Ovulation: a multi-gene, multi-step process.
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.
Robker
R L
RL
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Russell
D L
DL
Yoshioka
S
S
Sharma
S C
SC
Lydon
J P
JP
O'Malley
B W
BW
Espey
L L
LL
Richards
J S
JS
D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D056668:Cathepsin L; D002403:Cathepsins / Q000235:genetics / Q000494:pharmacology; D051546:Cyclooxygenase 2; D003546:Cysteine Endopeptidases; D019483:Disintegrins / Q000235:genetics / Q000494:pharmacology; D010450:Endopeptidases; D005260:Female; D005786:Gene Expression Regulation; D006107:Granulosa Cells / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000187:drug effects / Q000494:pharmacology; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000235:genetics / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D006080:Ovarian Follicle / Q000166:cytology / Q000378:metabolism; D010060:Ovulation / Q000235:genetics* / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D022762:CCAAT-Enhancer-Binding Proteins; D019483:Disintegrins; D007527:Isoenzymes; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D007986:Luteinizing Hormone; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C489691:Ptgs2 protein, rat; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; C534278:Ctsl protein, mouse; C534280:Ctsl protein, rat; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C486323:Adamts1 protein, mouse; C486324:Adamts1 protein, rat; D020782:Matrix Metalloproteinases; D008666:Metalloendopeptidases