Lactate-induced effects on bovine granulosa cells are mediated via PKA signaling

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.