Glucocorticoid regulation of human growth hormone expression in transgenic mice and transiently transfected cells

• Published in: Journal of endocrinology Vol. 122; no. 1; pp. 49 - 60
• Main Authors: SELDEN, R. F, YUN, J. S, MOORE, D. D, ROWE, M. E, MALIA, M. A, WAGNER, T. E, GOODMAN, H. M
• Format: Journal Article
• Language: English
• Published: Colchester BioScientifica 01.07.1989; Portland Press
• Subjects: Animals; Biological and medical sciences; Cloning, Molecular; Dexamethasone - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Growth Hormone - blood; Growth Hormone - genetics; Hormones and neuropeptides. Regulation; Hypothalamus. Hypophysis. Epiphysis. Urophysis; L Cells (Cell Line); Metallothionein - genetics; Mice; Mice, Transgenic; RNA, Messenger - drug effects; Transfection; Triamcinolone - pharmacology; Vertebrates: endocrinology; Cell culture; Dexamethasone; Nucleotide sequence; Steroid hormone; STH; Rodentia; Transgenic animal; Glucocorticoid; Protein hormone; Vertebrata; Mammalia; Synthetic product; Messenger RNA; Adenohypophyseal hormone; Mouse; DNA; Blotting assay; Radioimmunoassay; Hormonal regulation; Southern blotting
• ISSN: 0022-0795; 1479-6805
• DOI: 10.1677/joe.0.1220049

ABSTRACT A mouse metallothionein-I/human growth hormone fusion gene was microinjected into fertilized mouse eggs, the embryos were implanted into pseudopregnant foster mothers, and the offspring analysed. Five of twenty-six mice born after one series of injections contained from one to eight copies of the fusion gene stably integrated into their genomes and had human growth hormone in their serum. When several of these transgenic mice and transgenic offspring were treated with glucocorticoids, serum growth hormone levels were elevated from 1·5- to 6·3-fold. A fourfold induction in fusion gene mRNA in the liver of one of the five mice was also observed after treatment with glucocorticoids. When the fusion gene was transiently transfected into mouse L cells, dexamethasone caused a three- to fourfold induction of fusion gene mRNA and secreted human growth hormone. A deletion analysis of regulatory elements required for inducibility in L cells shows that DNA sequences responsible for the observed inductions are located within the transcribed region of the human growth hormone gene. However, a previously described glucocorticoid receptor binding site in the first intron of the gene is not required for response to the hormone. Journal of Endocrinology (1989) 122, 49–60