Department of Clinical Medicine and Surgery, University of Naples 'Federico II', Naples, Italy.
Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II.
Eur Thyroid J. 2023 Apr 26;12(3). doi: 10.1530/ETJ-22-0228. Print 2023 Jun 1.
There is increasing evidence that thyroid hormones (THs) work in an integrative fashion with androgen receptors (ARs) to regulate gonadal differentiation and reproductive function. Studies reveal that THs have interactions with the AR promoter region and increase AR expression. THs also have a role in the regulation of enzymes involved in the biosynthesis of androgens, such as 5α-reductase, which is essential in the conversion of testosterone into its active form, 5α-dihydrotestosterone. Additionally, the presence of androgen response elements in the promoter regions of TH-related genes, such as deiodinases and TH receptor isoforms, has been identified in some vertebrates, indicating a mutual interaction between THs and ARs. Since the androgen signaling pathway, mediated by ARs, plays a key role in the formation and progression of prostate cancer (PCa), the existence of crosstalk between THs and ARs supports the epidemiologic and experimental evidence indicating a relationship between the high incidence of PCa and hyperthyroidism. This article aims to review the role of androgen-TH crosstalk in PCa and its implication in clinical management. As life expectancy is growing these days, it can increase the number of patients with PCa and the critical relevance of the disease. In order to gain better knowledge about PCa and to improve clinical management, it is essential to get better insight into the key factors related to the formation and progression of this cancer.
越来越多的证据表明,甲状腺激素(THs)与雄激素受体(ARs)以整合的方式协同作用,调节性腺分化和生殖功能。研究表明,THs 与 AR 启动子区域相互作用,增加 AR 的表达。THs 还在调节参与雄激素生物合成的酶的活性中发挥作用,如 5α-还原酶,它在将睾酮转化为其活性形式 5α-二氢睾酮中起关键作用。此外,一些脊椎动物的 TH 相关基因(如脱碘酶和 TH 受体亚型)的启动子区域中存在雄激素反应元件,表明 THs 和 ARs 之间存在相互作用。由于雄激素信号通路通过 AR 介导,在前列腺癌(PCa)的形成和进展中发挥关键作用,因此 THs 和 ARs 之间存在串扰,支持了高发病率的 PCa 和甲状腺功能亢进之间存在关系的流行病学和实验证据。本文旨在综述雄激素-TH 串扰在 PCa 中的作用及其在临床管理中的意义。由于当今预期寿命的增长,可能会增加患有 PCa 的患者数量,以及该疾病的关键相关性。为了更好地了解 PCa 并改善临床管理,必须更好地了解与这种癌症的形成和进展相关的关键因素。