Insulin-like growth factor I: a mitogen for rat Schwann cells in the presence of elevated levels of cyclic AMP.
To develop effective procedures for improving the regeneration of peripheral nerves and for preventing the formation of neurofibromas, it is necessary to identify the different mitogens that stimulate the proliferation of Schwann cells. Insulin-like growth factor I (IGF-I), which is a potent autocrine growth factor in many tissues, is synthesized by proliferating Schwann cells. However, the role of IGF-I in stimulating their division is still uncertain. Here we show that nanomolar concentrations of IGF-I stimulate the growth of Schwann cells in primary culture. IGF-I alone was uneffective, but in the presence of forskolin (5 microM) or dibutyryl cyclic AMP (dbcAMP, 10 microM), it became a potent mitogen. Neither IGF-II nor epidermal growth factor (EGF) were effective even in the presence of forskolin. Insulin also stimulated Schwann cell proliferation in the presence of forskolin, but only at micromolar concentration. Receptors for IGF-I were visualized on the Schwann cell surface by indirect immunofluorescence staining using anti-human IGF-I receptor antibodies. Their presence was also assessed by binding assays using [125I]-IGF-I as a ligand. Scatchard analysis showed a single class of high-affinity receptors (Kd = 1.5 nM). Competitions studies with unlabeled IGF-I or insulin indicated a half-maximal displacement of [125I]-IGF-I by IGF-I at about 5 nM, while insulin was about 500-fold less effective. The number of binding sites for IGF-I was increased by exposing cells for 3 days to forskolin (-forskolin: about 5,100; + forskolin: about 12,200 binding sites/cell).(ABSTRACT TRUNCATED AT 250 WORDS)
Schumacher
M
M
Lab. Hormones, INSERM U33 Le Kremlin-Bicêtre, France.
Jung-Testas
I
I
Robel
P
P
Baulieu
E E
EE
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008934:Mitogens / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000187:drug effects / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects*; D012584:Sciatic Nerve / Q000166:cytology / Q000187:drug effects
D007328:Insulin; D008934:Mitogens; D007334:Insulin-Like Growth Factor I; D000242:Cyclic AMP; D017526:Receptor, IGF Type 1