In addition, the Esr1knockut male mice are sterile and show atrophic testes with a loss of germ cells in the dilated seminiferous tubules, consistent with the phenotypes observed in Lgr4-knock male mice. Therefore, the testicular effects of Lgr4 on controlling the Esr1 expression might potentially EX 527 explain the consequence of infertility in CP-690550 Lgr4-null mice. In addition, although expression of Aqp1 has been reported to be abundant in the epididymis, several studies have also demonstrated it can be detected locally in some specific cells of the testis. For example, the Aqp1 protein signal can be detected in the endothelium of the blood vessels in the testicular interstitium of cats. Similar results have also been reported in monkeys, rats and mice. These might explain why we can observe the expressional change of Aqp1 in Lgr4-ED treated mice. Taken together, these findings suggest that Lgr4-ED will be useful as a tool when exploring the possible physiological functions of Lgr4 in various organs. Taking advantage of this possibility, we used Lgr4-ED to study the potential roles of Lgr4 in the ovary. Although Lgr4-null female mice also show significant reduction in fertility, no obvious histological change has ever been reported in the ovary. By using superovulated female rats for the Lgr4-ED injection, we showed that Lgr4-ED had suppressive effects on the PMSG induction of Lhr expression and on progesterone production in the ovary. However, we also noticed that changes of steroidogenic gene levels in Lgr4-ED treated animals are not consistent with the dramatic down-regulation of progesterone production. This might be explained by the following reasons. It has been known that the levels of steroidogenic genes can be elevated immediately in the gonadotropin-primed superovulated rodents but then gradually decrease along with the time. Taking Star as an example, the Star transcript in the superovulated rats has been reported to reach the highest level at 6 hr after PMSG injection and return to almost the basal level after two days.