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.
MeSH terms
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ADAM Proteins
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ADAMTS1 Protein
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Animals
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CCAAT-Enhancer-Binding Proteins / genetics
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Cathepsin L
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Cathepsins / genetics
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Cathepsins / pharmacology
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Cyclooxygenase 2
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Cysteine Endopeptidases
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Disintegrins / genetics
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Disintegrins / pharmacology
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Endopeptidases*
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Female
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Gene Expression Regulation
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Granulosa Cells / metabolism
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Isoenzymes / genetics
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Isoenzymes / pharmacology
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Luteinizing Hormone / drug effects
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Luteinizing Hormone / pharmacology
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Matrix Metalloproteinases / drug effects
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Matrix Metalloproteinases / pharmacology
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Metalloendopeptidases / genetics
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Metalloendopeptidases / pharmacology
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Mice
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Mice, Knockout
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Ovarian Follicle / cytology
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Ovarian Follicle / metabolism
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Ovulation / genetics*
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Ovulation / physiology*
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Promoter Regions, Genetic
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Prostaglandin-Endoperoxide Synthases / genetics
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Prostaglandin-Endoperoxide Synthases / pharmacology
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RNA, Messenger / metabolism
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Rats
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Receptors, Progesterone / genetics
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Receptors, Progesterone / metabolism
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Transfection
Substances
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CCAAT-Enhancer-Binding Proteins
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Disintegrins
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Isoenzymes
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RNA, Messenger
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Receptors, Progesterone
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Luteinizing Hormone
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Ptgs2 protein, mouse
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Cyclooxygenase 2
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Prostaglandin-Endoperoxide Synthases
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Ptgs2 protein, rat
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Cathepsins
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Endopeptidases
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Cysteine Endopeptidases
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Cathepsin L
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Ctsl protein, mouse
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Ctsl protein, rat
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ADAM Proteins
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ADAMTS1 Protein
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Adamts1 protein, mouse
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Adamts1 protein, rat
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Matrix Metalloproteinases
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Metalloendopeptidases