Ontogenies of messenger RNA encoding tissue inhibitor of metalloproteinases 1 and 2 within bovine periovulatory follicles and luteal tissue.

Tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) are important regulators of extracellular matrix remodeling and also possess growth factor activity. The objective of these studies was to characterize TIMP-1 and TIMP-2 mRNA expression by bovine periovulatory follicles/ corpora hemorrhagica (Experiment 1) and luteal tissue (Experiment 2). In Experiment 1, beef heifers (n = 27) were ovariectomized at-16 (n = 6), 0 (n = 5), 8 (n = 3), 16 (n = 4), 24 (n = 4), or 48 (n = 5) hr relative to a gonadotropin-releasing hormone induced gonadotropin surge (40 hr after prostaglandin F2 alpha-induced luteolysis). Total cellular RNA was isolated from the large steroidogenically active follicle or corpus hemorrhagicum obtained from each animal, and the expression of TIMP-1 and TIMP-2 mRNA was subsequently examined by northern and dot blot analysis. The expression of TIMP-1 or TIMP-2 mRNa did not differ in preovulatory follicles collected at -16 vs. 0 hr. Concentrations of both TIMP-1 and TIMP-2 mRNA (picograms per microgram of tissue DNA) were increased (P < 0.05) at 8 hr postgonadotropin surge, had declined to presurge levels by 24 hr (P < 0.05), and were increased (P < 0.05) in corpora hemorrhagica collected at 48 hr after a gonadotropin surge. In Experiment 2, corpora lutea were collected from beef heifers on Days 4, 10, 15 (n = 4 each), or 19 (n = 3) postestrus (Day 0 = estrus). Concentrations of TIMP-1 mRNA (picograms per microgram of tissue DNA) were greater in corpora lutea collected on Day 4 (P < 0.05) vs. Day 10, 15, or 19. Concentrations of TIMP-2 mRNA increased (P < 0.05) from Day 4 to 15 and decreased (P < 0.05) by Day 19. We conclude that: 1) during the periovulatory period, the ontogenies of TIMP-1 and TIMP-2 mRNA expression are similar, whereas 2) during luteal phase, TIMP-1 mRNA expression is maximal during the early luteal phase, whereas concentrations of TIMP-2 mRNA peak during the midluteal phase. TIMP-1 and TIMP-2 may play important roles in the regulation of extracellular matrix remodeling during the periovulatory period and the subsequent luteal phase.