Neurotensin: A novel mediator of ovulation?
Neurotensin: A novel mediator of ovulation?
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DOI：
10.1096/fj.202002547rr
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Duffy DM
中科院分区：
文献类型：
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作者：
Campbell GE;Bender HR;Parker GA;Curry TE Jr;Duffy DM
周期中期的促黄体生成激素（LH）激增在卵泡内引发一系列事件，最终导致排卵。只有壁颗粒细胞和卵泡膜细胞表达大量LH受体，LH刺激的旁分泌介质在卵泡内传递排卵信号。最近的报道确定了神经肽神经降压素（NTS）作为颗粒细胞的产物。在这里，我们证明，颗粒细胞的NTS表达在猕猴排卵卵泡的主要网站。人绒毛膜促性腺激素（hCG）给药后，颗粒细胞NTS mRNA和蛋白增加，替代LH峰。为了鉴定NTS的排卵作用，将NTS中和抗体注射到排卵前猕猴卵泡中。随后立即给予hCG，48小时后切除卵巢以评估排卵事件。注射对照IgG的卵泡正常排卵。相比之下，75%的NTS抗体注射卵泡未能排卵，包含卵母细胞被困在未破裂的出血性卵泡内。血清孕酮无变化。在三种NTS受体中，SORT 1在卵泡颗粒细胞、卵泡膜细胞和内皮细胞中高度表达; NTSR 1和NTSR 2表达水平较低。NTS抗体注射卵泡中过多的血细胞表明血管异常，因此在体外评估了猴卵巢内皮细胞对NTS的反应。NTS刺激内皮细胞迁移和毛细血管芽形成，与NTS在排卵相关的血管重塑中的作用一致。总之，我们确定NTS作为一个可能的旁分泌调解排卵。对NTS合成/反应途径的进一步研究可能会改善不孕症的治疗方法和避孕的新靶点。
The midcycle luteinizing hormone (LH) surge initiates a cascade of events within the ovarian follicle which culminates in ovulation. Only mural granulosa cells and theca cells express large numbers of LH receptors, and LH-stimulated paracrine mediators communicate the ovulatory signal within the follicle. Recent reports identified the neuropeptide neurotensin (NTS) as a product of granulosa cells. Here, we demonstrate that granulosa cells were the primary site of NTS expression in macaque ovulatory follicles. Granulosa cell NTS mRNA and protein increased after human chorionic gonadotropin (hCG) administration, which substitutes for the LH surge. To identify ovulatory actions of NTS, a NTS-neutralizing antibody was injected into preovulatory macaque follicles. hCG administration immediately followed, and ovaries were removed 48 hours later to evaluate ovulatory events. Follicles injected with control IgG ovulated normally. In contrast, 75% of NTS antibody-injected follicles failed to ovulate, containing oocytes trapped within unruptured, hemorrhagic follicles. Serum progesterone was unchanged. Of the three NTS receptors, SORT1 was highly expressed in follicular granulosa, theca, and endothelial cells; NTSR1 and NTSR2 were expressed at lower levels. Excessive blood cells in NTS antibody-injected follicles indicated vascular anomalies, so the response of monkey ovarian endothelial cells to NTS was evaluated in vitro. NTS stimulated endothelial cell migration and capillary sprout formation, consistent with a role for NTS in vascular remodeling associated with ovulation. In summary, we identified NTS as a possible paracrine mediator of ovulation. Further investigation of the NTS synthesis/response pathway may lead to improved treatments for infertility and novel targets for contraception.