Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1991 Aug;88(2):385–389. doi: 10.1172/JCI115315

Glucocorticoids induce transcription and expression of the alpha 1B adrenergic receptor gene in DTT1 MF-2 smooth muscle cells.

M Sakaue 1, B B Hoffman 1
PMCID: PMC295342  PMID: 1650792

Abstract

Steroid hormones modulate physiological processes by a number of mechanisms including regulation of gene expression. We wondered if glucocorticoids might induce expression of alpha 1 adrenergic receptors, which could contribute to the increased sensitivity of vascular smooth muscle to catecholamines that may occur with glucocorticoid excess. We examined the effects of dexamethasone on the expression of the alpha 1B adrenergic receptor gene in DDT1 MF-2 smooth muscle cells. Dexamethasone (10(-6) M) produced a 1.8 +/- 0.2-fold increase in expression of alpha 1B receptors determined with [3H]prazosin. Steady-state values of alpha 1B adrenergic receptor mRNA, analyzed by Northern blotting, increased 2.8 +/- 0.7-fold after 48 h exposure to dexamethasone. This effect of dexamethasone occurred in the presence of the protein synthesis inhibitor cycloheximide. alpha 1B receptor mRNA abundance was also increased by testosterone and aldosterone, whereas beta estradiol and progesterone had no effect. The alpha 1B receptor gene transcription rate, determined in nuclear run-off assays, increased 2.6 +/- 0.6-fold in cells treated with dexamethasone for 24 h. The half-life of the alpha 1B receptor mRNA was unchanged by dexamethasone. These data indicate that glucocorticoids regulate expression of alpha 1B receptors by increasing the rate of transcription of this gene.

