Maillard Virginie, Elis Sébastien, Desmarchais Alice, Hivelin Céline, Lardic Lionel, Lomet Didier, Uzbekova Svetlana, Monget Philippe, Dupont Joëlle
UMR85 PRC, INRA, CNRS, IFCE, Université de Tours, 37380 Nouzilly, France.
Reprod Fertil Dev. 2017 Nov;29(12):2479-2495. doi: 10.1071/RD16301.
Visfatin and resistin appear to interfere with reproduction in the gonads, but their potential action at the hypothalamic-pituitary level is not yet known. The aim of the present study was to investigate the mRNA and protein expression of these adipokines in murine gonadotroph cells and to analyse the effects of different concentrations of recombinant mouse visfatin and resistin (0.01, 0.1, 1 and 10ngmL) on LH secretion and signalling pathways in LβT2 cells and/or in primary female mouse pituitary cells. Both visfatin and resistin mRNA and protein were found in vivo in gonadotroph cells. In contrast with resistin, the primary tissue source of visfatin in the mouse was the skeletal muscle, and not adipose tissue. Visfatin and resistin both decreased LH secretion from LβT2 cells after 24h exposure of cells (P<0.03). These results were confirmed for resistin in primary cell culture (P<0.05). Both visfatin (1ngmL) and resistin (1ngmL) increased AMP-activated protein kinase α phosphorylation in LβT2 cells after 5 or 10min treatment, up to 60min (P<0.04). Extracellular signal-regulated kinase 1/2 phosphorylation was transiently increased only after 5min resistin (1ngmL) treatment (P<0.01). In conclusion, visfatin and resistin are expressed in gonadotroph cells and they may affect mouse female fertility by regulating LH secretion at the level of the pituitary.
内脂素和抵抗素似乎会干扰性腺的生殖功能，但其在下丘脑 - 垂体水平的潜在作用尚不清楚。本研究的目的是调查这些脂肪因子在小鼠促性腺激素细胞中的mRNA和蛋白质表达，并分析不同浓度的重组小鼠内脂素和抵抗素（0.01、0.1、1和10 ng/mL）对LβT2细胞和/或原代雌性小鼠垂体细胞中促黄体生成素（LH）分泌及信号通路的影响。在促性腺激素细胞的体内实验中发现了内脂素和抵抗素的mRNA及蛋白质。与抵抗素不同，小鼠体内内脂素的主要组织来源是骨骼肌，而非脂肪组织。细胞暴露24小时后，内脂素和抵抗素均降低了LβT2细胞的LH分泌（P<0.03）。原代细胞培养中抵抗素的实验结果也证实了这一点（P<0.05）。处理5或10分钟直至60分钟后，内脂素（1 ng/mL）和抵抗素（1 ng/mL）均增加了LβT2细胞中AMP激活的蛋白激酶α的磷酸化水平（P<0.04）。仅在抵抗素（1 ng/mL）处理5分钟后，细胞外信号调节激酶1/2的磷酸化水平短暂升高（P<0.01）。总之，内脂素和抵抗素在促性腺激素细胞中表达，它们可能通过调节垂体水平的LH分泌来影响小鼠雌性生育能力。
