13 research outputs found

    A GH receptor antisense oligonucleotide inhibits hepatic GH receptor expression, lGF-I production and body weight gain in normal mice

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    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

    New insights into growth hormone receptor function and clinical implications

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    Although used as a therapeutic for 50 years, it is only recently that the application of molecular techniques has provided a basis for understanding growth hormone's (GH) clinical actions. This article reviews progress in our current knowledge of the molecular mechanism of growth hormone (GH) receptor activation based on a number of physicochemical techniques, and documents insights gained into the means used by the activated GH receptor to control the expression of genes regulating growth and metabolism. These findings are related to disorders of short stature, and the therapeutic consequences are summarized
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