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1 May 2002 Dynamic In Vivo Changes in Tissue Inhibitors of Metalloproteinases 1 and 2, and Matrix Metalloproteinases 2 and 9, During Prostaglandin F-Induced Luteolysis in Sheep
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Abstract

Prostaglandin F (PGF) typically initiates a cascade of events that leads to the functional and structural demise of the corpus luteum. A sheep model was used in which a 1-h, systemic infusion of PGF (20 μg/min) is given at midcycle. Such an infusion mimics the onset of spontaneous luteolysis by causing a transient decrease in peripheral plasma progesterone, which reaches a nadir (∼60% of controls) at 8 h but returns to control levels by 16–24 h. We investigated whether PGF also influenced the endogenous protein levels of tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-2, and matrix metalloproteinases, MMP-2 and MMP-9, all of which have been implicated in remodeling of the extracellular matrix (ECM). Corpora lutea (Day 11) were collected at 0 h and at 1, 8, 16, and 24 h post-PGF infusion (n = 3 sheep at each time). Immunoblot analysis revealed an immediate and precipitous decline in TIMP-1 (30 kDa) and TIMP-2 (19 kDa) protein levels (60% and 90%, respectively; P < 0.05) at the 1-h time point and remained depressed at 8 h (P < 0.05). Gelatin zymography and other procedures identified three MMPs (85, 70, and 64 kDa), which were shown to be the latent form of MMP-9 and the active and latent forms of MMP-2, respectively. In contrast to the rapid decrease in TIMP-1 and -2 levels, an increase in MMP-2 activity (165% of controls, P < 0.05) occurred at 8 h, which corresponded to the nadir in plasma progesterone. These early changes in TIMPs and MMPs indicate that alterations in the structure of the ECM by PGF may play a hitherto unsuspected role in the subsequent process of functional luteolysis.

Theresa A. Towle, Paul C. W. Tsang, Robert A. Milvae, Michelle K. Newbury, and John A. McCracken "Dynamic In Vivo Changes in Tissue Inhibitors of Metalloproteinases 1 and 2, and Matrix Metalloproteinases 2 and 9, During Prostaglandin F-Induced Luteolysis in Sheep," Biology of Reproduction 66(5), 1515-1521, (1 May 2002). https://doi.org/10.1095/biolreprod66.5.1515
Received: 10 July 2001; Accepted: 1 December 2001; Published: 1 May 2002
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