《生命科学》 2026, 38(9): 1549-1562

泌乳素-泌乳素受体信号在妇科及女性高发疾病中的情境依赖性作用及转化前景

徐 帅¹ , 肖瑞平^1,2,3,*

¹北京大学未来技术学院分子医学研究所，北京 100871 ²北京大学国家膜重点实验室，北京 100871 ³北京大学北大-清华联合生命中心，北京 100871

摘　要：

女性在月经周期、妊娠、哺乳及绝经等不同生理阶段经历显著的内分泌变化，这不仅关系到正常生殖功能的维持，也影响多种女性特异性或高发疾病的发生发展。近年来，人们逐渐认识到泌乳素（prolactin，PRL）是一种具有广泛生物学效应的调节因子。除参与泌乳和生殖调控外，PRL还可影响免疫稳态、能量代谢、组织重塑及痛觉感受等过程，其作用主要由泌乳素受体（prolactin receptor，PRLR）介导。由于PRL具有多种分子形式，可来源于垂体及多种外周组织，且PRLR的亚型构成和下游信号通路存在差异，因此该信号系统的生物学效应在不同组织和疾病背景中呈现出明显的情境依赖性。现有证据提示，PRL-PRLR信号异常并非仅表现为血清PRL升高，还可体现为局部信号增强和特定响应细胞群持续活化。本文从局部炎症维持、组织重塑、神经敏化、免疫耐受失衡及代谢调节等多重病理环节出发，讨论PRL-PRLR轴在子宫内膜异位症、子宫腺肌症、多囊卵巢综合征、女性易感性疼痛及系统性红斑狼疮中的疾病特异性作用及转化意义，为理解PRL-PRLR轴参与妇科及女性高发疾病的病理机制提供了新的视角。

通讯作者：肖瑞平 , Email:xiaor@pku.edu.cn

Context-dependent roles and translational prospects of prolactin-prolactin receptor signaling in gynaecological and female-prevalent diseases

XU Shuai¹ , XIAO Rui-Ping^1,2,3,*

¹Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China ²State Key Laboratory of Membrane Biology, Peking University, Beijing 100871, China ³Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China

Abstract:

Women undergo substantial endocrine changes during the menstrual cycle, pregnancy, lactation and menopause. These physiological changes are essential for reproductive function, but they also influence the onset and progression of a range of female-specific and female-prevalent diseases. Prolactin (PRL), classically defined as a pituitary hormone involved in lactation and reproductive regulation, also exerts broad biological effects on immune homeostasis, energy metabolism, tissue remodeling and nociceptive signaling, mainly through the prolactin receptor (PRLR). The actions of PRL-PRLR signaling are highly context dependent. PRL exists in multiple molecular forms and can be produced not only by the anterior pituitary but also by peripheral tissues and cell types, including the endometrium, decidua, immune cells and adipose tissue. Moreover, tissue-specific PRLR isoforms and downstream signaling programmes differ across cell populations, physiological states and disease contexts. As a result, PRL-PRLR dysregulation is not necessarily reflected by elevated circulating PRL levels. Its pathological relevance may also involve local signal amplification, altered PRLR expression or isoform composition, and sustained activation of specific PRL-responsive cell populations. In this review, we discuss the diseasespecific roles and translational implications of the PRL-PRLR axis in endometriosis, adenomyosis, polycystic ovary syndrome, female-prevalent pain disorders and systemic lupus erythematosus. We focus on pathological processes that recur across these conditions, including persistent local inflammation, tissue  emodeling, neural sensitization, disruption of immune tolerance, and metabolic adaptation. By integrating evidence from reproductive biology, immunology, metabolism and pain research, we highlight PRL-PRLR signaling as a context-dependent immunoendocrine regulatory system rather than a uniform pathogenic driver. Defining how this axis operates in distinct tissue microenvironments, disease stages and responsive cell populations may help refine disease stratification and support the development of targeted therapeutic
strategies for gynaecological and female-prevalent diseases.

Communication Author：XIAO Rui-Ping , Email:xiaor@pku.edu.cn