Institute of Reproductive Biology, Research Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, Dummerstorf, 18196, Germany.
Cell Tissue Res. 2022 May;388(2):471-477. doi: 10.1007/s00441-021-03569-7. Epub 2022 Jan 5.
L-lactate acts as a signaling molecule in bovine granulosa cells (GCs). The initiated alterations depend on the transport of L-lactate into the cells via monocarboxylate transporters. In the present study, we further elucidated the intracellular actions of L-lactate and tested whether the PKA signaling pathway is involved. Therefore, we treated cultured bovine GCs with L-lactate and PKA inhibitors H-89 and KT5720, and with an activator of PKA, 6-Bnz-cAMP. L-lactate treatment resulted in decreased estradiol production and downregulation of CYP19A1, FSHR, and LHCGR as well as in the upregulation of the markers of early luteinization PTX3, RGS2, and VNN2. These specific L-lactate effects were almost completely abolished by pre-treatment of the GCs with both inhibitors of PKA signaling. In addition, also the L-lactate-induced upregulation of LDHA and of the monocarboxylate transporters SLC16A1 and SLC16A7 was abolished after PKA inhibition. An activation of the PKA with 6-Bnz-cAMP revealed similar effects on the gene expression like L-lactate alone. In summary, the presented data demonstrate that L-lactate-induced effects on GCs are mediated via PKA signaling thus supporting the role of L-lactate as signaling molecule during the folliculo-luteal transition.
L-乳酸在牛颗粒细胞 (GCs) 中作为信号分子发挥作用。启动的变化取决于 L-乳酸通过单羧酸转运蛋白进入细胞的转运。在本研究中，我们进一步阐明了 L-乳酸的细胞内作用，并测试了 PKA 信号通路是否参与其中。因此，我们用 L-乳酸和 PKA 抑制剂 H-89 和 KT5720 以及 PKA 激活剂 6-Bnz-cAMP 处理培养的牛 GCs。L-乳酸处理导致雌二醇产生减少，CYP19A1、FSHR 和 LHCGR 下调，以及早期黄体化标志物 PTX3、RGS2 和 VNN2 上调。这些特定的 L-乳酸作用几乎完全被 PKA 信号转导的两种抑制剂预处理所消除。此外，PKA 抑制后，L-乳酸诱导的 LDHA 以及单羧酸转运蛋白 SLC16A1 和 SLC16A7 的上调也被消除。用 6-Bnz-cAMP 激活 PKA 会对基因表达产生类似于 L-乳酸单独作用的相似影响。总之，所提供的数据表明，L-乳酸对 GCs 的作用是通过 PKA 信号转导介导的，因此支持 L-乳酸作为卵泡黄体过渡期间的信号分子的作用。
