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. 1988 Jul;85(13):4755–4759. doi: 10.1073/pnas.85.13.4755

Identification of rat growth hormone genomic sequences targeting pituitary expression in transgenic mice.

S A Lira 1, E B Crenshaw 3rd 1, C K Glass 1, L W Swanson 1, M G Rosenfeld 1
PMCID: PMC280514  PMID: 3387436

Abstract

Constructs containing different segments of the 5' flanking region of the rat growth hormone gene fused to the human growth hormone coding sequences were introduced into fertilized mouse oocytes. As few as 181 base pairs of the rat growth hormone promoter targeted reporter gene expression to the pituitary gland of the resulting transgenic mice. A construct containing only 45 base pairs of the promoter failed to target expression of the reporter to the pituitary, indicating that the pituitary expression is directed by information contained in the segment spanning positions -181 to -45. In the pituitary, immunohistochemistry showed transgene expression mainly in the growth hormone-producing cells (somatotrophs), in a subset of cells producing thyrotropin, and occasionally in prolactin-producing cells. These data establish that cis-active elements contained within the first 180 base pairs of the promoter are sufficient for transcriptional activation of the growth hormone gene in somatotrophs and suggest a functional relationship among growth hormone, prolactin, and thyrotropin gene activation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barta A., Richards R. I., Baxter J. D., Shine J. Primary structure and evolution of rat growth hormone gene. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4867–4871. doi: 10.1073/pnas.78.8.4867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Casanova J., Copp R. P., Janocko L., Samuels H. H. 5'-Flanking DNA of the rat growth hormone gene mediates regulated expression by thyroid hormone. J Biol Chem. 1985 Sep 25;260(21):11744–11748. [PubMed] [Google Scholar]
  3. Cattini P. A., Peritz L. N., Anderson T. R., Baxter J. D., Eberhardt N. L. The 5'-flanking sequences of the human growth hormone gene contain a cell-specific control element. DNA. 1986 Dec;5(6):503–509. doi: 10.1089/dna.1.1986.5.503. [DOI] [PubMed] [Google Scholar]
  4. Crew M. D., Spindler S. R. Thyroid hormone regulation of the transfected rat growth hormone promoter. J Biol Chem. 1986 Apr 15;261(11):5018–5022. [PubMed] [Google Scholar]
  5. Dada M. O., Campbell G. T., Blake C. A. Pars distalis cell quantification in normal adult male and female rats. J Endocrinol. 1984 Apr;101(1):87–94. doi: 10.1677/joe.0.1010087. [DOI] [PubMed] [Google Scholar]
  6. Frawley L. S., Boockfor F. R., Hoeffler J. P. Identification by plaque assays of a pituitary cell type that secretes both growth hormone and prolactin. Endocrinology. 1985 Feb;116(2):734–737. doi: 10.1210/endo-116-2-734. [DOI] [PubMed] [Google Scholar]
  7. Glass C. K., Franco R., Weinberger C., Albert V. R., Evans R. M., Rosenfeld M. G. A c-erb-A binding site in rat growth hormone gene mediates trans-activation by thyroid hormone. Nature. 1987 Oct 22;329(6141):738–741. doi: 10.1038/329738a0. [DOI] [PubMed] [Google Scholar]
  8. Hammer R. E., Palmiter R. D., Brinster R. L. Partial correction of murine hereditary growth disorder by germ-line incorporation of a new gene. Nature. 1984 Sep 6;311(5981):65–67. doi: 10.1038/311065a0. [DOI] [PubMed] [Google Scholar]
