Luteinizing hormone induces ovulation via tumor necrosis factor α-dependent increases in prostaglandin F2α in a nonmammalian vertebrate.

Luteinizing hormone induces ovulation via tumor necrosis factor α-dependent increases in prostaglandin F2α in a nonmammalian vertebrate.
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DOI:
10.1038/srep14210
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发表时间:
2015-09-16
期刊:
影响因子:
4.6
通讯作者:
Planas JV
Planas JV
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Crespo D;Goetz FW;Planas JV

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排卵是由促黄体生成素 (LH) 的排卵前激增诱导的,该激素作用于卵巢,通过刺激卵泡壁的蛋白水解和细胞凋亡而引发排卵前卵泡破裂,从而导致成熟卵母细胞的释放。促炎细胞因子肿瘤坏死因子 α (TNFα) 和前列腺素 (PG) F2α (PGF2α) 参与排卵控制,但它们在介导 LH 促排卵作用中的作用尚未明确。在这里,我们发现 Lh 通过刺激鳟鱼(一种原始硬骨鱼)的 Tnfα 产生来诱导 PGF2α 合成。重组鳟鱼 Tnfα (rTnfα) 和 PGF2α 重现了鲑鱼 Lh (sLh) 对排卵前卵泡壁收缩、蛋白水解和细胞活力丧失以及最终排卵的体外刺激作用。此外,sLh 的所有促排卵作用均被 Tnfα 分泌或 PG 合成抑制所阻断,rTnfα 的所有作用均被 PG 合成抑制剂阻断。因此,我们提供的证据表明,PGF2α 产生的 Tnfα 依赖性增加对于 Lh 的促排卵作用是必要的。这项研究的结果揭示了脊椎动物中 LH 促排卵作用的机制,并且可能对女性不孕症的临床评估很重要。
Ovulation is induced by the preovulatory surge of luteinizing hormone (LH) that acts on the ovary and triggers the rupture of the preovulatory ovarian follicle by stimulating proteolysis and apoptosis in the follicle wall, causing the release of the mature oocyte. The pro-inflammatory cytokine tumor necrosis factor α (TNFα) and prostaglandin (PG) F2α (PGF2α) are involved in the control of ovulation but their role mediating the pro-ovulatory actions of LH is not well established. Here we show that Lh induces PGF2α synthesis through its stimulation of Tnfα production in trout, a primitive teleost fish. Recombinant trout Tnfα (rTnfα) and PGF2α recapitulate the stimulatory in vitro effects of salmon Lh (sLh) on contraction, proteolysis and loss of cell viability in the preovulatory follicle wall and, finally, ovulation. Furthermore, all pro-ovulatory actions of sLh are blocked by inhibition of Tnfα secretion or PG synthesis and all actions of rTnfα are blocked by PG synthesis inhibitors. Therefore, we provide evidence that the Tnfα–dependent increase in PGF2α production is necessary for the pro-ovulatory actions of Lh. The results from this study shed light onto the mechanisms underlying the pro-ovulatory actions of LH in vertebrates and may prove important in clinical assessments of female infertility.