Identification of <i>M</i><sub>r</sub> variants of proclatin with monoclonal antibodies

Aston, R.; Young, Kung Chia; Berg, Henk van den; Iványi, Juraj

doi:10.1016/0014-5793(84)80486-x

Cited by 10 publications

(3 citation statements)

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“…Antibodies to the COOHterminal fragment (7kDa) of hGH were raised in Balbk mice by immunization with Freund's complete adjutant. The preparation of this fragment from hGH has been described previously (Aston & Ivanyi, 1983). Antiserum to IGF-I (549/804) was raised in rabbits and was provided as a gift from NIADDK (London).…”

Section: Methodsmentioning

confidence: 99%

“…Binding of 1251-labelled bGH or 1251-labelled hGH to microsome receptors, in the presence of various doses of different MAbs, was expressed as a percentage of the total specific binding, which was measured by displacement of tracer in the presence of excess 104unlabelled hormone. Determination of 1251-labelled hGH binding to IM9 cells and the effects of MAbs on NB2 cell proliferation has been described previously (Aston & Ivanyi, 1983;Ivanyi, 1982).…”

Section: Methodsmentioning

confidence: 99%

“…Polyclonal antisera raised against the COOH-terminal, subtilisin-derived fragment of hGH (Aston & Ivanyi, 1983) were found to bind to intact hGH and enhance its activity in dwarf mice (Fig. 2).…”

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confidence: 99%

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Enhancement of growth hormone activity in vivo by monoclonal antibodies: potential for autoimmunization

et al. 1988

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Enhancement of hormonal activity by monoclonal antibodies (MAbs) or polyclonal antisera has been observed in a number of systems both in vitro and in vivo. The short biological half-life of many hormones or mediators is, in itself, suggestive that prolongation of activity in the circulation would enhance activity. Indeed, during the course of insulin therapy in diabetes the development of antibodies against the hormone is often associated with an improvement in hormone activity ("depot effect") which, in some cases, appears to be beneficial to the patient. Similarly, in patients who develop antibodies whilst receiving human growth hormone (hGH) therapy, only a small proportion (5%) suffer a decreased growth rate (Ammann, 1986). Antibody-mediated enhancement of insulin activity in vitro has been achieved by virtue of the bivalent nature of antibody molecules (Schecter er al. 1!379a), indicating that the same hormone may have its activity enhanced by distinct mechanisms. A similar antibody-mediated enhancement effect was also observed for epidermal growth-factor activity in vitro (Schecter et al. 19796). In both cases the enhancement effect was attributed to facilitated cross-linking of the corresponding receptor through the hormone molecule, implying that the specificity of the antiserum employed must be such that hormone-receptor interaction is permitted.Enhancement of hGH and bovine growth hormone (bGH) activity in vivo (as measured by increased growth, cartilage metabolism, and muscle protein synthesis) has been demonstrated using hormone-MAb complexes (Holder et al. 1985; Aston et al. 1986,1987). The efficacy of the effect appears to depend on the specificity of the MAb in question; however, to date no MAb used alone has inhibited the growth-promoting activity of growth hormone (GH) in vivo. This effect is independent of MAb bivalency or antibody Fc-region-mediated targeting to the liver (Aston et al. 1986,1987).Wool-growth responses in ewes treated with ox GH were increased in animals showing antibodies to the hormone; it was proposed that decreased hormone degradation was responsible for this increased activity (Ferguson, 1954). Furthermore, improvements in GH potency in vivo have also been noted when GH is administered in a prolonged or continuous fashion, rather than in a single treatment (Clark et al. 1985).In addition to enhancement of the somatogenic activity of hGH and bGH, MAbs have also been shown to enhance the lactogenic actions of hGH and human chorionic somatomammotrophin ( h a ) . We describe here the effects of anti-hGH and bGH MAbs as well as the binding of polyclonal antisera directed towards the carboxyl-terminal region of hGH on growth rate. It is shown that there is no clear correlation between the effects of different MAbs on hormone-receptor binding and the growth-enhancement

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%