Abstract
Insulin-like growth factor (IGF-I) stimulates thyroid cell proliferation. Using primary cultured porcine thyroid cells, we studied the intracellular pathways that mediate the action of IGF-I on thyroid cell proliferation. IGF-I stimulates inositol phosphate accumulation, a rise in cytoplasmic free calcium [( Ca2+]i), and cell proliferation. Exposure to IGF-I results in a time- and dose-dependent accumulation of inositol monophosphate, inositol bisphosphate, and inositol trisphosphate. IGF-I also increases [Ca2+]i, measured using fura-2, a fluorescent Ca2+ indicator; the IGF-I-induced [Ca2+]i response occurs immediately, reaches a maximum within 1 min, and then slowly declines. IGF-I stimulates thyroid cell proliferation, stimulates thymidine incorporation, and increases cell numbers. The IGF-I-induced inositol phosphate accumulation and [Ca2+]i response parallel thyroid cell proliferation in a dose-dependent manner; the maximal response is observed at a concentration of 100 ng/ml IGF-I, with half-maximal stimulation at approximately 10 ng/ml. Inositol phosphate accumulation and [Ca2+]i response after IGF-I stimulation may function as intracellular messengers for thyroid cell proliferation. This report may constitute the first demonstration of IGF-I-stimulated inositol phosphate accumulation and [Ca2+]i response in the cells.
Highlights
IntroductionUsing primary cultured porcine thyroid cells, we studied the intracellular pathways that mediate the action of IGF-I on thyroid cell proliferation
These data suggest that inositol phosphate accumulation and [Ca2+]iresponse may function as intracellular messengers for IGF-I-stimulated thyroid cell proliferation
One hundred ng/ml IGF-I increased inositol monophosphate (IP,)(Fig. 1,C and F ) .In theabsence of LiC1, IP1levels reached a maximum at about 5 min and remained nearly constant atapproximately twice the basal levels
Summary
Using primary cultured porcine thyroid cells, we studied the intracellular pathways that mediate the action of IGF-I on thyroid cell proliferation. Insulin-like growth factorI (IGF-I),’ a growth hormonedependent serum growth factor, stimulates proliferation of porcine thyroid cells in primary culture [1].we do not know much about the intracellular pathways that mediate the action of IGF-I on thyroid cell proliferation. Epidermal growth factor (EGF), which stimulates thyroid cell proliferation, increases cytoplasmic free calcium ([Ca”Ii), indicating that [Ca2+Iiis a possible mediator of. We report here that IGF-I leads to an accumulation of inositol phosphates and induces an increase in [Ca2+]i.IGF-I stimulates thyroid cell proliferation. These data suggest that inositol phosphate accumulation and [Ca2+]iresponse may function as intracellular messengers for IGF-I-stimulated thyroid cell proliferation
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