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Prolactin expression in the cochlea of aged BALB/c mice is gender biased and correlates to loss of bone mineral density and hearing loss.

Marano RJ, Tickner J, Redmond SL - PLoS ONE (2013)

Bottom Line: We found that prolactin expression was exclusive to the female mice.However, no gender differences in expression of osteoprotegerin or receptor activator of nuclear factor-kappaB ligand could be found.These results provide a possible mechanism for an age related hearing loss sub-type that is associated with gender and provides clues as to how this gender bias in hearing loss develops.

View Article: PubMed Central - PubMed

Affiliation: Ear Science Institute Australia, Subiaco, Western Australia, Australia. rob.marano@earscience.org.au

ABSTRACT
Prolactin is a versatile hormone with over 300 known functions and predominantly expressed in the pituitary. However, its expression has additionally been found in a number of extrapituitary organs. Recently, we described the expression of prolactin in the inner ear of mice, where it was correlated to age. Previous research has shown prolactin to be linked to abnormal bone metabolism and hearing loss due to changes in morphology of the bony otic capsule. Here we further investigated the relationship between prolactin, hearing loss and cochlea bone metabolism. BALB/c mice were tested for hearing using ABR at 6 and 12 months of age. Bone mineral density of the cochlea was evaluated using microCT scanning. Prolactin expression was calculated using quantitative real time PCR. Expression of the key regulators of bone metabolism, osteoprotegerin and receptor activator of nuclear factor-kappaB ligand were also determined. We found that prolactin expression was exclusive to the female mice. This also correlated to a greater threshold shift in hearing for the females between 6 and 12 months of age. Analyses of the cochlea also show that the bone mineral density was lower in females compared to males. However, no gender differences in expression of osteoprotegerin or receptor activator of nuclear factor-kappaB ligand could be found. Further analysis of cochlea histological sections revealed larger ostocyte lacunae in the females. These results provide a possible mechanism for an age related hearing loss sub-type that is associated with gender and provides clues as to how this gender bias in hearing loss develops. In addition, it has the potential to lead to treatment for this specific type of hearing loss.

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Threshold shift in hearing ability for male and female mice.The change in hearing acuity between 6 and 12 months for female and male mice were calculated for a click response and at various pure tone frequencies. It was found that females displayed a significantly greater shift in hearing threshold compared to males at 4 KHz (p = 0.005) and 8 KHz (p = 0.007). Error bars denote the SEM and * indicates a significance of p<0.05.
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pone-0063952-g003: Threshold shift in hearing ability for male and female mice.The change in hearing acuity between 6 and 12 months for female and male mice were calculated for a click response and at various pure tone frequencies. It was found that females displayed a significantly greater shift in hearing threshold compared to males at 4 KHz (p = 0.005) and 8 KHz (p = 0.007). Error bars denote the SEM and * indicates a significance of p<0.05.

Mentions: Mean ABR thresholds were calculated for male and female mice at 6 months and 12 months of age for a click response and at pure tones. At 6 months of age, both sexes displayed a typical ABR threshold curve (Figure 2A) for this strain of mouse, characterized by substantial hearing loss at the higher frequency of 32 KHz [18]. Additionally, although the shape of the curve was similar, males possessed significantly higher ABR thresholds than females for pure tone stimuli at 8, 16 and 32 KHz (Table 1) when analyzed using the Wilcoxon Rank Sum/Mann-Whitney U-Test. However, at 12 months of age, the situation appeared to reverse with the males recording statistically similar thresholds compared to the females for all corresponding stimuli (Figure 2B). Both sexes essentially recorded complete hearing loss at 32 KHz with thresholds above 95 dB (Table 1). Further analysis calculating the ABR threshold shift between 6 and 12 months revealed significant differences in loss of hearing between females and males (Figure 3) when analyzed using Repeated Measures ANOVA. For a click stimulus it appeared that females suffered a greater threshold shift of 10 dB ±1.29 compared to males, which demonstrated an ABR threshold shift of 3.75 dB ±2.39. However, this was not considered significant (F = 5.12; p = 0.058). For a pure tone stimulus at 4 KHz, females recorded a significantly (F = 15.89; p = 0.005) greater increase of ABR threshold of 16.66 dB ±2.79 compared to males, which recorded a reduction of 1.25 dB ±3.75. This result is also reflected in the calculations at 8 KHz, which shows females recording a mean threshold increase of 5.83 dB ±2.39, while the males recorded a threshold reduction of 3.75 dB ±1.25 (F = 14.44; p = 0.007). No significant difference was detected between females and males at 16 KHz and 32 KHz (F = 0.881; p = 0.380 and F = 1.89; p = 0.212 respectively).


