Interactions of Insulin-Like Growth Factor-I (IGF-I) with Multiple Signal Transduction Pathways in FRTL5 Thyroid Follicular Cells
Insulin-like growth factor-I (IGF-I) binds to a specific cell surface receptor that displays intrinsic tyrosine kinase activity (1). The type I IGF receptor is activated by autophosphorylation of its beta subunit, however the postreceptor pathways involved in IGF-I stimulated DNA synthesis have not been elucidated completely. The IGFs classically act on mesenchymal tissue to promote cell growth and differentiated function (2), however studies of IGF action on endocrine epithelial cells have been relatively limited. In rat and porcine ovarian granulosa cells, IGF-I synergizes with FSH to enhance progesterone synthesis and LH receptor upregulation (3–6). This synergy occurs through IGF-I’s ability to potentiate FSH-stimulated cAMP accumulation (7). IGF-I by itself does not stimulate adenylate cyclase. Ovarian granulosa cells also have been demonstrated to secrete IGFs that appear to act as autocrine growth (or differentiation) factors (8). The rat thyroid follicular cell line, FRTL5, is another example of endocrine tissue of epithelial origin which responds to IGF-I (and to a lesser extent IGF-II and insulin) by increasing DNA synthesis and cell proliferation. In FRTL5 cells, the pituitary glycoprotein thyrotropin (TSH) acts both to stimulate thyroid differentiated function and cellular metabolism and replication (9). Thus, for FRTL5, TSH is a tissue specific mitogen.
KeywordsThyroid Follicular Cell Dibutyryl cAMP FRTL5 Cell Ovarian Granulosa Cell cAMP Generation
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