Transforming growth factor-alpha with insulin induces proliferation in rat utricular extrasensory epithelia

Hair cell loss in the human inner ear leads to sensorineural hearing loss and vestibular dysfunction. Recent studies suggest that exogenous addition of growth factors, for example, transforming growth factor-alpha with insulin, may stimulate the production of new supporting cells and hair cells in the mature mammalian vestibular sensory epithelium. Before any growth factor can be seriously considered for the treatment of clinical problems related to hair cell loss, its effects on the extrasensory epithelia must also be fully explored. The aim of this study was to determine whether transforming growth factor-alpha and insulin stimulate cell proliferation in rodent vestibular extrasensory epithelia. The cell proliferation marker, tritiated thymidine, was infused along with transforming growth factor-alpha, insulin, or transforming growth factor-alpha plus insulin into the inner ears of adult rats via osmotic pumps. Effects of the test agents were assessed on normal and drug-damaged utricles. Drug damage was produced by delivering gentamicin directly into the inner ear before the infusion of test agent. Animals were killed 4 or 10 days after pump placement. Utricles were sectioned, processed for autoradiography, and examined for labeled cells within the extrasensory epithelia. In normal animals, transforming growth factor-alpha plus insulin stimulated DNA synthesis in all regions of the extrasensory epithelia, suggesting that these agents are mitogenic for these tissues.