Weiskirchen Ralf, Lonardo Amedeo
Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, 52074 Aachen, Germany.
Department of Internal Medicine, Azienda Ospedaliero-Universitaria of Modena (-2023), 41125 Modena, Italy.
Int J Mol Sci. 2025 Jul 2;26(13):6382. doi: 10.3390/ijms26136382.
In women, gonadal hormones play a crucial regulatory role in body fat distribution and glucose-lipidic homeostasis, which are closely associated with the hepatic steatogenesis and intrahepatic inflammatory pathways. Accumulating evidence supports the idea that hepatic health is closely linked to endocrine ovarian function through hormonal, metabolic, and immunological communications, collectively known as the "ovary-liver axis". This review presents the molecular mechanisms involved in sex hormone synthesis, metabolism, and signaling pathways along the ovary-liver axis, focusing on dysregulated mechanisms that may contribute to common disorders and, specifically to hepatic derangements in the context of altered ovarian function. Additionally, we analyzed epidemiological evidence supporting the ovary-liver axis, specifically examining meta-analytic studies exploring the connection between polycystic ovary syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD). We also discuss studies linking hypogonadism with liver health, with a specific focus on Turner syndrome and MASLD. Furthermore, we explore the impact of menopause on liver health. Our integrated molecular and epidemiological approach identifies important clinical and public health implications, aiming to uncover potentially innovative interventions and effective strategies for managing disease progression. However, unexplored areas within the ovary-liver axis highlight the need for further research on causal pathways.
在女性中，性腺激素在身体脂肪分布和糖脂稳态中发挥着关键的调节作用，而这两者与肝脏脂肪生成和肝内炎症途径密切相关。越来越多的证据支持这样一种观点，即肝脏健康通过激素、代谢和免疫通讯与卵巢内分泌功能紧密相连，这些通讯统称为“卵巢-肝脏轴”。本综述介绍了沿卵巢-肝脏轴的性激素合成、代谢和信号通路所涉及的分子机制，重点关注可能导致常见疾病，特别是在卵巢功能改变情况下导致肝脏紊乱的失调机制。此外，我们分析了支持卵巢-肝脏轴的流行病学证据，特别考察了探索多囊卵巢综合征与代谢功能障碍相关脂肪性肝病（MASLD）之间联系的荟萃分析研究。我们还讨论了将性腺功能减退与肝脏健康联系起来的研究，特别关注特纳综合征和MASLD。此外，我们探讨了更年期对肝脏健康的影响。我们综合的分子和流行病学方法确定了重要的临床和公共卫生意义，旨在揭示潜在的创新干预措施和管理疾病进展的有效策略。然而，卵巢-肝脏轴内未探索的领域凸显了对因果途径进行进一步研究的必要性。
