You Qiang, Song Hequn, Zhu Ziming, Wang Jinzheng, Wang Ruixin, Du Mingjia, Fu Yingjie, Yuan Jinxiang, Tan Rubin
Department of Physiology, Basic Medical School, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, China.
Cell Mol Biol Lett. 2024 Dec 18;29(1):155. doi: 10.1186/s11658-024-00671-w.
Pulmonary hypertension (PH) presents a puzzling sex bias, being more prevalent in women yet often less severe than in men, and the underlying reasons remain unclear. Studies using animal models, and limited clinical data have revealed a protective influence of exogenous estrogens, known as the estrogen paradox. Research suggests that beyond its receptor-mediated effects, estrogen acts through metabolites such as 2-ME2, 4-OHE2, and 16-OHE2, which are capable of exhibiting protective or detrimental effects in PH, prompting the need to explore their roles in PH to untangle sex differences and the estrogen paradox. Hypoxia disrupts the balance of estrogen metabolites by affecting the enzymes responsible for estrogen metabolism. Delving into the role of these metabolic enzymes not only illuminates the sex difference in PH but also provides a potential rationale for the estrogen paradox. This review delves into the intricate interplay between estrogen metabolites, metabolic enzymes, and PH, offering a deeper understanding of sex-specific differences and the perplexing estrogen paradox in the context of this condition.
肺动脉高压（PH）存在一种令人费解的性别偏见，在女性中更为普遍，但通常比男性病情较轻，其根本原因尚不清楚。使用动物模型的研究以及有限的临床数据揭示了外源性雌激素的保护作用，即所谓的雌激素悖论。研究表明，除了其受体介导的作用外，雌激素还通过2-ME2、4-OHE2和16-OHE2等代谢产物发挥作用，这些代谢产物在PH中可能表现出保护或有害作用，这促使人们需要探索它们在PH中的作用，以理清性别差异和雌激素悖论。缺氧通过影响负责雌激素代谢的酶来破坏雌激素代谢产物的平衡。深入研究这些代谢酶的作用不仅可以阐明PH中的性别差异，还为雌激素悖论提供了潜在的理论依据。本综述深入探讨了雌激素代谢产物、代谢酶和PH之间的复杂相互作用，以便在这种情况下更深入地理解性别特异性差异和令人困惑的雌激素悖论。
