Dynamic in vivo changes in tissue inhibitors of metalloproteinases 1 and 2, and matrix metalloproteinases 2 and 9, during prostaglandin F(2alpha)-induced luteolysis in sheep.

Academic Article


  • Prostaglandin F(2alpha) (PGF(2alpha)) 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(2alpha) (20 microg/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 ( approximately 60% of controls) at 8 h but returns to control levels by 16-24 h. We investigated whether PGF(2alpha) 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(2alpha) 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(2alpha) may play a hitherto unsuspected role in the subsequent process of functional luteolysis.
  • Authors

  • Towle, Theresa A
  • Tsang, Paul
  • Milvae, Robert A
  • Newbury, Michelle K
  • McCracken, John A
  • Status

    Publication Date

  • May 2002
  • Published In


  • Animals
  • Corpus Luteum
  • Dinoprost
  • Female
  • Immunoblotting
  • Kinetics
  • Luteolytic Agents
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase Inhibitors
  • Phenanthrolines
  • Pregnancy
  • Progesterone
  • Protease Inhibitors
  • Sheep
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Digital Object Identifier (doi)

    Pubmed Id

  • 11967218
  • Start Page

  • 1515
  • End Page

  • 1521
  • Volume

  • 66
  • Issue

  • 5