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.


Author 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.
Title A GH receptor antisense oligonucleotide inhibits hepatic GH receptor expression, lGF-I production and body weight gain in normal mice
Journal name Journal of Endocrinology   Check publisher's open access policy
ISSN 0022-0795
Publication date 2006
Sub-type Article (original research)
DOI 10.1677/joe.1.06553
Volume 189
Issue 1
Start page 147
End page 154
Total pages 8
Editor J. R. E. Davis
Place of publication Bristol
Publisher Society of Endocrinology
Collection year 2006
Language eng
Subject C1
321004 Endocrinology
730105 Endocrine organs and diseases (incl. diabetes)
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.
Keyword Endocrinology & Metabolism
Growth-hormone-receptor
Retinal Neovascularization
Phosphorothioate
Rats
Therapy
Analogs
Q-Index Code C1

 
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