Research paper
Glucocorticoid receptors modulate auditory sensitivity to acoustic trauma

https://doi.org/10.1016/j.heares.2006.05.009Get rights and content

Abstract

Glucocorticoids are widely used to treat different hearing disorders yet the exact mechanisms of glucocorticoid action on the inner ear are not known. The inner ear of both humans and experimental animals demonstrate an abundance of glucocorticoid receptors (GRs) in both neuronal and non-neuronal tissues. In this review, we discuss how activation of the hypothalamic–pituitary–adrenal axis can directly modulate hearing sensitivity. Recent findings indicate that several factors define the responsiveness of the peripheral auditory system to glucocorticoids including the concentration of agonist, availability of the GR, and the activation of GR and NF-κB. These findings will further our understanding of individual glucocorticoid responsiveness to steroid treatment, and will help improve the development of pharmaceuticals to selectively target GR in the inner ear for individuals with increased sensitivity to acoustic trauma.

Section snippets

Glucocorticoid history

The Nobel Prize in Medicine or Physiology was awarded in 1950 to Philip Hench, Edward Kendall and Tadeus Richtenstein for their work on the identification, characterization, and therapeutic use of hormones of the adrenal cortex, their structure and biological effects. They also studied the biological influence of the synthetic glucocorticoids, prednisone and dexamethasone. Since then, chronic glucocorticoid treatment has been found to be accompanied by serious side-effects, a finding that

Glucocorticoid receptors

Glucocorticoids are small lipophilic compound that are synthesized from cholesterol in the adrenal cortex by cytochrome P450-catalyzed reactions (Aron et al., 2004). Glucocorticoids affect organ development, tissue maturation, wound healing, and they are highly important in the modulation of inflammatory and immune responses (Smoak and Cidlowski, 2004). Glucocorticoids have an effect in almost all organs in the body and sensitivity to them depends on several factors including the availability

Glucocorticoid receptors in the inner ear

GR are expressed almost in all tissues but its concentration varies. GR have been detected in various parts of inner ear in humans and experimental animals (Rarey and Curtis, 1996, Shimazaki et al., 2002, Tahera et al., 2006, ten Cate et al., 1992). In the inner ear GR are localized to both neuronal and non-neuronal tissues and are modulated by acoustic trauma (Rarey et al., 1995, Terunuma et al., 2001, Tahera et al., 2006) or restraint stress (Curtis and Rarey, 1995). The glucocorticoid

Conclusions

The cellular levels of steroid hormone receptors fluctuate in response to stress depending on the individuals’ physiological and endocrine status. Responses of the HPA axis to acoustic stress are regulated by the cellular sensitivity to steroids, which is under control of the receptor availability and expression. It is known that long-term activation of glucocorticoid receptors can be detrimental to the central nervous system, while short-term activation can be advantageous. This review has

Acknowledgements

Supported by grants from the Swedish Research Council, AMF Trygghetsförsäkring, Tysta Skolan, Royal National Institute for Deaf People, and the Karolinska Institute.

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