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A GH receptor antisense oligonucleotide inhibits hepatic GH receptor expression, lGF-I production and body weight gain in normal mice
Tachas, G., Lofthouse, S., Wraight, C. J., Baker, B. F., Sioufi, N. B., Jarres, R. A., Berdeja, A., Rao, A. M., Kerr, L. M., d'Aniello, E. M. and Waters, M. J. (2006) A GH receptor antisense oligonucleotide inhibits hepatic GH receptor expression, lGF-I production and body weight gain in normal mice. Journal of Endocrinology, 189 1: 147-154.
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| Author(s) |
Tachas, G.
Lofthouse, S.
Wraight, C. J.
Baker, B. F.
Sioufi, N. B.
Jarres, R. A.
Berdeja, A.
Rao, A. M.
Kerr, L. M.
d'Aniello, E. M.
Waters, M. J.
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| Title |
A GH receptor antisense oligonucleotide inhibits hepatic GH receptor expression, lGF-I production and body weight gain in normal mice
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| Journal name |
Journal of Endocrinology
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| Publication date |
2006
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| Volume number |
189
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| Issue number |
1
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| ISSN |
0022-0795
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| Start page |
147
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| End page |
154
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| Total pages |
8
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| Editor(s) |
J. R. E. Davis
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| Place of publication |
Bristol
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| Publisher |
Society of Endocrinology
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| Collection year |
2006
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| Language |
eng
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| Subject |
C1
321004 Endocrinology
730105 Endocrine organs and diseases (incl. diabetes)
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| Abstract |
Diabetic retinopathy and acromegaly are diseases associated with excess action of GH and its effector IGF-1, and there is a need for improved therapies. We have designed all optimised 2'-O-(2-methoxyethyl)-modified phosphorothioate oligodeoxynucleotide, ATL 227446, and demonstrated its ability to Suppress GH receptor mRNA in vitro. Subcutaneous injections of ATL 227446 reduced GH receptor mRNA levels, GH binding activity and serum IGF-1 levels in mice after seven days of closing. The reduction in serum IGF-1 could be sustained for over tell weeks of dosing at therapeutically relevant levels, during which there was also a significant decrease in body weight gain in antisense-treated mice relative to saline and mismatch control-treated mice. The findings indicate that administration of an antisense oligonucleotide to the GH receptor may be applicable to human diseases in which suppression of GH action provides therapeutic benefit.
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| Keyword(s) |
Endocrinology & Metabolism
Growth-hormone-receptor
Retinal Neovascularization
Phosphorothioate
Rats
Therapy
Analogs
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