Inhibition of small ubiquitin-related modifier-1 expression by luteinizing hormone receptor stimulation is linked to induction of progesterone receptor during ovulation in mouse granulosa cells.

The small ubiquitin-related modifier-1 (SUMO-1) is a member of a family of ubiquitin-related proteins that have effects on several important physiological functions, including reproduction. However, the regulation of SUMO-1 expression and functional distribution of SUMO-1 in vivo remain poorly understood. In the present study, we show that SUMO-1 protein is widely expressed in various tissues. In the ovary, the expression of SUMO-1 protein is suppressed around ovulation, in both the whole ovary and the granulosa cells, after gonadotropin treatment. Additionally, when the ovulatory signal, the endogenous LH surge, is blocked in vivo by pentobarbitone sodium, the expression of SUMO-1 protein in granulosa cells is increased. This effect is reversed when the missing endogenous LH surge is substituted by human chorionic gonadotropin treatment. Our findings provide the first evidence that inhibition of SUMO-1 expression is regulated by LH receptor stimulation in granulosa cells concomitant with ovulation in the mouse ovary. Furthermore, the levels of SUMO-1 protein are increased in granulosa cells treated with progesterone receptor (PR) antagonists both in vivo and in vitro, demonstrating that SUMO-1 expression is regulated by functional PR. SUMO-1 interacts with nuclear receptors in vitro, and LH receptor-mediated induction of PR is crucial for ovulation. SUMO-1 and PR are coexpressed and can be coprecipitated, providing additional evidence for a direct interaction between SUMO-1 and PR in periovulatory granulosa cells in vivo. These results suggest that a functional link between SUMO-1 and PR is of physiological importance for the local modulation of PR-mediated events in the ovary.