Ovulation: a multi-gene, multi-step process

The luteinizing hormone (LH) surge initiates a cascade of proteolytic event s that control ovulation. One of the genes induced by LH is the progesteron e receptor (PR). Because mice with a mutant PR gene (PRKO) fail to ovulate and are infertile, we have used them as a model in which to determine PR ta rget genes that might mediate the ovulatory process. The matrix metalloprot einases (MMPs: MMP2, MMP9, and MMP13) appear to be expressed in ovaries of PRKO mice in a manner similar to that in their wild-type littermates. Howev er, the expression of two other types of proteases, cathepsin L (a member o f the papain family) and ADAMTS-1 (A Disintegrin And Metalloproteinase with Thrombospondin-like motifs), are selectively induced in granulosa cells of preovulatory follicles by the LH surge. Maximal levels of these proteases are observed at 12-16 h after an LH surge, the time of ovulation. Furthermo re, mRNAs encoding cathepsin L and ADAMTS-1 are reduced in the PRKO mice co mpared to their wild-type littermates. These novel observations indicate th at these two proteases regulate some key step(s) controlling ovulation. (C) 2000 Elsevier Science Inc. All rights reserved.