LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
Department of Medical Sciences, Institute of Biomedicine-iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal.
Int J Mol Sci. 2023 Dec 31;25(1):550. doi: 10.3390/ijms25010550.
The salivary glands play a central role in the secretion of saliva, whose composition and volume affect oral and overall health. A lesser-explored dimension encompasses the possible changes in salivary gland proteomes in response to fluctuations in sex hormone levels. This study aimed to examine the effects of chronic exposure to testosterone on salivary gland remodeling, particularly focusing on proteomic adaptations. Therefore, male Wistar rats were implanted with subcutaneous testosterone-releasing devices at 14 weeks of age. Their submandibular glands were histologically and molecularly analyzed 47 weeks later. The results underscored a significant increase in gland mass after testosterone exposure, further supported by histologic evidence of granular duct enlargement. Despite increased circulating sex hormones, there was no detectable shift in the tissue levels of estrogen alpha and androgen receptors. GeLC-MS/MS and subsequent bioinformatics identified 308 proteins in the submandibular glands, 12 of which were modulated by testosterone. Of note was the pronounced upregulation of Klk3 and the downregulation of Klk6 and Klk7 after testosterone exposure. Protein-protein interaction analysis with the androgen receptor suggests that Klk3 is a potential target of androgenic signaling, paralleling previous findings in the prostate. This exploratory analysis sheds light on the response of salivary glands to testosterone exposure, providing proteome-level insights into the associated weight and histological changes.
唾液腺在唾液分泌中起着核心作用,唾液的成分和体积影响口腔和整体健康。一个较少被探索的方面包括唾液腺蛋白质组可能会对性激素水平波动做出反应而发生变化。本研究旨在检查慢性暴露于睾丸激素对唾液腺重塑的影响,特别是关注蛋白质组学的适应。因此,雄性 Wistar 大鼠在 14 周龄时植入皮下释放睾丸激素的装置。47 周后,对其颌下腺进行组织学和分子分析。结果表明,睾丸激素暴露后腺体质量显著增加,组织学证据进一步支持了颗粒管扩张的证据。尽管循环性激素增加,但组织水平的雌激素 alpha 和雄激素受体没有检测到变化。GeLC-MS/MS 和随后的生物信息学在颌下腺中鉴定出 308 种蛋白质,其中 12 种受睾丸激素调节。值得注意的是,睾丸激素暴露后 Klk3 的表达明显上调,而 Klk6 和 Klk7 的表达下调。与雄激素受体的蛋白质-蛋白质相互作用分析表明,Klk3 是雄激素信号的潜在靶点,与前列腺中的先前发现相平行。这项探索性分析揭示了唾液腺对睾丸激素暴露的反应,提供了蛋白质组水平对相关体重和组织学变化的见解。