Gelatinase and Proteoglycanase Activity during the Periovulatory Period in the Rat1

Abstract

Gelatinase and proteoglycanase are metalloproteinases that govern extracellular matrix remodeling. In the present study, immature rats were primed with eCG (20 IU) and hCG (10 IU). Ovarian gelatinase and proteoglycanase activity were determined at the time of hCG administration (0 h) as well as 4, 8, and 12 h later. Gelatinase and proteoglycanase were extracted by homogenization in Triton and by heating (i.e., heat extraction). An aliquot of the heat extract was reduced and alkylated to destroy metalloproteinase inhibitors. Heat extracts not reduced and alkylated showed low levels of gelatinase and proteoglycanase activity that did not change at the different time points. However, with reduction and alkylation, gelatinolysis increased approximately 4-fold (p less than 0.05) at 4 h, 8 h, and 12 h after hCG priming. Proteoglycanase activity increased approximately 2-fold (p less than 0.05) between 0 and 8 h and declined at 12 h after hCG. The ovarian gelatinolytic activity was due to a metalloproteinase as demonstrated by the inhibition of enzyme activity by phenanthroline and EDTA (97.1 +/- 0.7% and 97.4 +/- 0.6% inhibition respectively). Proteoglycanase activity was not inhibited by phenanthroline (11.5 +/- 3.5%), suggesting that the enzyme activity was not specifically a metal-dependent enzyme. Gelatin gel zymography of the ovarian extracts demonstrated four predominant and distinct gelatin-degrading enzymes of 78, 72, 66, and 62 kDa, similar to the size of gelatinase. The present findings demonstrate a periovulatory increase in ovarian gelatinolytic and proteglycanase activity that may play a pivotal role in connective tissue remodeling associated with ovulation.

Stromal-epithelial interaction mediates steroidal regulation of metalloproteinase expression in human endometrium.

“…MMPs are involved in extracellular matrix turnover during many reproductive processes (8)(9)(10)(11)(12)(13)(14), as well as during normal nonreproductive functions (15)(16)(17). These potent enzymes also play an important role in the pathological process of tumor invasion and metastasis (18)(19)(20)(21)(22) …”

Molecular regulators of resolution of inflammation: potential therapeutic targets in the reproductive system

“…This is probably to be mediated at least in part by the highly expressed glucocorticoid effector ANXA1. Resolution signalling could act to terminate ovulation-associated extracellular Resolution pathways in reproductive processes matrix breakdown by MMPs, levels of which decrease following a peak at ovulation (Curry et al 1992). Resolution mediators may also contribute to the unusual scarless healing observed in post-ovulatory surface epithelia (as well as post-menstrual endometrium).…”

Proteasomes and Proteasome Activator 200 kDa (PA200) Accumulate on Chromatin in Response to Ionizing Radiation

“…TIMPs inhibit MMPs to facilitate tightly controlled tissue remodeling and other biological functions. A 1:1 stoichiometric balance of these enzymes and their inhibitors is required for normal follicular development, ovulation, formation and regression of the corpora lutea (CL), embryo development, and embryo implantation [24][25][26][27][28][29][30][31][32].…”