山东大学耳鼻喉眼学报 ›› 2025, Vol. 39 ›› Issue (6): 46-53.doi: 10.6040/j.issn.1673-3770.0.2024.517
• 论著 • 上一篇
唐茜1,黄茂凌1,张吉强2,钟诚1
TANG Xi1, HUANG Maoling1, ZHANG Jiqiang2, ZHONG Cheng1
摘要: 目的 探讨初级听皮层(primary auditory cortex, A1)中芳香化酶(aromatase, AROM)及三种雌激素受体(estrogen receptors, ERs):雌激素受体α(estrogen receptor alpha, ERα)、雌激素受体β(estrogen receptor beta, ERβ)和G蛋白偶联受体30(G protein-coupled receptor, GPR30)在听觉发育中的表达及作用。 方法 选取出生后7日龄(P7)、14日龄(P14)、21日龄(P21)、30日龄(P30)和60日龄(P60)的C57BL/6J雄性小鼠,采用听觉脑干诱发电位(auditory brainstem response, ABR)检测听阈;采用qRT-PCR、Western bloting、免疫组化等检测小鼠A1内AROM和ERs表达变化;进行表达量与听阈的Spearman相关性分析。 结果 ABR从P14可检测后持续下降(P<0.05),于P30达到成熟水平。qPCR显示AROM、GPR30和ERβ表达随日龄递增(P<0.05);ERα在P30时达到峰值(P<0.05)。蛋白水平(Western bloting和免疫组化)实验的结果表明AROM和ERs的表达量随发育显著升高(P<0.05)。Spearman相关性分析结果表明,AROM、ERβ的表达与听力阈值的发育变化为强相关(∣rs∣分别为0.75、0.72),GPR30呈弱相关(∣rs∣为0.64),ERα无显著相关性。 结论 小鼠出生后听力逐渐发育完善,A1内AROM及GPR30、ERβ表达水平逐渐升高,提示AROM-GPR30/ERβ信号轴可能促进了小鼠听觉功能的建立和成熟。
中图分类号:
| [1] 杨旻, 朱晓燕, 王旭. 感音神经性聋的代谢组学研究进展[J]. 山东大学耳鼻喉眼学报, 2024, 38(2): 113-121. doi:10.6040/j.issn.1673-3770.0.2023.263 YANG Min, ZHU Xiaoyan, WANG Xu. Progress in metabolomics research in sensorineural hearing loss[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(2): 113-121. doi:10.6040/j.issn.1673-3770.0.2023.263 [2] Pearson JD, Morrell CH, Gordon-Salant S, et al. Gender differences in a longitudinal study of age-associated hearing loss[J]. J Acoust Soc Am, 1995, 97(2): 1196-1205. [3] Pottoo FH, Bhowmik M, Vohora D. Raloxifene protects against seizures and neurodegeneration in a mouse model mimicking epilepsy in postmenopausal woman[J]. Eur J Pharm Sci, 2014, 65: 167-173. doi: 10.1016/j.ejps.2014.09.002 [4] Hederstierna C, Hultcrantz M, Collins A, et al. Hearing in women at menopause. Prevalence of hearing loss, audiometric configuration and relation to hormone replacement therapy[J]. Acta Otolaryngol, 2007, 127(2): 149-155. doi: 10.1080/00016480600794446 [5] Predná L, Habánová M, Sláviková E, et al. Hormonal contraceptives and hormone replacement therapy as a possible factor of breast cancer[J]. Rocz Panstw Zakl Hig, 2015, 66(3): 269-274. [6] Naftolin F, Ryan KJ, Davies IJ, et al. The formation of estrogens by central neuroendocrine tissues[J]. Recent Prog Horm Res, 1975, 31: 295-319. doi: 10.1016/b978-0-12-571131-9.50012-8 [7] Santen RJ, Brodie H, Simpson ER, et al. History of aromatase: Saga of an important biological mediator and therapeutic target[J]. Endocr Rev, 2009, 30(4): 343-375. [8] McCullough LD, Blizzard K, Simpson ER, et al. Aromatase cytochrome P450 and extragonadal estrogen play a role in ischemic neuroprotection[J]. J Neurosci, 2003, 23(25): 8701-8705. [9] Nilsen J, Mor G, Naftolin F. Estrogen-regulated developmental neuronal apoptosis is determined by estrogen receptor subtype and the Fas/Fas ligand system[J]. J Neurobiol, 2000, 43(1): 64-78. [10] Gruber CJ, Tschugguel W, Schneeberger C, et al. Production and actions of estrogens[J]. N Engl J Med, 2002, 346(5): 340-352. [11] Meltser I, Tahera Y, Simpson E, et al. Estrogen receptor beta protects against acoustic trauma in mice[J]. J Clin Invest, 2008, 118(4): 1563-1570. [12] Milon B, Mitra S, Song Y, et al. The impact of biological sex on the response to noise and otoprotective therapies against acoustic injury in mice[J]. Biol Sex Differ, 2018, 9(1): 12. doi: 10.1186/s13293-018-0171-0 [13] Shuster B, Casserly R, Lipford E, et al. Estradiol protects against noise-induced hearing loss and modulates auditory physiology in female mice[J]. Int J Mol Sci, 2021, 22(22): 12208. doi: 10.3390/ijms222212208 [14] Webster DB. A critical period during postnatal auditory development of mice[J]. Int J Pediatr Otorhinolaryngol, 1983, 6(2): 107-118. [15] Abe T, Kakehata S, Kitani R, et al. Developmental expression of the outer hair cell motor prestin in the mouse[J]. J Membr Biol, 2007, 215(1): 49-56. [16] Bilger RC, Matthies ML, Hammel DR, et al. Genetic implications of gender differences in the prevalence of spontaneous otoacoustic emissions[J]. J Speech Hear Res, 1990, 