Full text

PDF
385

Images in this article

386Image
on p.386
386Image
on p.386
386Image
on p.386
387Image
on p.387

Selected References

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

  1. Beato M. Gene regulation by steroid hormones. Cell. 1989 Feb 10;56(3):335–344. doi: 10.1016/0092-8674(89)90237-7. [DOI] [PubMed] [Google Scholar]
  2. Besse J. C., Bass A. D. Potentiation by hydrocortisone of responses to catecholamines in vascular smooth muscle. J Pharmacol Exp Ther. 1966 Nov;154(2):224–238. [PubMed] [Google Scholar]
  3. Burnstein K. L., Cidlowski J. A. Regulation of gene expression by glucocorticoids. Annu Rev Physiol. 1989;51:683–699. doi: 10.1146/annurev.ph.51.030189.003343. [DOI] [PubMed] [Google Scholar]
  4. Cato A. C., Skroch P., Weinmann J., Butkeraitis P., Ponta H. DNA sequences outside the receptor-binding sites differently modulate the responsiveness of the mouse mammary tumour virus promoter to various steroid hormones. EMBO J. 1988 May;7(5):1403–1410. doi: 10.1002/j.1460-2075.1988.tb02957.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Collins S., Caron M. G., Lefkowitz R. J. Beta-adrenergic receptors in hamster smooth muscle cells are transcriptionally regulated by glucocorticoids. J Biol Chem. 1988 Jul 5;263(19):9067–9070. [PubMed] [Google Scholar]
  6. Collins S., Quarmby V. E., French F. S., Lefkowitz R. J., Caron M. G. Regulation of the beta 2-adrenergic receptor and its mRNA in the rat ventral prostate by testosterone. FEBS Lett. 1988 Jun 6;233(1):173–176. doi: 10.1016/0014-5793(88)81378-4. [DOI] [PubMed] [Google Scholar]
  7. Colucci W. S., Gimbrone M. A., Jr, McLaughlin M. K., Halpern W., Alexander R. W. Increased vascular catecholamine sensitivity and alpha-adrenergic receptor affinity in female and estrogen-treated male rats. Circ Res. 1982 Jun;50(6):805–811. doi: 10.1161/01.res.50.6.805. [DOI] [PubMed] [Google Scholar]
  8. Cornett L. E., Norris J. S. Characterization of the alpha 1-adrenergic receptor subtype in a smooth muscle cell line. J Biol Chem. 1982 Jan 25;257(2):694–697. [PubMed] [Google Scholar]
  9. Cotecchia S., Schwinn D. A., Randall R. R., Lefkowitz R. J., Caron M. G., Kobilka B. K. Molecular cloning and expression of the cDNA for the hamster alpha 1-adrenergic receptor. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7159–7163. doi: 10.1073/pnas.85.19.7159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Drubin D. G., Caput D., Kirschner M. W. Studies on the expression of the microtubule-associated protein, tau, during mouse brain development, with newly isolated complementary DNA probes. J Cell Biol. 1984 Mar;98(3):1090–1097. doi: 10.1083/jcb.98.3.1090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Greenberg M. E., Ziff E. B. Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature. 1984 Oct 4;311(5985):433–438. doi: 10.1038/311433a0. [DOI] [PubMed] [Google Scholar]
  12. Groner B., Hynes N. E., Rahmsdorf U., Ponta H. Transcription initiation of transfected mouse mammary tumor virus LTR DNA is regulated by glucocorticoid hormones. Nucleic Acids Res. 1983 Jul 25;11(14):4713–4725. doi: 10.1093/nar/11.14.4713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gunning P., Ponte P., Okayama H., Engel J., Blau H., Kedes L. Isolation and characterization of full-length cDNA clones for human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed. Mol Cell Biol. 1983 May;3(5):787–795. doi: 10.1128/mcb.3.5.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hadcock J. R., Malbon C. C. Regulation of beta-adrenergic receptors by "permissive" hormones: glucocorticoids increase steady-state levels of receptor mRNA. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8415–8419. doi: 10.1073/pnas.85.22.8415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Haigh R. M., Jones C. T. Effect of glucocorticoids on alpha 1-adrenergic receptor binding in rat vascular smooth muscle. J Mol Endocrinol. 1990 Aug;5(1):41–48. doi: 10.1677/jme.0.0050041. [DOI] [PubMed] [Google Scholar]
  16. Ham J., Thomson A., Needham M., Webb P., Parker M. Characterization of response elements for androgens, glucocorticoids and progestins in mouse mammary tumour virus. Nucleic Acids Res. 1988 Jun 24;16(12):5263–5276. doi: 10.1093/nar/16.12.5263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Han C., Abel P. W., Minneman K. P. Alpha 1-adrenoceptor subtypes linked to different mechanisms for increasing intracellular Ca2+ in smooth muscle. Nature. 1987 Sep 24;329(6137):333–335. doi: 10.1038/329333a0. [DOI] [PubMed] [Google Scholar]
  18. Jazayeri A., Meyer W. J., 3rd Glucocorticoid modulation of beta-adrenergic receptors of cultured rat arterial smooth muscle cells. Hypertension. 1988 Oct;12(4):393–398. doi: 10.1161/01.hyp.12.4.393. [DOI] [PubMed] [Google Scholar]
  19. Kadowitz P. J., Yard A. C. Influence of hydrocortisone on cardiovascular responses to epinephrine. Eur J Pharmacol. 1971;13(3):281–286. doi: 10.1016/0014-2999(71)90215-9. [DOI] [PubMed] [Google Scholar]
  20. Minneman K. P. Alpha 1-adrenergic receptor subtypes, inositol phosphates, and sources of cell Ca2+. Pharmacol Rev. 1988 Jun;40(2):87–119. [PubMed] [Google Scholar]
  21. Norris J. S., Garmer D. J., Brown F., Popovich K., Cornett L. E. Characteristics of an adenylate cyclase coupled beta 2-adrenergic receptor in a smooth muscle tumor cell line. J Recept Res. 1983;3(5):623–645. doi: 10.3109/10799898309041951. [DOI] [PubMed] [Google Scholar]
  22. Norris J. S., Gorski J., Kohler P. O. Androgen receptors in a Syrian hamster ductus deferens tumour cell line. Nature. 1974 Mar 29;248(447):422–424. doi: 10.1038/248422a0. [DOI] [PubMed] [Google Scholar]
  23. Norris J. S., Kohler P. O. Syrian hamster glucocorticoid receptors. Characteristics of binding of partially purified receptor to DNA. J Biol Chem. 1983 Feb 25;258(4):2350–2356. [PubMed] [Google Scholar]
  24. Palmiter R. D., Carey N. H. Rapid inactivation of ovalbumin messenger ribonucleic acid after acute withdrawal of estrogen. Proc Natl Acad Sci U S A. 1974 Jun;71(6):2357–2361. doi: 10.1073/pnas.71.6.2357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Peterson G. L. A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal Biochem. 1977 Dec;83(2):346–356. doi: 10.1016/0003-2697(77)90043-4. [DOI] [PubMed] [Google Scholar]
  26. Ringold G. M. Steroid hormone regulation of gene expression. Annu Rev Pharmacol Toxicol. 1985;25:529–566. doi: 10.1146/annurev.pa.25.040185.002525. [DOI] [PubMed] [Google Scholar]
  27. Rodgers J. R., Johnson M. L., Rosen J. M. Measurement of mRNA concentration and mRNA half-life as a function of hormonal treatment. Methods Enzymol. 1985;109:572–592. doi: 10.1016/0076-6879(85)09116-9. [DOI] [PubMed] [Google Scholar]
  28. Saruta T., Suzuki H., Handa M., Igarashi Y., Kondo K., Senba S. Multiple factors contribute to the pathogenesis of hypertension in Cushing's syndrome. J Clin Endocrinol Metab. 1986 Feb;62(2):275–279. doi: 10.1210/jcem-62-2-275. [DOI] [PubMed] [Google Scholar]
  29. Schwinn D. A., Lomasney J. W., Lorenz W., Szklut P. J., Fremeau R. T., Jr, Yang-Feng T. L., Caron M. G., Lefkowitz R. J., Cotecchia S. Molecular cloning and expression of the cDNA for a novel alpha 1-adrenergic receptor subtype. J Biol Chem. 1990 May 15;265(14):8183–8189. [PubMed] [Google Scholar]
  30. Yamamoto K. R. Steroid receptor regulated transcription of specific genes and gene networks. Annu Rev Genet. 1985;19:209–252. doi: 10.1146/annurev.ge.19.120185.001233. [DOI] [PubMed] [Google Scholar]
  31. Yard A. C., Kadowitz P. J. Studies on the mechanism of hydrocortisone potentiation of vasoconstrictor responses to epinephrine in the anesthetized animal. Eur J Pharmacol. 1972 Oct;20(1):1–9. doi: 10.1016/0014-2999(72)90209-9. [DOI] [PubMed] [Google Scholar]
  32. von der Ahe D., Janich S., Scheidereit C., Renkawitz R., Schütz G., Beato M. Glucocorticoid and progesterone receptors bind to the same sites in two hormonally regulated promoters. Nature. 1985 Feb 21;313(6004):706–709. doi: 10.1038/313706a0. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES