Repression of vasopressin gene expression by glucocorticoids in transgenic mice: evidence of a direct mechanism mediated by proximal 5' flanking sequence

Neuroscience
Z D BurkeD Carter

Abstract

Glucocorticoids are known to exert multiple effects upon neuronal systems and neuronal gene expression but the molecular mechanisms through which these effects are mediated are largely undefined. In this study, a transgenic mouse model that expresses a bovine vasopressin transgene was used to investigate the mechanisms by which this neuropeptide gene is repressed by glucocorticoids. Using both northern analysis and a reverse transcriptase polymerase chain reaction assay, depletion of glucocorticoids with the 11,beta-hydroxylase inhibitor metyrapone was shown to result in a dexamethasone-reversed increase in ectopic adrenal transgene messenger RNA levels. This result shows that sequences within the confines of the 3.5 kb transgene are sufficient to mediate repression by glucocorticoids, and indicates the involvement of a type II glucocorticoid receptor mechanism which is independent of cellular context. Evidence for the involvement of cis-acting repressive elements in the proximal 5' flanking sequence was obtained in further studies in which bovine transgene constructs were shown to be negatively regulated by dexamethasone in 293 cells. The further demonstration that recombinant glucocorticoid receptor binds to a vasopressin pro...Continue Reading

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Citations

Oct 17, 2002·Frontiers in Neuroendocrinology·J Peter H Burbach
Dec 14, 2001·Biochemical and Biophysical Research Communications·J K KimR W Schrier
May 30, 2014·The Journal of Endocrinology·Dawn E W LivingstoneRuth Andrew
May 5, 2000·Experimental Physiology·W G North
Oct 30, 2004·Stress : the International Journal on the Biology of Stress·Simona VolpiGreti Aguilera
Sep 2, 1999·British Journal of Cancer·J M CoulsonP J Woll
Jan 1, 2008·Gene Regulation and Systems Biology·Masanori Yoshida
Jun 28, 2001·Physiological Reviews·J P BurbachH Gainer
Mar 7, 2002·American Journal of Physiology. Renal Physiology·James D Stockand
Apr 28, 2021·Peptides·Mitsuhiro YoshimuraYoichi Ueta

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