33(3): 418-432. [17] Jerger J, Hall J. Effects of age and sex on auditory brainstem response[J]. Arch Otolaryngol, 1980, 106(7): 387-391. [18] Alves C, Oliveira CS. Hearing loss among patients with Turner’s syndrome: literature review[J]. Braz J Otorhinolaryngol, 2014, 80(3): 257-263. [19] Curhan SG, Eliassen AH, Eavey RD, et al. Menopause and postmenopausal hormone therapy and risk of hearing loss[J]. Menopause, 2017, 24(9): 1049-1056. [20] Cornil CA, Charlier TD. Rapid behavioural effects of oestrogens and fast regulation of their local synthesis by brain aromatase[J]. J Neuroendocrinol, 2010, 22(7): 664-673. [21] Azcoitia I, Yague JG, Garcia-Segura LM. Estradiol synthesis within the human brain[J]. Neuroscience, 2011, 191: 139-147. doi: 10.1016/j.neuroscience.2011.02.012 [22] Balthazart J, Ball GF. Is brain estradiol a hormone or a neurotransmitter?[J]. Trends Neurosci, 2006, 29(5): 241-249. [23] Stocco C. Tissue physiology and pathology of aromatase[J]. Steroids, 2012, 77(1/2): 27-35. [24] Naftolin F, Ryan KJ, Petro Z. Aromatization of androstenedione by the diencephalon[J]. J Clin Endocrinol Metab, 1971, 33(2): 368-370. [25] Colciago A, Celotti F, Pravettoni A, et al. Dimorphic expression of testosterone metabolizing enzymes in the hypothalamic area of developing rats[J]. Brain Res Dev Brain Res, 2005, 155(2): 107-116. [26] Vierk R, Brandt N, Rune GM. Hippocampal estradiol synthesis and its significance for hippocampal synaptic stability in male and female animals[J]. Neuroscience, 2014, 274: 24-32. doi: 10.1016/j.neuroscience.2014.05.003 [27] Negri-Cesi P, Poletti A, Celotti F. Metabolism of steroids in the brain: a new insight into the role of 5alpha-reductase and aromatase in brain differentiation and functions[J]. J Steroid Biochem Mol Biol, 1996, 58(5/6): 455-466. [28] Soutar CN, Grenier P, Patel A, et al. Brain-generated 17β-estradiol modulates long-term synaptic plasticity in the primary auditory cortex of adult male rats[J]. Cereb Cortex, 2022, 32(10): 2140-2155. [29] Yokosuka M, Okamura H, Hayashi S. Transient expression of estrogen receptor-immunoreactivity(ER-IR)in the layer V of the developing rat cerebral cortex[J]. Brain Res Dev Brain Res, 1995, 84(1): 99-108. [30] Sharma PK, Thakur MK. Expression of estrogen receptor(ER)alpha and beta in mouse cerebral cortex: effect of age, sex and gonadal steroids[J]. Neurobiol Aging, 2006, 27(6): 880-887. [31] Charitidi K, Canlon B. Estrogen receptors in the central auditory system of male and female mice[J]. Neuroscience, 2010, 165(3): 923-933. [32] Montelli S, Peruffo A, Zambenedetti P, et al. Expression of aromatase P450(AROM)in the human fetal and early postnatal cerebral cortex[J]. Brain Res, 2012, 1475: 11-18. doi: 10.1016/j.brainres.2012.08.010 [33] Matsuda K, Sakamoto H, Mori H, et al. Expression and intracellular distribution of the G protein-coupled receptor 30 in rat hippocampal formation[J]. Neurosci Lett, 2008, 441(1): 94-99. [34] Krentzel AA, Macedo-Lima M, Ikeda MZ, et al. A membrane G-protein-coupled estrogen receptor is necessary but not sufficient for sex differences in Zebra finch auditory coding[J]. Endocrinology, 2018, 159(3): 1360-1376. [35] Fan XT, Xu HW, Warner M, et al. ERbeta in CNS: new roles in development and function[J]. Prog Brain Res, 2010, 181: 233-250. doi: 10.1016/S0079-6123(08)81013-8 [36] Spencer-Segal JL, Tsuda MC, Mattei L, et al. Estradiol acts via estrogen receptors alpha and beta on pathways important for synaptic plasticity in the mouse hippocampal formation[J]. Neuroscience, 2012, 202: 131-146. doi: 10.1016/j.neuroscience.2011.11.035 [37] Tremere LA, Burrows K, Jeong JK, et al. Organization of estrogen-associated circuits in the mouse primary auditory cortex[J]. J Exp Neurosci, 2011, 2011(5): 45-60. [38] Wilson ME, Westberry JM. Regulation of oestrogen receptor gene expression: new insights and novel mechanisms[J]. J Neuroendocrinol, 2009, 21(4): 238-242. |
| [1] | 汪晓锋 ,程金妹,林 昶 . 雌激素与老年性耳聋的关系[J]. 山东大学耳鼻喉眼学报, 2007, 21(5): 427-429 . |
|
||