Insulin-like growth factor I stimulates inositol phosphate accumulation, a rise in cytoplasmic free calcium, and proliferation in cultured porcine thyroid cells.
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.
Takasu
N
N
Department of Gerontology, Endocrinology and Metabolism, School of Medicine, Shinshu University, Nagano-ken, Japan.
Takasu
M
M
Komiya
I
I
Nagasawa
Y
Y
Asawa
T
T
Shimizu
Y
Y
Yamada
T
T
D000818:Animals; D001572:Benzofurans; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D016257:Fura-2; D007295:Inositol Phosphates / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D013002:Somatomedins / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D013552:Swine; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D001572:Benzofurans; D005456:Fluorescent Dyes; D007295:Inositol Phosphates; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D002118:Calcium; D016257:Fura-2