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Regular Article |
-Induced Luteolysis1
a Department of Animal Sciences, University of Missouri, Columbia, Missouri 65211
b Departments of Animal Sciences and Physiology, Michigan State University, East Lansing, Michigan 48824
Luteal tissue contains matrix metalloproteinases (MMPs) that cleave specific components of the extracellular matrix (ECM) and are inhibited by tissue inhibitors of metalloproteinases (TIMPs). We previously reported a decrease in luteal TIMP-1 within 15 min of prostaglandin F2
(PGF2
)-induced luteolysis. An increase in the MMP:TIMP ratio may promote ECM degradation and apoptosis, as observed in other tissues that undergo involution. The objectives of these experiments were to determine whether 1) PGF2
affects expression of mRNA encoding fibrillar collagenases (MMP-1 and -13), gelatinases A and B (MMP-2 and -9), membrane type (mt)-1 MMP (MMP-14), stromelysin (MMP-3), and matrilysin (MMP-7), and 2) PGF2
increases MMP activity during PGF2
-induced luteolysis in sheep. Corpora lutea (n = 310/time point) were collected at 0, 15, and 30 min and 1, 2, 4, 6, 12, 24, and 48 h after PGF2
administration. Northern blot analysis confirmed the presence of all MMPs except MMP-9. Expression of mRNA for the above MMPs (except MMP-2) increased significantly (P < 0.05) by 30 min, and all MMPs increased significantly (P < 0.05) by 6 h after PGF2
administration. Expression of MMP-14 mRNA increased significantly (P < 0.05) by 15 min post-PGF2
and remained elevated through 48 h. MMP activity in luteal homogenates (following proenzyme activation and inactivation of inhibitors) was increased significantly (P < 0.05) by 15 min and remained elevated through 48 h post-PGF2
. MMP activity was localized (in situ zymography) to the pericellular area of various cell types in the 0-h group and was markedly increased by 30 min post-PGF2
. MMP mRNA expression and activity were significantly increased following PGF2
treatment. Increased MMP activity may promote ECM degradation during luteolysis.
1 This work is a contribution from the Missouri Agricultural Experiment Station, Journal Series No. 13108, and was supported by USDA grants 98-35203-6282 (to M.F.S.) and 98-35203-6226 (to G.W.S.).
2 Correspondence: Michael F. Smith, Department of Animal Science, 160 Animal Sciences Center, University of Missouri, Columbia, MO 65211. FAX: 573 884 7827; smithmf{at}missouri.edu
3 Current address: Department of Anatomy and Obstetrics/Gynecology, University of California, San Francisco, CA 94143
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