Context. Gonadal steroids are key regulators of the extracellular matrix remodeling events that occur in the human endometrium during each menstrual cycle. The spatiotemporal expression of ADAMTS-1 in human endometrial stroma in vivo suggests that this novel metalloproteinase may contribute to this tightly regulated developmental process.

Objective. To determine whether progesterone (P4), 17-estradiol (E2), or the nonaromatisable androgen, dihydrotestosterone (DHT), alone or in combination, are capable of regulating ADAMTS-1 mRNA and protein levels in human endometrial stromal cells in a concentration- and time-dependent manner.

Design. A real-time quantitative PCR strategy and Western blotting were used to examine ADAMTS-1 mRNA and protein expression levels in primary cultures of human endometrial stromal cells.

Results. P4 and DHT but not E2 increased the levels of the ADAMTS-1 mRNA transcript and protein species (110 kDa) present in endometrial stromal cells in vitro in a concentration- and time-dependent manner. A combination of P4 and DHT resulted in an additional increase in stromal ADAMTS-1 expression whereas E2 attenuated the regulatory effects of P4 and DHT in a concentration-dependent manner. The antisteroidal compounds, mifepristone (RU486) and hydroxyflutamide, were also found to specifically inhibit the P4- and DHT-mediated increase in ADAMTS-1 mRNA and protein expression levels in these primary cell cultures in a concentration-dependent manner, respectively.

Conclusions. These studies demonstrate that progestins, androgens and estrogens, alone and in combination, have distinct regulatory effects on ADAMTS-1 mRNA and protein expression levels in human endometrial stromal cells in vitro.