, August 1, 1997; 138(8): 3125 - 3132. [Abstract] [Full Text] [PDF]

				F. Pernasetti, L. Caccavelli, C. Van de Weerdt, J. A. Martial, and M. Muller Thyroid Hormone Inhibits the Human Prolactin Gene Promoter by Interfering with Activating Protein-1 and Estrogen Stimulations Mol. Endocrinol., June 1, 1997; 11(7): 986 - 996. [Abstract] [Full Text]

				D. Sun, C. L. Leung, and R. K.H. Liem Phosphorylation of the High Molecular Weight Neurofilament Protein (NF-H) by Cdk5 and p35 J. Biol. Chem., June 14, 1996; 271(24): 14245 - 14251. [Abstract] [Full Text] [PDF]

				R. Alvarez, J. de Andrés, P. Yubero, O. Viñas, T. Mampel, R. Iglesias, M. Giralt, and F. Villarroya A Novel Regulatory Pathway of Brown Fat Thermogenesis J. Biol. Chem., March 10, 1995; 270(10): 5666 - 5673. [Abstract] [Full Text] [PDF]