The Laryngoscope V C 2009 The American Laryngological, Rhinological and Otological Society, Inc. Somatostatin and Gentamicin-Induced Auditory Hair Cell Loss Antje Caelers, PhD; Arianne Monge, MD; Yves Brand, MD; Daniel Bodmer, MD, PhD Objective/Hypothesis: Hair cells of the mammalian auditory system do not regenerate, and therefore their loss leads to irreversible hearing loss. Aminoglycosides, among other substances, can irreversibly damage hair cells. Somatostatin, a pep- tide with hormone/neurotransmitter properties, has neuroprotective effects by binding to its receptor. In this study, we tested whether somatostatin can protect hair cells from gentamicin-induced damage in vitro. Study Design: This study confirmed the expres- sion of somatostatin receptor mRNA within the coch- lea and analyzed the effect of somatostatin on genta- micin-induced hair cell damage and death in vitro. Methods: Expression of somatostatin receptor mRNA in the rat cochlea was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Protection of auditory hair cells from gentamicin was tested using two different concentrations (1 lM and 5 lM, respectively) of somatostatin. Results: We detected somatostatin receptor-1 and -2 mRNA and in the organ of Corti (OC), spiral ganglion, and stria vascularis by RT-PCR. Moreover, we could see significantly less hair cell loss in the OCs that were pretreated with either 1 lM or 5 lM of somatostatin as compared with samples treated with gentamicin alone. Conclusions: Decreased hair cell loss in somato- statin-treated samples that had been exposed to gen- tamicin provides evidence for a protective effect of so- matostatin in aminoglycoside-induced hair cell death in vitro. Key Words: Aminoglycosides, gentamicin, hair cells, somatostatin, somatostatin receptor. Laryngoscope, 119:933–937, 2009 INTRODUCTION Hearing loss due to sensorineural damage has been recognized for over a century. Until recently, damage to cochlear hair cells and neurons has been regarded as an inevitable consequence of age, genetic conditions, or ex- posure to certain environmental stimuli. During the past several years, however, some of the critical intracellular events that mediate aspects of damage to hair cells have been discovered. 1,2 In a large number of studies amino- glycosides have been utilized as inducers of hair cell death, and a significant progress in understanding ami- noglyoside-induced hair cell death has been made. 3,4 After aminoglycoside exposure, cellular and biochemical alterations in the hair cells of the organ of Corti (OC) are set into motion. Reactive oxygen species have been detected in vitro soon after exposure to aminoglyco- sides. 5 In addition, it has been demonstrated that small GTPases, such as Ras and Rho/Rac/Cdc42, as well as the c-Jun-N-terminal kinase (JNK) signalling pathway, are activated in cells exposed to the drug. 6–9 Finally, cas- pases are activated and hair cells undergo apoptotic cell death after prolonged aminoglycoside exposure. 10,11 Similar to the research in the inner ear, a molecular biology approach has advanced the understanding of the molecular mechanisms involved in the damage and death of retina cells. The retina in the eye is the sensory organ for light perception and the cochlea in the inner ear is the organ for sound perception. They share com- mon characteristics. Both the retina and the inner ear arise from neuroepithelium, and both harbor sensitive sensory cells together with supporting cells. Both organs display a complex and highly organized microarchitec- ture. Therefore, it is not surprising that the molecular events involved in damage and death of hair cells share similar features to those in retinal cell damage and death. Studies over the last few years in mice show that the peptide hormone/neurotransmitter somatostatin and its receptors (sst1–sst5) appear to play an important role in retinal cell death. 12,13 Somatostatin is widely distrib- uted throughout the central nervous system and peripheral tissues in mammals. 14 The effects of somato- statin are mediated via its interaction with specific membrane-bound receptors. Five different subtypes of somatostatin receptors (sst1–sst5) have been character- ized, all of them belonging to the superfamily of seven transmembrane spanning G-protein-coupled recep- tors. 14,15 It has been demonstrated that somatostatin and its receptors (sst1–sst5) are expressed in the From the Department of Biomedicine University Hospital Basel and the Klinik fu ¨r Ohren-, Nasen-, Halskrankheiten University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland. Editor’s Note: This Manuscript was accepted for publication August 22, 2008. Send correspondence to Daniel Bodmer, MD, PhD, Klinik fu ¨r Ohren-, Nasen-, Halskrankheiten University Hospital Basel, Petersgra- ben 4, 4031 Basel, Switzerland. E-mail: dbodmer@uhbs.ch DOI: 10.1002/lary.20058 Laryngoscope 119: May 2009 Caelers et al.: Somatostatin and the Inner Ear 933