Alteration of glycan structures by swainsonine affects steroidogenesis in bovine luteal cells

The indolizidine alkaloid swainsonine (SW), a potent inhibitor of Golgi α-mannosidase II, is considered the primary toxicant in locoweeds causing toxicity syndrome known as locoism in livestock. Locoweed consumption decreases serum progesterone concentration and causes serious disorders in reproductive functions of livestock. However, direct effects of SW on luteal steroidogenic cells (LSCs) remain unclear. In the present study, we investigated the effect of N-glycan processing inhibition by SW on progesterone production and viability in cultured bovine LSCs. Swainsonine (0.1 μg/mL) fully inhibited glycosylation in the LSCs, but it had no effect on viability and progesterone production in the LSCs. Luteinizing hormone is known to promote progesterone production and expressions of steroidogenic acute regulatory protein and scavenger receptor type B class I. Pretreatment of LSCs with SW suppressed each of these effects, possibly by inhibiting LH receptor activity. These results suggest that SW inhibits N-glycan processing, which attenuates LH receptor activity, which, in turn, reduces progesterone production by CL.