Alteration of the PI3K/Akt signaling pathway by swainsonine affects 17β-Estradiol secretion in ovary cells

Abstract

BackgroundThe ingestion of locoweed that contains the toxic indolizidine alkaloid swainsonine (SW) disrupts ovarian function, accompanied by delayed estrus, increased estrous cycle length, delayed conception, and abortion. GoalsThe direct effects of SW on ovary cell steroidogenesis remain unclear. Materials and methodsIn this study, Chinese hamster ovary (CHO) cells were used to investigate the effects of SW on estradiol (E2) secretion and cell viability and the mechanisms involved in these processes. ResultsCHO cells were treated with SW. 17 β-Estradiol mRNA expression was decreased in the SW group compared to that in the control group. Various concentrations of E2 and SW were added to cultured cells for 12 h and 36 h. Compared to the control group cells, CYP19A1 expression was decreased in the SW and SW + E2 treatment groups at 12 h and 36 h (P < 0.05). This showed that SW mainly inhibits the last step of estrogen synthesis. When CHO cells were treated with SW, the p-Akt protein levels were significantly decreased compared to that in the control group cells at 12 h and 36 h (P < 0.05). However, the p-Akt expression in the SW + E2 group was not significantly different compared to that in the control group cells (P > 0.05). When CHO cells were treated with SW and SW + E2, the PI3K protein levels were significantly down-regulated compared to that in the control group cells at 12 h and 36 h. ConclusionTaken together, these studies demonstrate that SW is an inhibitor of PI3K/Akt signaling pathway. However, SW blocked PI3K activation in estrogen induction without blocking p-Akt activation in CHO cells. Therefore, SW + E2 blocked upstream but did not affect the downstream of the PI3K/Akt signaling pathway.