Time-dependent relationship between the estrogen receptors and the matrix metalloproteinases following deciduoma induction in rats

The purpose of this study was to investigate time-related interactions between the estrogen receptors, mediators of steroidal regulation of uterine growth, and an extracellular regulatory enzyme, the matrix metalloproteinases (MMPs) engaged in connective tissue degradation and remodeling that are fundamental to implantation and placentation. Pseudopregnant rats, in which the decidual response, the basis for decidualization, was surgically induced on day 4 of pseudopregnancy (PG), were sacrificed on PG days 3, 6, 9, and 15 for retrieval of uterine tissues for assays: the radioligand binding assay for the estrogen receptors and substrate zymography for the MMPs. Following increases on PG day 3, there were time-dependent decreases in the cytosolic low and high capacity estrogen receptors during deciduoma development (PG days 6-9) and regression (PG day 15) in both the endometrium and myometrium. Moreover, whereas the low capacity estrogen receptor levels were only slightly decreased (PG days 6-15), the high capacity receptors were reduced on day 6 (P < 0.001) and were completely diminished during PG days 9 and 15. In contrast, the MMPs (92 and 72 kDa) activities were increased from PG days 6-15 (P < 0.05) over the pre-decidual induction values on PG day 3 in both uterine compartments. The results suggest that deciduoma induction can modulate the concentration of cytosolic estrogen receptor subtypes and MMP activities in rats. The inverse time-dependent interrelationship between these cellular and extracellular components during deciduoma development and regression imply that the remodeling role of the MMPs may be enhanced by the reduced cytosolic estrogen receptor/estrogen action. (C) 1998 Elsevier Science Inc. All rights reserved.