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两种合成的与人促卵泡激素β亚基相对应的肽在小鼠中促进生殖功能。

Two Synthetic Peptides Corresponding to the Human Follicle-Stimulating Hormone β-Subunit Promoted Reproductive Functions in Mice.

机构信息

Isotope Research Laboratory, Biological Engineering and Application Biology Department, Sichuan Agricultural University, Ya'an 625014, China.

Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Animal Nutrition Institute, Sichuan Agricultural University, Ya'an 625014, China.

出版信息

Int J Mol Sci. 2022 Oct 3;23(19):11735. doi: 10.3390/ijms231911735.

Abstract

A follicle stimulating hormone (FSH) is widely used in the assisted reproduction and a synthetic peptide corresponding to a receptor binding region of the human (h) FSH-β-(34−37) (TRDL) modulated reproduction. Furthermore, a 13-amino acid sequence corresponding to hFSH-β-(37−49) (LVYKDPARPKIQK) was recently identified as the receptor binding site. We hypothesized that the synthetic peptides corresponding to hFSH-β-(37−49) and hFSH-β-(34−49), created by merging hFSH-β-(34−37) and hFSH-β-(37−49), modulate the reproductive functions, with the longer peptide being more biologically active. In male or female prepubertal mice, a single injection of 200 μg/g BW ip of hFSH-β-(37−49) or hFSH-β-(34−49) hastened (p < 0.05) puberty, whereas the same treatments given daily for 4 d promoted (p < 0.05) the gonadal steroidogenesis and gamete formation. In addition of either peptide to the in vitro cell cultures, promoted (p < 0.05) the proliferation of primary murine granulosa cells and the estradiol production by upregulating the expression of Ccnd2 and Cyp19a1, respectively. In adult female mice, 200 μg/g BW ip of either peptide during diestrus antagonized the FSH-stimulated estradiol increase and uterine weight gain during proestrus. Furthermore, hFSH-β-(34−49) was a more potent (p < 0.05) reproductive modulator than hFSH-β-(37−49), both in vivo and in vitro. We concluded that hFSH-β-(37−49) and especially hFSH-β-(34−49), have the potential for reproductive modulation.

摘要

卵泡刺激素(FSH)广泛应用于辅助生殖领域,一种与人类(h)FSH-β-(34-37)(TRDL)受体结合区相对应的合成肽调节生殖。此外,最近确定了 hFSH-β-(37-49)(LVYKDPARPKIQK)的 13 个氨基酸序列作为受体结合位点。我们假设,通过融合 hFSH-β-(34-37)和 hFSH-β-(37-49)而创建的 hFSH-β-(37-49)和 hFSH-β-(34-49)对应的合成肽调节生殖功能,其中较长的肽具有更高的生物活性。在雄性或雌性未成熟的小鼠中,单次注射 200μg/g BW ip 的 hFSH-β-(37-49)或 hFSH-β-(34-49)可加速(p<0.05)青春期,而相同的治疗方案连续 4 天给药可促进(p<0.05)性腺类固醇生成和配子形成。将任何一种肽添加到体外细胞培养物中均可促进(p<0.05)初级小鼠颗粒细胞的增殖,并分别通过上调 Ccnd2 和 Cyp19a1 的表达来促进雌二醇的产生。在成年雌性小鼠中,发情期注射 200μg/g BW ip 的任何一种肽均可拮抗发情期 FSH 刺激的雌二醇增加和发情前期子宫增重。此外,hFSH-β-(34-49)在体内和体外都是比 hFSH-β-(37-49)更有效的(p<0.05)生殖调节剂。我们得出结论,hFSH-β-(37-49)和特别是 hFSH-β-(34-49)具有生殖调节的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e75b/9570415/8383a5f001ea/ijms-23-11735-g001.jpg

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