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

Abstract

Abstractl-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.