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Endocrinology, doi:10.1210/en.2007-0535
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Endocrinology Vol. 148, No. 10 4803-4811
Copyright © 2007 by The Endocrine Society

Activation of Endoproteolytic Processing of Insulin-Like Growth Factor-II in Fetal, Early Postnatal, and Pregnant Rats and Persistence of Circulating Levels in Postnatal Life

Qing Qiu, Jin-Yi Jiang, Michael Bell, Benjamin K. Tsang and Andrée Gruslin

Hormones, Growth, and Development Program (Q.Q., J.-Y.J., M.B., B.K.T., A.G.), Ottawa Health Research Institute, Ottawa, Ontario, Canada K1Y 4E9; and Departments of Obstetrics and Gynaecology (A.G.) and Cellular and Molecular Medicine (B.K.T.), University of Ottawa, The Ottawa Hospital, Ottawa, Ontario, Canada K1H 8L6

Address all correspondence and requests for reprints to: Andrée Gruslin, Department of Obstetrics and Gynecology, The Ottawa Hospital, Ottawa, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6. E-mail: agruslin{at}ottawahospital.on.ca; or Qing Qiu, Ottawa Health Research Institute, Ottawa, Ontario, Canada K1Y 4E9. E-mail: qqiu{at}ohri.ca.

The process of posttranslational modifications of IGF-II likely has important physiological consequences. In addition to mature IGF-II, glycosylated proIGF-II(156-amino acid peptide) and two glycosylated big IGF-II forms, IGF-II(1–104) and IGF-II(1–87), have been identified in the human circulation. Due to lack of an appropriate methodology, different IGF-II isoforms have not been demonstrated and characterized in the rat circulation, thus preventing a better understanding of the physiological and pathological roles of IGF-II. In the present study, we characterized each IGF-II form and assessed its content in the rat circulation throughout life time by using a highly sensitive Western blot analysis, which is void of the IGF binding protein interference and distinguished all IGF-II forms. For the first time, we demonstrated the presence of IGF-II variants, including proIGF-II, IGF-II(1–87), and mature IGF-II, in the rat circulation during postnatal life, challenging the current impression that IGF-II is absent from sera of adult rats. ProIGF-II is glycosylated and is the predominant form in the rat circulation. Endoproteolytic processing of proIGF-II was clearly activated in fetal, neonatal, and pregnant rats, likely reflecting its involvement in fetal development through the generation of specific forms of IGF-II (e.g. mature IGF-II) that are required for their distinct biological functions. Taken together, our data also suggest that serum IGF-II profiles may reflect underlying physiological conditions.




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Copyright © 2007 by The Endocrine Society