FIG. 5. LH induction of progesterone receptor (PR) and ADAMTS-1 is essential for ovulation. Expression of ADAMTS-1 is low in pregnant mare serum gonadotropin (PMSG)-treated mice but increases markedly by 8–12 hours after human chorionic gonadotropin (hCG), as shown by in situ hybridization and immunohistochemistry using an antibody to the prodomain of the protein (
-pro ADAMTS-1). Expression of ADAMTS-1 is impaired in the progesterone receptor knockout (PRKO) mice (Robker et al., 2000). The molecular mechanisms by which PR induces ADAMTS-1 appear to involve an indirect pathway, since consensus PR response elements (PRREs) are not found in the proximal ADAMTS-1 promoter. The functional role(s) of ADAMTS-1 remains to be identified, since this protease has multifunctional domains. In other tissues, it is a potent antiangiogenic factor, can degrade aggrecan and brevican, and may impact the integrin system in a manner similar to thrombospondin. Thus, PR and ADAMTS-1 have the potential to regulate many steps in the ovulation process.
