Regulation of myo-inositol transport during the growth and differentiation of thyrocytes: a link with thyroid-stimulating hormone-induced phospholipase A2 activity.
The Vmax of myo-inositol transport increased 3-fold during epidermal growth factor (EGF)-induced growth and thyroid-stimulating hormone. (TSH)-induced differentiation in primary cultures of sheep and human thyrocytes. The Km remained unaltered. This up-regulation required the presence of insulin. The TSH-induced rise in myo-inositol transport commenced 8 to 16 h after the initial stimulus and achieved a plateau at 24 h. In human thyrocytes the change in Vmax was accompanied by an increase in the steady-state levels of mRNA for the myo-inositol transporter following treatment with either ligand. Examination of the metabolites of myo-inositol showed few significant changes after treatment of sheep thyrocytes with EGF for 24 h. This is consistent with maintenance of the intracellular concentration of myo-inositol as the cells enlarge in preparation for cell division. In TSH-treated cells, however, up-regulation of myo-inositol transport was linked with increased myo-inositol cycling across the cell membrane, increased phospholipase A2-mediated turnover of phosphatidylinositol and a concomitant increase in arachidonic acid turnover. Increased levels of myo-inositol phosphates were also noted 24 h after TSH treatment. These results indicate the initiation of secondary signalling events many hours after the primary stimulus.
Grafton
G
G
Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, UK.
Baxter
M A
MA
Sheppard
M C
MC
Eggo
M C
MC
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D016521:Electrophoresis, Gel, Pulsed-Field; D004790:Enzyme Induction; D004815:Epidermal Growth Factor / Q000494:pharmacology; D007294:Inositol / Q000096:biosynthesis / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D012756:Sheep; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology*
D002352:Carrier Proteins; D007328:Insulin; D016718:Arachidonic Acid; D007294:Inositol; D004815:Epidermal Growth Factor; D013972:Thyrotropin; D010741:Phospholipases A; D054467:Phospholipases A2