|Budget Amount *help
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1989: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1988: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1987: ¥2,400,000 (Direct Cost: ¥2,400,000)
Proteoglyean is a macromolecule consisting of glycosaminoglycan chains covalently linked with core-glycoprotein. It is important as a ground substance in cell-culture system such as chondrocytes or osteogenic cells. The synthesis is influenced by hormone in granulosa cells.
However, what kind of roles the proteoglyean does play in thyroid tissue in which particular secretory process is operating remain unanswered. In the present study, we have disclosed followings;
1. Proteoglycan production in thyroid cells is closely related to the cell proliferation through cAMP dependent mechanism (Shishiba Y, et al. J Biol Chem 263:1745, 1988).
2. Proteoglycan was also produced in thyroid organ culture system. Chondroitin sulfate proteoglyean was secreted into medium in a fashion dependent to the dose of TSH, while heparan sulfste proteoglyean remained in the tissue. From the autoradiography of ^<35>S, the kinetics of ^<35>S grain resembled those of thyroglobulin. It was speculated that proteoglyeans
were produced in epithelial cells, secreted into follicular space and concentrated. Proteoglyeans may function as a mechanical support for the follicular structure in thyroid tissue, as well as in ovary (Shishiba Y, et al. Progress in Thyroidology 1989, p.259, Korea).
3. Apart from thyroid tissue, proteoglycan production in fibroblast culture was enhanced by IgG's of Graves' disease with pretibial myxedema. T_3 excess also favors the,synthesis of proteoglycan. The cause of pretibial myxedema is thus the accumulation of proteoglycan produced by fibroblasts stimulated by IgG's and T_3 excess. Whether the same story can be applied to the pathogenesis of malignant exophthalmos in Graves' disease is under study (Shishiba Y, et al. The Thyroid P-385, 1988).
4. Proteoglyeans are the regulator of calcification in osteogenic cell culture. In early phase of culture where calcification was not observed, osteogenic cells produced large chondroitin sulfate proteoglyean, small chondroitin sulfate proteoglycan, haparan sulfate proteoglyean and hyaluronic acids. in the calcification phase of culture, the production of these proteoglycan species was decreased dramatically. 1,25(OH)_2D_3, which enhanced calcification, decreased proteoglyean production and accelerated degradation by increasing proteoglyean binding to the receptor. Thus, proteoglyeans are one of the factors to inhibit calcification by occupying the gap junction of collagen fibers. When the production of proteoglyeans is decreased either by aging or by 1,25(OH)_2D_3, calcification starts in the unoccupied gap junction. Less