  9. Larsen P. R., Harney J. W., Moore D. D. Repression mediates cell-type-specific expression of the rat growth hormone gene. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8283–8287. doi: 10.1073/pnas.83.21.8283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lefevre C., Imagawa M., Dana S., Grindlay J., Bodner M., Karin M. Tissue-specific expression of the human growth hormone gene is conferred in part by the binding of a specific trans-acting factor. EMBO J. 1987 Apr;6(4):971–981. doi: 10.1002/j.1460-2075.1987.tb04847.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Linzer D. I., Talamantes F. Nucleotide sequence of mouse prolactin and growth hormone mRNAs and expression of these mRNAs during pregnancy. J Biol Chem. 1985 Aug 15;260(17):9574–9579. [PubMed] [Google Scholar]
  12. Maniatis T., Goodbourn S., Fischer J. A. Regulation of inducible and tissue-specific gene expression. Science. 1987 Jun 5;236(4806):1237–1245. doi: 10.1126/science.3296191. [DOI] [PubMed] [Google Scholar]
  13. Nelson C., Albert V. R., Elsholtz H. P., Lu L. I., Rosenfeld M. G. Activation of cell-specific expression of rat growth hormone and prolactin genes by a common transcription factor. Science. 1988 Mar 18;239(4846):1400–1405. doi: 10.1126/science.2831625. [DOI] [PubMed] [Google Scholar]
  14. Nelson C., Crenshaw E. B., 3rd, Franco R., Lira S. A., Albert V. R., Evans R. M., Rosenfeld M. G. Discrete cis-active genomic sequences dictate the pituitary cell type-specific expression of rat prolactin and growth hormone genes. Nature. 1986 Aug 7;322(6079):557–562. doi: 10.1038/322557a0. [DOI] [PubMed] [Google Scholar]
  15. Nikitovitch-Winer M. B., Atkin J., Maley B. E. Colocalization of prolactin and growth hormone within specific adenohypophyseal cells in male, female, and lactating female rats. Endocrinology. 1987 Aug;121(2):625–630. doi: 10.1210/endo-121-2-625. [DOI] [PubMed] [Google Scholar]
  16. Palmiter R. D., Brinster R. L. Germ-line transformation of mice. Annu Rev Genet. 1986;20:465–499. doi: 10.1146/annurev.ge.20.120186.002341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Palmiter R. D., Chen H. Y., Brinster R. L. Differential regulation of metallothionein-thymidine kinase fusion genes in transgenic mice and their offspring. Cell. 1982 Jun;29(2):701–710. doi: 10.1016/0092-8674(82)90186-6. [DOI] [PubMed] [Google Scholar]
  18. Peterson G. L. Determination of total protein. Methods Enzymol. 1983;91:95–119. doi: 10.1016/s0076-6879(83)91014-5. [DOI] [PubMed] [Google Scholar]
  19. Roux M., Bartke A., Dumont F., Dubois M. P. Immunohistological study of the anterior pituitary gland - pars distalis and pars intermedia - in dwarf mice. Cell Tissue Res. 1982;223(2):415–420. doi: 10.1007/BF01258498. [DOI] [PubMed] [Google Scholar]
  20. Shields D., Blobel G. Cell-free synthesis of fish preproinsulin, and processing by heterologous mammalian microsomal membranes. Proc Natl Acad Sci U S A. 1977 May;74(5):2059–2063. doi: 10.1073/pnas.74.5.2059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Swanson L. W., Sawchenko P. E., Rivier J., Vale W. W. Organization of ovine corticotropin-releasing factor immunoreactive cells and fibers in the rat brain: an immunohistochemical study. Neuroendocrinology. 1983;36(3):165–186. doi: 10.1159/000123454. [DOI] [PubMed] [Google Scholar]
  22. West B. L., Catanzaro D. F., Mellon S. H., Cattini P. A., Baxter J. D., Reudelhuber T. L. Interaction of a tissue-specific factor with an essential rat growth hormone gene promoter element. Mol Cell Biol. 1987 Mar;7(3):1193–1197. doi: 10.1128/mcb.7.3.1193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ye Z. S., Samuels H. H. Cell- and sequence-specific binding of nuclear proteins to 5'-flanking DNA of the rat growth hormone gene. J Biol Chem. 1987 May 5;262(13):6313–6317. [PubMed] [Google Scholar]

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