Testosterone inhibits matrix metalloproteinase-1 production in human endometrial stromal cells in vitro.
Androgen receptor (AR) is reported to be expressed in human uterine endometrium, but not much information is available on the role of androgens in human endometrium. The purpose of this study is to investigate the role of androgens in the regulation of matrix metalloproteinase (MMP)-1, which is one of the important MMPs for menstruation and embryo implantation in human endometrium. Human endometrial stromal cells (HESCs) were obtained from human endometrium by enzymatic dissociation method. Purified HESCs were incubated with 17beta-estradiol (E2), testosterone, or E2 + testosterone. Progestins (natural progesterone or medroxyprogesterone acetate) or vehicle (dimethyl sulfoxide) were also added to the media instead of testosterone. Furthermore, hydroxyflutamide (FLU),a specific AR antagonist, was also supplemented to cultured media. The amounts of MMP-1 in cultured media and in HESC lysates were examined by ELISA measurements and western blotting analysis respectively. The expression of ARmRNA in HESCs RNA was analyzed by RT-PCR. Testosterone significantly inhibited MMP-1 in both cultured media and cell lysates in a dose-dependent manner. Progestins also inhibited MMP-1. Furthermore, FLU completely recovered the decrease of MMP-1 induced by testosterone. ARmRNA was detected in all HESCs RNA. The present study demonstrated that the secretion and production of MMP-1 in HESCs in vitro were inhibited by testosterone through androgen receptors in a manner similar to that seen for progesterone. These findings indicate that androgen may play an important role in morphological and functional changes of human endometrium.
Ishikawa
Tomonori
T
Comprehensive Reproductive Medicine, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. t.ishikawa.crm@tmd.ac.jp
Harada
Tatsuya
T
Kubota
Toshiro
T
Aso
Takeshi
T
D000328:Adult; D000726:Androgen Antagonists / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D003864:Depression, Chemical; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005485:Flutamide / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000032:analysis / Q000378:metabolism*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000187:drug effects / Q000201:enzymology; D013739:Testosterone / Q000494:pharmacology*
C410798:AR protein, human; D000726:Androgen Antagonists; D011944:Receptors, Androgen; C014290:hydroxyflutamide; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D005485:Flutamide; D017258:Medroxyprogesterone Acetate; D020781:Matrix Metalloproteinase 1