The cochlea as an independent neuroendocrine organ: Expression and possible roles of a local hypothalamic–pituitary–adrenal axis-equivalent signaling system

Abstract

A key property possessed by the mammalian cochlea is its ability to dynamically alter its own sensitivity. Because hair cells and ganglion cells are prone to damage following exposure to loud sound, extant mechanisms limiting cochlear damage include modulation involving both the mechanical (via outer hair cell motility) and neural signaling (via inner hair cell-ganglion cell synapses) steps of peripheral auditory processing. Feedback systems such as that embodied by the olivocochlear system can alter sensitivity, but respond only after stimulus encoding, allowing potentially damaging sounds to impact the inner ear before sensitivity is adjusted. Less well characterized are potential cellular signaling systems involved in protection against metabolic stress and resultant damage. Although pharmacological manipulation of the olivocochlear system may hold some promise for attenuating cochlear damage, targeting this system may still allow damage to occur that does not depend on a fully functional feedback loop for its mitigation. Thus, understanding endogenous cell signaling systems involved in cochlear protection may lead to new strategies and therapies for prevention of cochlear damage and consequent hearing loss. We have recently discovered a novel cochlear signaling system that is molecularly equivalent to the classic hypothalamic-pituitary-adrenal (HPA) axis. This cochlear HPA-equivalent system functions to balance auditory sensitivity and susceptibility to noise-induced hearing loss, and also protects against cellular metabolic insults resulting from exposures to ototoxic drugs. This system may represent a local cellular response system designed to mitigate damage arising from various types of insult.

Urocortin 3 signalling in the auditory brainstem aids recovery of hearing after reversible noise‐induced threshold shift

“…; Basappa et al . ). In the present study, we demonstrate that intact UCN3 signalling in the auditory pathway contributes to the prevention of age‐ and noise‐induced hearing loss.…”

“…Previous studies suggest that alterations in corticotropin releasing factor signalling results in abnormal auditory function (Graham et al 2010;Basappa et al 2012). In the present study, we demonstrate that intact UCN3 signalling in the auditory pathway contributes to the prevention of age-and noise-induced hearing loss.…”

Melatonin Attenuates Noise Stress-induced Gastrointestinal Motility Disorder and Gastric Stress Ulcer: Role of Gastrointestinal Hormones and Oxidative Stress in Rats

“…In addition, CRF expression has been described in the cochlea, indicating that not only the start point (CRF) but also the end point (glucocorticoid receptors) of the systemic HPA axis signaling are expressed in the cochlea. 29 It is believed that cochlea is an independent neuroendocrine organ. Besides other extra-hypothalamic that impacts within the brain, these hormones increase the activity of the HPA-axis and the release of corticosterone (eg, cortisol) from the adrenal cortex.…”

Genes and Hearing Loss: Relationship to Oxidative Stress and Free Radical Formation

“…Recent expression and genetic mutant studies are consistent with a local neuroendocrine system involving corticotropin-releasing hormone and cognate receptors that may participate in such an intrinsic system (for review, see Basappa et al 2012 ).…”