Prolactin expression in the cochlea of aged BALB/c mice is gender biased and correlates to loss of bone mineral density and hearing loss.

Marano RJ, Tickner J, Redmond SL - PLoS ONE (2013)

Threshold shift in hearing ability for male and female mice.The change in hearing acuity between 6 and 12 months for female and male mice were calculated for a click response and at various pure tone frequencies. It was found that females displayed a significantly greater shift in hearing threshold compared to males at 4 KHz (p = 0.005) and 8 KHz (p = 0.007). Error bars denote the SEM and * indicates a significance of p<0.05.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3646833&req=5

pone-0063952-g003: Threshold shift in hearing ability for male and female mice.The change in hearing acuity between 6 and 12 months for female and male mice were calculated for a click response and at various pure tone frequencies. It was found that females displayed a significantly greater shift in hearing threshold compared to males at 4 KHz (p = 0.005) and 8 KHz (p = 0.007). Error bars denote the SEM and * indicates a significance of p<0.05.
Mentions: Mean ABR thresholds were calculated for male and female mice at 6 months and 12 months of age for a click response and at pure tones. At 6 months of age, both sexes displayed a typical ABR threshold curve (Figure 2A) for this strain of mouse, characterized by substantial hearing loss at the higher frequency of 32 KHz [18]. Additionally, although the shape of the curve was similar, males possessed significantly higher ABR thresholds than females for pure tone stimuli at 8, 16 and 32 KHz (Table 1) when analyzed using the Wilcoxon Rank Sum/Mann-Whitney U-Test. However, at 12 months of age, the situation appeared to reverse with the males recording statistically similar thresholds compared to the females for all corresponding stimuli (Figure 2B). Both sexes essentially recorded complete hearing loss at 32 KHz with thresholds above 95 dB (Table 1). Further analysis calculating the ABR threshold shift between 6 and 12 months revealed significant differences in loss of hearing between females and males (Figure 3) when analyzed using Repeated Measures ANOVA. For a click stimulus it appeared that females suffered a greater threshold shift of 10 dB ±1.29 compared to males, which demonstrated an ABR threshold shift of 3.75 dB ±2.39. However, this was not considered significant (F = 5.12; p = 0.058). For a pure tone stimulus at 4 KHz, females recorded a significantly (F = 15.89; p = 0.005) greater increase of ABR threshold of 16.66 dB ±2.79 compared to males, which recorded a reduction of 1.25 dB ±3.75. This result is also reflected in the calculations at 8 KHz, which shows females recording a mean threshold increase of 5.83 dB ±2.39, while the males recorded a threshold reduction of 3.75 dB ±1.25 (F = 14.44; p = 0.007). No significant difference was detected between females and males at 16 KHz and 32 KHz (F = 0.881; p = 0.380 and F = 1.89; p = 0.212 respectively).

Bottom Line: We found that prolactin expression was exclusive to the female mice.However, no gender differences in expression of osteoprotegerin or receptor activator of nuclear factor-kappaB ligand could be found.These results provide a possible mechanism for an age related hearing loss sub-type that is associated with gender and provides clues as to how this gender bias in hearing loss develops.

View Article: PubMed Central - PubMed

Affiliation: Ear Science Institute Australia, Subiaco, Western Australia, Australia. rob.marano@earscience.org.au

ABSTRACT
Prolactin is a versatile hormone with over 300 known functions and predominantly expressed in the pituitary. However, its expression has additionally been found in a number of extrapituitary organs. Recently, we described the expression of prolactin in the inner ear of mice, where it was correlated to age. Previous research has shown prolactin to be linked to abnormal bone metabolism and hearing loss due to changes in morphology of the bony otic capsule. Here we further investigated the relationship between prolactin, hearing loss and cochlea bone metabolism. BALB/c mice were tested for hearing using ABR at 6 and 12 months of age. Bone mineral density of the cochlea was evaluated using microCT scanning. Prolactin expression was calculated using quantitative real time PCR. Expression of the key regulators of bone metabolism, osteoprotegerin and receptor activator of nuclear factor-kappaB ligand were also determined. We found that prolactin expression was exclusive to the female mice. This also correlated to a greater threshold shift in hearing for the females between 6 and 12 months of age. Analyses of the cochlea also show that the bone mineral density was lower in females compared to males. However, no gender differences in expression of osteoprotegerin or receptor activator of nuclear factor-kappaB ligand could be found. Further analysis of cochlea histological sections revealed larger ostocyte lacunae in the females. These results provide a possible mechanism for an age related hearing loss sub-type that is associated with gender and provides clues as to how this gender bias in hearing loss develops. In addition, it has the potential to lead to treatment for this specific type of hearing loss.

Show MeSH
Related in: MedlinePlus