Biosynthesis and secretion of Iutropin in rat gonadotropes treated with swainsonine

Biosynthesis and secretion of LH were investigated using primary cultures of rat gonadotropes following exposure to swainsonine, an inhibitor of N-linked oligosaccharide processing. The inhibition of terminal glycosylation by swainsonine was assessed by the increase in incorporation of [3H]mannose and the decrease of incorporation of [3H]galactose into the trichloroacetic acid-insoluble and anti-ovine LHβ immunoprecipitable fractions. This inhibitor led to an increase in cellular LH with high affinity for concanavalin A and a decrease of LH with less affinity for the lectin, although the cellular LH was not decreased. The swainsonine-treated cells accumulated highly basic LH (pI, 9.6, 10.0) in a time-dependent manner. Although the treated cells showed a decrease in the responsiveness to hormonal stimulation, there were no differenes in the rate and extent of LH secretion induced by maximal stimulation with 100 nmol/I GnRH between the control and treated cells over 24 h. The accumulation of highly basic LH molecules did not result from a decrease in their secretion, since they were secreted in the presence and absence of GnRH. It is concluded that significant changes in N-linked oligosaccharide structure of LH have no effect upon its secretion.