Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Gynecology, Saiseikai Nagasaki Hospital, Nagasaki, Japan.
PLoS One. 2020 Nov 13;15(11):e0242246. doi: 10.1371/journal.pone.0242246. eCollection 2020.
Differential expressions of estrogen/progesterone receptors (ER/PR) and individual component of extracellular matrices derived from fibroid are reported. Information on the pattern of change in ER/PR expression and amount of tissue fibrosis after hormonal treatment is unclear. We investigated pattern of change in ER/PR expression and percentage of tissue fibrosis in different uterine leiomyomas after gonadotropin-releasing hormone agonist (GnRHa) treatment. Biopsy specimens from fibroids and adjacent myometria were collected after surgery from women with submucosal myoma (SMM, n = 18), intramural myoma (IMM, n = 16) and subserosal myoma (SSM, n = 17). A proportion of women in each group of fibroid underwent treatment with GnRHa for a variable period of 3-6 months. Tissue expression of ER and PR was analyzed by immunohistochemistry. In vitro cell proliferation effect of GnRHa on human umbilical vein endothelial cells (HUVECs) was examined. Distribution of tissue fibrosis was examined by Masson's trichrome staining with computer-captured image analysis of fibrosis derived from different types of fibroid. PR content was significantly higher than ER in tissues derived from GnRHa-untreated women with SMM and SSM (p = 0.04 for both). Comparing to untreated group, GnRHa-treatment significantly decreased either ER or PR expression in different fibroids. Exogenous treatment with GnRHa dose-dependently decreased proliferation of HUVECs. No significant difference was observed in the percentage of fibrosis in tissues collected from GnRHa-treated and -untreated women with fibroids. The distribution of fibrosis in myoma/myometria and occurrence of fibrosis in perivascular area showed an increasing trend with higher age of the women and with larger size of fibroids. Our findings suggest that despite estrogen dependency, higher PR content in GnRHa-untreated group may indicate a potential role of progesterone in leiomyoma growth. Although GnRHa therapy may shrink fibroids and reduce risk of bleeding during surgery, the occurrence of diffuse tissue fibrosis may impair effective reduction of fibroid size after hormonal treatment.
报道了子宫肌瘤中雌激素/孕激素受体（ER/PR）和细胞外基质各成分的差异表达。关于激素治疗后 ER/PR 表达变化模式和组织纤维化程度的信息尚不清楚。我们研究了促性腺激素释放激素激动剂（GnRHa）治疗后不同类型子宫肌瘤中 ER/PR 表达变化模式和组织纤维化程度。从黏膜下子宫肌瘤（SMM，n = 18）、壁间子宫肌瘤（IMM，n = 16）和浆膜下子宫肌瘤（SSM，n = 17）患者的手术标本中收集了肌瘤和邻近子宫肌层的活检标本。每个肌瘤组中的一部分患者接受 GnRHa 治疗，治疗时间为 3-6 个月。通过免疫组织化学分析 ER 和 PR 的组织表达。检测 GnRHa 对人脐静脉内皮细胞（HUVEC）的体外细胞增殖作用。通过 Masson 三色染色检查不同类型肌瘤的组织纤维化分布，并通过计算机捕获图像分析纤维化。在未接受 GnRHa 治疗的 SMM 和 SSM 妇女的组织中，PR 含量明显高于 ER（p = 0.04）。与未治疗组相比，GnRHa 治疗显著降低了不同子宫肌瘤中 ER 或 PR 的表达。外源性 GnRHa 治疗呈剂量依赖性地降低 HUVEC 的增殖。在接受和未接受 GnRHa 治疗的子宫肌瘤妇女的组织中，纤维化百分比无显著差异。在肌瘤/子宫肌层中的纤维化分布和血管周围区域纤维化的发生随着妇女年龄的增长和肌瘤的增大呈增加趋势。我们的研究结果表明，尽管雌激素依赖性，但在未接受 GnRHa 治疗的组中，较高的 PR 含量可能表明孕激素在子宫肌瘤生长中起潜在作用。尽管 GnRHa 治疗可能会缩小肌瘤并减少手术期间出血的风险，但弥漫性组织纤维化的发生可能会影响激素治疗后肌瘤大小的有效减少。
