Experimental estrogen-induced hyperprolactinemia results in bone-related hearing loss in the guinea pig

Abstract

Our group (Horner KC, Guieu R, Magnan J, Chays A, Cazals Y. Neuropsychopharmacology 26: 135–138, 2002) has earlier described hyperprolactinemia in some patients presenting inner ear dysfunction. However, in that study, it was not possible to determine whether hyperprolactinemia was a cause or an effect of the symptoms. To investigate the effect of hyperprolactinemia on inner ear function, we first developed a model of hyperprolactinemia in estrogen-primed Fischer 344 rats and then performed functional studies on pigmented guinea pigs. Hyperprolactinemia induced, after 2 mo, a hearing loss of ∼30–40 dB across all frequencies, as indicated by the compound action potential audiogram. During the 3rd mo, the hearing loss continued to deteriorate. The threshold shifts were more substantial in males than in females. Observations under a dissection microscope revealed bone dysmorphology of the bulla and the cochlea. Light microscopy observations of cryostat sections confirmed bone-related pathology of the bony cochlear bulla and the cochlear wall and revealed morphopathology of the stria vascularis and spiral ligament. Scanning electron microscopy revealed loss of hair cells and stereocilia damage, in particular in the upper three cochlear turns and the two outermost hair cell rows. The data provide the first evidence of otic capsule and hair cell pathology associated with estrogen-induced prolonged hyperprolactinemia and suggest that conditions such as pregnancy, anti-psychotic drug treatment, aging, and/or stress might lead to similar ear dysfunctions.

Receptors for leptin in the otic labyrinth and the cochlear–vestibular nerve of guinea pig are modified in hormone-induced anorexia

“…In agreement with that, reduction in weight gain was observed in estrogen-treated guinea pigs (Horner et al, 2007) and estrogen-treated rats . The estrogen-treated guinea pigs also developed hearing loss with bone dysmorphology of the otic capsule (Horner et al, 2007). The data are in keeping with earlier report of chronic hyperprolactinemia, induced by pituitary grafting for as long as one year, associated with persistent hypolipidemia in mice (Matsuda et al, 1996).…”

“…Estrogen is known to have anorexigenic effects (Versini et al, 2010;Young, 2010). In agreement with that, reduction in weight gain was observed in estrogen-treated guinea pigs (Horner et al, 2007) and estrogen-treated rats . The estrogen-treated guinea pigs also developed hearing loss with bone dysmorphology of the otic capsule (Horner et al, 2007).…”

“…In order to understand better the effect of hyperprolactinemia on the ear we investigated long-term effects of estrogen-induced hyperprolactinemia (Horner et al, 2007). Estrogen is known to have anorexigenic effects (Versini et al, 2010;Young, 2010).…”

“…Furthermore, prolactin receptoredeficient mice, which have hyperprolactinemia, have reduced fat mass (Freemark et al, 2001) as well as modified bone mineralization (Clement-Lacroix et al, 1999). The combined modification of energetic status, including weight loss and anorexia Horner et al, 2007), together Abbreviations: ObR, leptin receptor; GFAP, glial fibrillary acid protein; PLP, proteolipid protein; OPG, osteoprotegerin; RANK, receptor activator of NF-kB; RANKL, receptor activator of NF-kB ligand; NF-kB, nuclear factor kappa-B; BDNF, brain-derived neurotrophic factor; EAE, experimental autoimmune encephalomyelitis.…”

“…with otic labyrinth bone dysmorphology (Horner et al, 2007) led us to hypothesize that leptin could be implicated. Of course, both estrogen and prolactin would also be major actors and their possible roles have been discussed earlier (Horner, 2009;Horner et al, 2007).…”