REGULATION OF MYOINOSITOL TRANSPORT DURING THE GROWTH AND DIFFERENTIATION OF THYROCYTES - A LINK WITH THYROID-STIMULATING HORMONE-INDUCED PHOSPHOLIPASE A(2) ACTIVITY

The V-max. of myo-inositol transport increased 3-fold during epidermal growth factor (EGF)-induced growth and thyroid-stimulating hormone (T SH)-induced differentiation in primary cultures of sheep and human thy rocytes. The K-m remained unaltered. This up-regulation required the p resence of insulin. The TSH-induced rise in myo-inositol transport com menced 8 to 16 h after the initial stimulus and achieved a plateau at 24 h. In human thyrocytes the change in V-max. was accompanied by an i ncrease in the steady-state levels of mRNA for the myo-inositol transp orter following treatment with either ligand. Examination of the metab olites of mya-inositol showed few significant changes after treatment of sheep thyrocytes with EGF for 24 h. This is consistent with mainten ance of the intracellular concentration of myo-inositol as the cells e nlarge in preparation for cell division. In TSH-treated cells, however , up-regulation of myo-inositol transport was linked with increased my o-inositol cycling across the cell membrane, increased phospholipase A (2)-mediated turnover of phosphatidylinositol and a concomitant increa se in arachidonic acid turnover. Increased levels of myo-inositol phos phates were also noted 24 h after TSH treatment. These results indicat e the initiation of secondary signalling events many hours after the p rimary stimulus.