Gender-specific pattern of insulin-like growth factor-binding protein-3 protease activity in mouse thyroid.
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 ZnCl(2), activated by CaCl(2), 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.
Wang
Jing
J
Department of Molecular Medicine, Karolinska Institute, Stockholm S-171 76, Sweden.
Grünler
Jacob
J
Lewitt
Moira S
MS
D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D004435:Eating; D010450:Endopeptidases / Q000378:metabolism*; D005215:Fasting; D005260:Female; D006031:Glycosylation; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size; D012727:Sex Characteristics; D013002:Somatomedins / Q000378:metabolism; D013961:Thyroid Gland / Q000033:anatomy & histology / Q000201:enzymology*
D018972:Insulin-Like Growth Factor Binding Protein 3; D013002:Somatomedins; D010450:Endopeptidases; C080473:insulin-like growth factor binding protein-3 protease