Regulation of A Disintegrin And Metalloproteinase with ThromboSpondin repeats-1 expression in human endometrial stromal cells by gonadal steroids involves progestins, androgens, and estrogens.
BACKGROUND
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 A Disintegrin And Metalloproteinase with ThromboSpondin repeats (ADAMTS)-1 in human endometrial stroma in vivo suggests that this novel metalloproteinase may contribute to this tightly regulated developmental process.


OBJECTIVE
The objective of the study was to determine whether progesterone (P4), 17beta-estradiol (E2), or the nonaromatizable androgen dihydrotestosterone (DHT), alone or in combination, is capable of regulating ADAMTS-1 mRNA and protein levels in human endometrial stromal cells in a concentration- and time-dependent manner.


METHODS
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 inhibit specifically 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.
Wen
Jiadi
J
Department of Obstetrics and Gynecology, University of British Columbia, Child and Family Research Institute, Room I3091-950, West 28th Avenue, Vancouver, British Columbia, Canada V5Z 4H4.
Zhu
Hua
H
Murakami
Shuko
S
Leung
Peter C K
PC
MacCalman
Colin D
CD
D051722:ADAM Proteins / Q000378:metabolism*; D000071097:ADAMTS1 Protein; D000328:Adult; D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000502:physiology*; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D011372:Progestins / Q000037:antagonists & inhibitors / Q000502:physiology*; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D000726:Androgen Antagonists; D000728:Androgens; D004338:Drug Combinations; D004967:Estrogens; D012739:Gonadal Steroid Hormones; D011372:Progestins; D013196:Dihydrotestosterone; D004958:Estradiol; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human