Abstract: Swainsonine (SW) can cause disorders of reproductive hormones. Gonadotropins are glycoprotein hormones, so they are regulated by N-glycosylation modifications. ɑ-mannosidase, a key enzyme that accelerates the processing of N-glycosylation modifications, can be inhibited by SW. So how does SW affect the structure of N-glycan and the secretion performance of reproductive hormone is unclear. Thus, this test was conducted by intraperitoneal injection of SW exposed mice to establish models of poisoning. The changes of N-glycan structure in their pituitary tissues were detected by MALDI-TOF-MS mass spectrometry; the activity of glycosylase, the level of reproductive hormone, the quantity of reproductive hormone receptors were analyzed. With the extension of injection time, the five composite glycosides of the pituitary glycoprotein in the poisoned group disappeared, and three hybrid glycosides were added. The activities of glycosyltransferase and glycosidase in the poisoned group were significantly decreased. There were further found that the expression levels of gonadotropin receptor, estradiol and progesterone receptor proteins in the poisoned group were significantly lower than those in the control group, and the secretion levels of reproductive hormones were also significantly decreased. SW can significantly inhibit the activity of N-glycan glycosylase and cause changes of normal N-glycan structure; it has a negative influence on the activities of gonadotropins and their receptors, causing the regulation of downstream steroid hormone secretion out of balance, and eventually, reproductive hormone regulation can be disrupted.

Key words: swainsonine, N-glycan glycosylation, glycosylase, gonadotropin, steroid hormone