Kynurenine, a derivative of tryptophan, inhibits progesterone biosynthesis in porcine granulosa luteal cells through Aryl hydrocarbon receptor-mediated downregulation of GATA-binding protein 4, 6, and CCAAT/enhancer-binding protein beta

Kynurenine (KYN) is a primary tryptophan derivative found in the human body and fermented foods. Previous studies have shown that KYN is an aryl hydrocarbon receptor (AHR) agonist and is important in regulating various physiological activities, including female reproduction. Progesterone is a vital steroid hormone that facilitates embryo implantation and maintains pregnancy. However, whether KYN affects its biosynthesis remains unclear. To gain understanding, in vitro luteinized porcine granulosa luteal (pGL) cells were treated with KYN. The results showed that KYN disrupted progesterone biosynthesis by decreasing the expression of steroidogenic acute regulatory protein (STAR) and 3beta-hydroxysteroid dehydrogenase (HSD3B) in pGL cells. In addition, the expression of three transcription factors of STAR and HSD3B (GATA4, GATA6, and CEBPB) decreased after KYN treatment. Furthermore, the AHR blockade results showed comparable effects to those of KYN treatment, and subsequent knockdown experiments confirmed these results. These findings suggest that KYN inhibits progesterone biosynthesis in pGL cells by downregulating GATA4, GATA6, and CEBPB expression through AHR. Thus, our results showed for the first time a previously unknown connection between KYN and progesterone biosynthesis.