Estradiol Treatment and Hormonal Fluctuations During the Estrous Cycle Modulate the Expression of Estrogen Receptors in the Auditory System and the Prepulse Inhibition of Acoustic Startle Response

Abstract

Estrogens' effects on hearing are documented across species, but the responsible molecular mechanisms remain unknown. The presence of estrogen receptors (ER) throughout the auditory system offers a potential pathway of direct estrogenic effects on auditory function, but little is known about how each ER's expression is regulated by the overall hormonal status of the body. In the present study, we determined the effects of ovariectomy and chronic 17β-estradiol treatment on mRNA and protein expression of ERα and ERβ in peripheral (cochlea) and central (inferior colliculus) auditory structures of mice, as well as on auditory-related behavior using the acoustic startle response (ASR), prepulse inhibition (PPI), and habituation of the startle response. 17β-Estradiol treatment down-regulated ERα but not ERβ and increased PPI and latency of the ASR. Neither the magnitude nor the habituation of ASR was affected. Furthermore, ER's mRNA and protein expression in the inner ear were analyzed throughout the estrous cycle (proestrus, estrus, metestrus, and diestrus), revealing a negative correlation of circulating estrogens with ERα expression, whereas ERβ was stable. Our findings show that ER not only are present in both the peripheral and central auditory system but also that circulating estrogen levels down-regulate ERα expression in the auditory system and affect PPI and the latency of ASR, suggesting a key role of ERα as a hormone-induced modulator of the auditory system and behavior.