School of Pharmacy, Fudan University, Shanghai 200032, China.
Laboratory of Reproductive Pharmacology, NHC Key Laboratory of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai 200032, China.
Int J Mol Sci. 2022 Feb 28;23(5):2708. doi: 10.3390/ijms23052708.
Accumulating evidence has shown that thyroid hormones (THs) are vital for female reproductive system homeostasis. THs regulate the reproductive functions through thyroid hormone receptors (THRs)-mediated genomic- and integrin-receptor-associated nongenomic mechanisms, depending on TH ligand status and DNA level, as well as transcription and extra-nuclear signaling transduction activities. These processes involve the binding of THs to intracellular THRs and steroid hormone receptors or membrane receptors and the recruitment of hormone-response elements. In addition, THs and other reproductive hormones can activate common signaling pathways due to their structural similarity and shared DNA consensus sequences among thyroid, peptide, and protein hormones and their receptors, thus constituting a complex and reciprocal interaction network. Moreover, THs not only indirectly affect the synthesis, secretion, and action of reproductive hormones, but are also regulated by these hormones at the same time. This crosstalk may be one of the pivotal factors regulating female reproductive behavior and hormone-related diseases, including tumors. Elucidating the interaction mechanism among the aforementioned hormones will contribute to apprehending the etiology of female reproductive diseases, shedding new light on the treatment of gynecological disorders.
越来越多的证据表明,甲状腺激素(THs)对女性生殖系统稳态至关重要。THs 通过甲状腺激素受体(THRs)介导的基因组和整合素受体相关的非基因组机制来调节生殖功能,这取决于 TH 配体状态和 DNA 水平,以及转录和核外信号转导活性。这些过程涉及 THs 与细胞内 THRs 和甾体激素受体或膜受体的结合,以及激素反应元件的募集。此外,由于甲状腺、肽和蛋白质激素及其受体之间存在结构相似性和共同的 DNA 共识序列,THs 和其他生殖激素可以激活共同的信号通路,从而构成一个复杂的相互作用网络。此外,THs 不仅间接影响生殖激素的合成、分泌和作用,同时也受到这些激素的调节。这种串扰可能是调节女性生殖行为和与激素相关疾病(包括肿瘤)的关键因素之一。阐明上述激素之间的相互作用机制将有助于了解女性生殖疾病的病因,并为妇科疾病的治疗提供新的思路。