Butyric acid regulates progesterone and estradiol secretion via cAMP signaling pathway in porcine granulosa cells

Abstract Butyric acid (BA), one of the short chain fatty acids (SCFAs), has positive actions on the metabolism, inflammation, etc. However, whether it influences the reproductive physiology and if so the detail mechanism involved has not yet been determined. In this study, the porcine granulosa cells (PGCs) were treated with gradient concentrations of BA. After 24 h culture, 0.05 mM BA significantly stimulated the progesterone (P 4 ) secretion ( P   0.05), 5 mM and 10 mM BA significantly inhibited the P 4 secretion ( P   0.05). Simultaneously, BA up-regulated the estradiol (E 2 ) secretion in a dose dependent manner, 5 mM and 10 mM BA significantly promoted the E 2 level ( P   0.05). In addition, 10 mM BA significantly promoted the G-protein-coupled receptor 41/43 mRNA ( P   0.05). Interestingly, 5 mM BA treatment significantly down-regulated cyclic adenosine monophosphate (cAMP) content ( P   0.05), steroidogenic acute regulatory (StAR), steroidogenic factor 1 (SF1), P450scc in the mRNA and/or protein level ( P   0.05), and these actions were reversed by cAMP activator forskolin (FK). Moreover, the co-treatment of 5 mM BA and bupivacaine (BPC, the cAMP inhibitor) significantly accumulated the inhibition action of BPC on cAMP, the secretion of P 4 , and the abundance of StAR mRNA ( P   0.05), inhibited the up-regulation of 5 mM BA on the E 2 secretion ( P   0.05). Further, the Global Proteome and KEGG pathway analysis found that 5 mM BA significantly up-regulated the I3LM80 proteins ( P   0.05), which is involved in the steroid biosynthesis signaling pathway. 5 mM BA significantly decreased the F2Z5G3 protein level ( P   0.05), and the cAMP signaling pathway. In conclusion, present findings for the first time demonstrated that BA could regulate the P 4 and E 2 hormone synthesis in PGCs via the cAMP signaling pathway.