Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, United Kingdom.
Mol Cell Endocrinol. 2012 Jul 25;358(2):208-15. doi: 10.1016/j.mce.2011.10.035. Epub 2011 Nov 9.
Throughout the reproductive years, the rise and fall in ovarian hormones elicit in the endometrium waves of cell proliferation, differentiation, recruitment of inflammatory cells, apoptosis, tissue breakdown and regeneration. The activated progesterone receptor, a member of the superfamily of ligand-dependent transcription factors, is the master regulator of this intense tissue remodelling process in the uterus. Its activity is tightly regulated by interaction with cell-specific transcription factors and coregulators as well as by specific posttranslational modifications that respond dynamically to a variety of environmental and inflammatory signals. Endometriosis, a chronic inflammatory disorder, disrupts coordinated progesterone responses throughout the reproductive tract, including in the endometrium. This phenomenon is increasingly referred to as 'progesterone resistance'. Emerging evidence suggests that progesterone resistance in endometriosis is not just a consequence of perturbed progesterone signal transduction caused by chronic inflammation but associated with epigenetic chromatin changes that determine the intrinsic responsiveness of endometrial cells to differentiation cues.
在生殖期，卵巢激素的升与降会引发子宫内膜的细胞增殖、分化、炎症细胞募集、细胞凋亡、组织分解和再生的波动。孕激素受体是配体依赖性转录因子超家族的成员，它是子宫内这种强烈组织重塑过程的主要调节因子。其活性受到与细胞特异性转录因子和共调节因子的相互作用以及特定的翻译后修饰的严格调节，这些修饰会对各种环境和炎症信号做出动态响应。子宫内膜异位症是一种慢性炎症性疾病，会破坏整个生殖道（包括子宫内膜）中协调一致的孕激素反应。这种现象现在越来越多地被称为“孕激素抵抗”。新出现的证据表明，子宫内膜异位症中的孕激素抵抗不仅仅是慢性炎症引起的孕激素信号转导紊乱的结果，还与决定子宫内膜细胞对分化信号内在反应性的表观遗传染色质变化有关。
