Gonadal steroids regulate the expression of aggrecanases in human endometrial stromal cells in vitro

Abstract

The human endometrium undergoes cyclic change during each menstrual cycle in response to gonadal steroids. Proteolysis of endometrial extracellular matrix (ECM) is necessary to prepare this dynamic tissue for pregnancy. Proteolytic enzymes such as matrix metalloproteinase (MMP) and closely related a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) have been assigned key roles in the highly regulated cyclic remodelling of the endometrial ECM. We have previously shown that ADAMTS-1 undergoes spatiotemporal changes in human endometrial stromal cells under the regulation of gonadal steroids. This suggests that other ADAMTS subtypes, known as aggrecanases, may contribute to the ECM remodelling events that occur in female physiological cycles and in preparation for pregnancy. To determine whether progesterone (P4), 17β-estradiol (E2), or dihydrotestosterone (DHT), alone or in combination, are capable of regulating ADAMTS-4, -5, -8 or -9 expression in human endometrial stromal cells in vitro. Real-time quantitative PCR and Western blot analysis were used to measure ADAMTSs mRNA and protein levels in primary cultures of human endometrial stromal cells (n = 12). P4, DHT but not E2 have regulatory effects on ADAMTS-8, -9 and -5 expression. Combined treatment with gonadal steroids did not show any synergistic or antagonistic effects. However, the synthetic steroid antagonists RU486 and hydroxyflutamide specifically inhibited the P4- or DHT-mediated regulatory effects on ADAMTS expression. These studies provide evidence that the regulation of aggrecanases by gonadal steroids in human endometrial stromal cells may play an important role during decidualization.

Prognostic Value of ADAMTS Proteases and Their Substrates in Epithelial Ovarian Cancer

“…The majority of ADAMTS subtypes have been characterized at the structural level, and their expression is associated with pre- and postnatal growth, and onset and progression of cancer, arthritis, Alzheimer's disease, and a number of inflammatory and thrombotic conditions (table 1) [6,7,10,11]. Some ADAMTS subtypes, such as ADAMTS-1, -4, -5, -8, -9, and -15, have been subclassified as aggrecanases because of their ability to cleave large chondroitin sulfate that provides the scaffold for ECM organization in a wide array of tissues [10].…”

“…ADAMTS ( a d isintegrin and m etalloproteinase with t hrombo s pondin motifs) are a family of secreted zinc-dependent metalloproteinases comprising at least 19 genetically distinct members in humans [6,7]. They share homology in the catalytic ADAM metalloprotease and disintegrin domains, but they differ in variable numbers of thrombospondin-like motifs and other carboxyl-terminal domains associated with ECM interaction [6,8,9].…”

The influence of a sustained 10‐day hypoxic bed rest on cartilage biomarkers and subchondral bone in females: The FemHab study

“…There is no discernible pattern to the direction of change as a result of either intervention or through the effects of the hormonal cycle. There is evidence that progesterone plays a role in regulating aggrecan and aggrecanases and therefore it is crucial to monitor and coordinate the menstrual cycle for future work in this area (Wen, Zhu, & Leung, ; Yasuo, Yamaguchi, & Kitaya, ). Yasuo et al () report significant changes in the levels of serum aggrecan as a result of the menstrual cycle with peaks during the mid to late secretory phase compared to the proliferative phase.…”

Molecular characterization of lysyl oxidase‐mediated extracellular matrix remodeling during mouse decidualization

“…MMP‐2 and MMP‐9 are defined to induce trophoblast invasion and play crucial roles in human implantation . Besides MMPs, a disintegrin and metalloproteinase (ADAM) family member ADAM12 and ADAMTS also plays a critical role in the regulation of trophoblast invasion . Taken together, as the crosslinking and degradation enzymes all play critical roles during decidualization, the balanced collaboration among these enzymes might provide the dynamic environment for embryo adhesion and development in different phases during pregnancy.…”