This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wang, J. Articles by Lewitt, M. S. Search for Related Content PubMed PubMed Citation Articles by Wang, J. Articles by Lewitt, M. S.

Gender-Specific Pattern of Insulin-Like Growth Factor-Binding Protein-3 Protease Activity in Mouse Thyroid

Department of Molecular Medicine, Karolinska Institute, Stockholm S-171 76, Sweden

Address all correspondence and requests for reprints to: Moira S. Lewitt, Karolinska Institutet, Department of Molecular Medicine, Karolinska Hospital, M1:02, Stockholm S-171 76, Sweden. E-mail: Moira.Lewitt{at}molmed.ki.se.

There is evidence that the IGF system plays an important role in the growth and function of the thyroid gland. Proteolysis is an important posttranslational process that modulates the affinity of IGF binding proteins (IGFBPs) to IGFs, thus regulating their activity. IGFBP-3 has been shown to be cleaved by members of the kallikrein family, some of which are expressed in human thyroid and are characterized by regulation by steroid hormones. The aim of this study was to determine whether IGFBP-3 protease activity is present in mouse thyroid tissue and to characterize its activity by gender and nutrition. Male and female BALB/c mice, aged 16 wk, were studied in the fasted state, or after 1-h or 4-h refeeding. IGFBP protease activity was present in thyroid tissue and resulted in a decrease in IGFBP-3 affinity for IGF-I. The activity was inhibited by 10 mM ZnCl₂, activated by CaCl₂, and was substantially greater in tissue from male mice compared with that from female animals. These properties and the pattern of effect of a panel of protease inhibitors were consistent with this protease being a member of the tissue kallikrein family. Serum inhibited the proteolytic effect of thyroid extracts. There was no effect of nutrition. In conclusion, the degree of activity of IGFBP-3 protease in mouse thyroid tissue is gender specific and is likely to lead to an increased IGF availability in male mice.