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Ovulation: a multi-gene, multi-step process
R L Robker1, D L Russell, S Yoshioka
1Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Abstract:
The luteinizing hormone (LH) surge initiates a cascade of proteolytic events that control ovulation. One of the genes induced by LH is the progesterone 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 target genes that might mediate the ovulatory process. The matrix metalloproteinases (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. However, the expression of two other types of proteases, cathepsin L (a member of 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. Furthermore, mRNAs encoding cathepsin L and ADAMTS-1 are reduced in the PRKO mice compared to their wild-type littermates. These novel observations indicate that these two proteases regulate some key step(s) controlling ovulation.
Insights
The luteinizing hormone (LH) surge triggers ovulation by inducing proteases. Progesterone receptor (PR) knockout mice reveal cathepsin L and ADAMTS-1 are crucial for ovulation, highlighting their role in reproductive processes.
Area of Science:
- Reproductive Biology
- Molecular Endocrinology
- Protease Function
Background:
- Ovulation is a complex process controlled by hormonal signaling, including the luteinizing hormone (LH) surge.
- The progesterone receptor (PR) plays a critical role in ovulation, as evidenced by infertility in PR knockout (PRKO) mice.
- Identifying PR target genes is essential for understanding the molecular mechanisms governing ovulation.
Purpose of the Study:
- To identify progesterone receptor (PR) target genes involved in the ovulatory process.
- To investigate the role of specific proteases, cathepsin L and ADAMTS-1, in LH-induced ovulation.
- To utilize PRKO mice as a model to elucidate PR-mediated ovulatory pathways.
Main Methods:
- Comparative analysis of protease gene expression (MMPs, cathepsin L, ADAMTS-1) in wild-type and PRKO mouse ovaries.
- Induction of protease expression by the LH surge in preovulatory follicles.
- Quantification of cathepsin L and ADAMTS-1 mRNA levels in PRKO versus wild-type littermates.
Main Results:
- Matrix metalloproteinases (MMPs) expression was similar in PRKO and wild-type mice.
- Cathepsin L and ADAMTS-1 expression were selectively induced by the LH surge in granulosa cells of preovulatory follicles.
- mRNA levels for cathepsin L and ADAMTS-1 were significantly reduced in PRKO mice compared to wild-type littermates.
Conclusions:
- Cathepsin L and ADAMTS-1 are novel PR target genes induced by the LH surge.
- These proteases play a critical role in regulating key steps controlling ovulation.
- The findings provide new insights into the molecular control of ovulation and female fertility.
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