Department of Obstetrics and Gynecology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, 300 Community Dr, Manhasset, NY, 11030, USA.
The Clinical Research Center, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA, USA.
Reprod Sci. 2022 Mar;29(3):1001-1019. doi: 10.1007/s43032-021-00797-8. Epub 2021 Nov 18.
As a key mechanism in fibrinolysis and tissue remodeling, the plasminogen activator system has been suggested in the process of endometrial shedding and tissue remodeling. Previous studies have explored the role of estrogen, progesterone, and androgen receptors as well as elements of the renin-angiotensin-aldosterone system in shaping the morphology of the endometrium. This study investigates the distribution and concentrations of the mineralocorticoid receptor, glucocorticoid receptor, tissue plasminogen activator, urokinase plasminogen activator, and plasminogen activator inhibitor-1 within the endometrial stroma, glandular, and endothelial cells of the primate endometrium during artificial menstrual cycles. Our immunohistochemistry quantification shows mineralocorticoid and glucocorticoid receptors are ubiquitously distributed within the macaque endometrium with their patterns of expression following similar fluctuations to urokinase and tissue plasminogen activators particularly within the endometrial vasculature. These proteins are present in endometrial vasculature in high levels during the proliferative phase, decreasing levels during the secretory phase followed by rising levels in the menstrual phase. These similarities could suggest overlapping pathways and interactions between the plasminogen activator system and the steroid receptors within the endometrium. Given the anti-inflammatory properties of glucocorticoids and the role of plasminogen activators in endometrial breakdown, the glucocorticoid receptor may be contributing to stabilizing the endometrium by regulating plasminogen activators during the proliferative phase and menstruation. Furthermore, given the anti-mineralocorticoid properties of certain anti-androgenic progestins and their reduced unscheduled uterine bleeding patterns, the mineralocorticoid receptor may be involved in unscheduled endometrial bleeding.
作为纤维蛋白溶解和组织重塑的关键机制，纤溶酶原激活物系统被认为参与了子宫内膜脱落和组织重塑的过程。先前的研究已经探讨了雌激素、孕激素和雄激素受体以及肾素-血管紧张素-醛固酮系统的元素在塑造子宫内膜形态中的作用。本研究调查了在人工月经周期中，灵长类动物子宫内膜基质、腺体和内皮细胞中醛固酮受体、糖皮质激素受体、组织型纤溶酶原激活物、尿激酶型纤溶酶原激活物和纤溶酶原激活物抑制剂-1的分布和浓度。我们的免疫组织化学定量显示，醛固酮和糖皮质激素受体在猕猴子宫内膜中广泛分布，其表达模式与尿激酶和组织型纤溶酶原激活物相似，特别是在子宫内膜血管中。这些蛋白质在增殖期子宫内膜血管中呈高水平表达，在分泌期表达水平降低，随后在月经期表达水平升高。这些相似性可能表明纤溶酶原激活物系统和子宫内膜中甾体受体之间存在重叠途径和相互作用。鉴于糖皮质激素的抗炎特性以及纤溶酶原激活物在子宫内膜崩解中的作用，糖皮质激素受体可能通过在增殖期和月经期调节纤溶酶原激活物来稳定子宫内膜。此外，鉴于某些抗雄激素孕激素的抗盐皮质激素特性及其不规则子宫出血模式减少，盐皮质激素受体可能参与不规则子宫内膜出血。
