Luteinizing hormone receptor promotes angiogenesis in ovarian endothelial cells of Macaca fascicularis and Homo sapiens†.
Luteinizing hormone receptor promotes angiogenesis in ovarian endothelial cells of Macaca fascicularis and Homo sapiens†.
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黄体生成素受体促进食蟹猴和智人卵巢内皮细胞的血管生成。
DOI：
10.1093/biolre/ioac189
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发表时间：
2023
影响因子：
3.6
通讯作者：
Duffy,DianeM
中科院分区：
文献类型：
--
作者：
Lund,Merete;Pearson,AndrewC;Sage,MeganAG;Duffy,DianeM
卵泡内的血管生成是排卵的重要组成部分。黄体生成素 (LH) 的排卵激增引发新的毛细血管生长，卵泡破裂时血管生成正在顺利进行。 LH 刺激卵泡产生血管生长因子已被证明可以促进排卵卵泡中新毛细血管的形成。 LH 直接作用于卵巢内皮细胞以促进排卵血管生成的可能性尚未得到解决。在这些研究中，从食蟹猴中获得含有排卵卵泡的卵巢，用于卵巢血管内皮细胞的组织学检查，并从排卵卵泡中富集猴卵巢微血管内皮细胞（mOMEC）用于体外研究。 mOMECs表达LHCGR mRNA和蛋白，免疫染色证实体内排卵卵泡内皮细胞中存在LHCGR蛋白。人绒毛膜促性腺激素 (hCG) 是 LHCGR 的配体，在体外可增加 mOMEC 增殖、迁移和毛细血管样芽形成。用 hCG 处理 mOMEC 会增加 cAMP，这是 LHCGR 激活产生的常见细胞内信号。 cAMP 类似物二丁酰 cAMP 在 hCG 不存在的情况下增加 mOMEC 增殖。蛋白激酶 A (PKA) 抑制剂 H89 和磷脂酶 C (PLC) 抑制剂 U73122 均可阻断 hCG 刺激的 mOMEC 增殖，表明多种 G 蛋白可能介导 LHCGR 作用。从健康卵母细胞供体获得的卵巢抽吸物中富集的人卵巢微血管内皮细胞 (hOMEC) 也表达 LHCGR。 hOMEC 也会响应 hCG 进行迁移和增殖。总的来说，这些发现表明 LH 激增可能直接激活卵巢内皮细胞，刺激排卵卵泡的血管生成。
Angiogenesis within the ovarian follicle is an important component of ovulation. New capillary growth is initiated by the ovulatory surge of luteinizing hormone (LH), and angiogenesis is well underway at the time of follicle rupture. LH-stimulated follicular production of vascular growth factors has been shown to promote new capillary formation in the ovulatory follicle. The possibility that LH acts directly on ovarian endothelial cells to promote ovulatory angiogenesis has not been addressed. For these studies, ovaries containing ovulatory follicles were obtained from cynomolgus macaques and used for histological examination of ovarian vascular endothelial cells, and monkey ovarian microvascular endothelial cells (mOMECs) were enriched from ovulatory follicles for in vitro studies. mOMECs expressed LHCGR mRNA and protein, and immunostaining confirmed LHCGR protein in endothelial cells of ovulatory follicles in vivo. Human chorionic gonadotropin (hCG), a ligand for LHCGR, increased mOMEC proliferation, migration and capillary-like sprout formation in vitro. Treatment of mOMECs with hCG increased cAMP, a common intracellular signal generated by LHCGR activation. The cAMP analog dibutyryl cAMP increased mOMEC proliferation in the absence of hCG. Both the protein kinase A (PKA) inhibitor H89 and the phospholipase C (PLC) inhibitor U73122 blocked hCG-stimulated mOMEC proliferation, suggesting that multiple G-proteins may mediate LHCGR action. Human ovarian microvascular endothelial cells (hOMECs) enriched from ovarian aspirates obtained from healthy oocyte donors also expressedLHCGR. hOMECs also migrated and proliferated in response to hCG. Overall, these findings indicate that the LH surge may directly activate ovarian endothelial cells to stimulate angiogenesis of the ovulatory follicle.