The impact of testosterone on aging-related remodeling of salivary glands

• Autor(a) principal: Santos, João Miguel Valente
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/39618
• topic: Salivary glands; Submandibular gland’s proteome; Testosterone; Aging; Rats; GeLC-MS/MS

Salivary glands play an important role in the secretion of saliva into the oral cavity, influencing salivary composition and oral health. However, the molecular profile of salivary glands is poorly understood, especially in clinical scenarios associated with changes in sex hormone levels. Therefore, our study aimed to investigate how chronic exposure to supraphysiological testosterone levels affects salivary gland remodelling, with a particular focus on proteome adaptation. To achieve this goal, male Wistar rats were implanted subcutaneously at 12 weeks-of-age with devices that release testosterone. At 35 and 61 weeks-of-age, the animals were sacrificed, and their salivary glands were harvested for histological and molecular characterization. The data showed that the submandibular glands were more sensitive to testosterone compared with the parotid glands, as evidenced primarily by a significantly higher ratio of gland mass to body weight. Further analysis of the submandibular glands revealed histologic evidence of acinar cell hypertrophy. At the molecular level, no changes in tissue levels of androgen receptor (AR) and estrogen receptor alpha were detected despite significantly increased levels of circulating sex hormones. GeLC- MS /MS analysis of submandibular gland extracts identified 308 different proteins, 12 of which were modulated by testosterone. Of the common proteins identified from the CTRL and TEST groups, 14 were up-regulated by testosterone, but no relevant interactions were observed between them. In addition, zymographic analysis of the submandibular glands revealed a similar proteolytic profile between the CTRL and TEST groups, with no significant differences observed in optical density values between the two groups. However, our data highlight the contribution of kallikreins (Klk) to the proteolytic activity of these glands, as seen in the zymography gel profile. When looking at the individual proteins that were up-regulated in the TEST group, the stronger expression of Klk3 in the mandibular glands of TEST rats was striking (2-fold increase compared with the CTRL group). Moreover, this protease was also the only kallikrein that showed interaction with the AR, suggesting that Klk3 is a target of this receptor. These results shed light on the differential response of salivary glands to testosterone exposure and provide insight into the proteome-level changes associated with this exposure. Understanding the molecular adaptations in the salivary glands may contribute to a better understanding of oral health and the development of potential therapeutic interventions.