Testosterone inhibits matrix metalloproteinase-1 production in human endometrial stromal cells in vitro

Abstract

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 17b-estradiol (E2), testosterone, or E2Ctestosterone. 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 dosedependent 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.

NSSR1 is regulated by testosterone in the mouse uterus and extensively expressed in endometrial carcinoma

“…Androgen plays an important role in morphological and functional changes of the human endometrium, for example, testosterone can inhibit the expression of MMP-1, a gene that has important roles in implantation and pregnancy [27]. In this study, we studied the effect of androgen on NSSR1 expression in the uterus using testosterone and androgen antagonist, flutamide.…”

Progestins inhibit estradiol-induced vascular endothelial growth factor and stromal cell–derived factor 1 in human endometrial stromal cells

“…A portion of each endometrial specimen in the proliferative phase was confirmed histologically according to the day of the menstrual cycles. ESCs were purified by the standard enzyme digestion method as described previously (21,22). ESCs were cultured in DMEM/F-12 medium supplemented with 10% fetal calf serum (FCS; HyClone), 100 IU/mL penicillin, and 100 mg/mL streptomycin (Invitrogen) at 37 C under an atmosphere of 5% CO 2 in air.…”

Estrogen and selective estrogen receptor modulators regulate vascular endothelial growth factor and soluble vascular endothelial growth factor receptor 1 in human endometrial stromal cells

“…The ESCs were purified by the standard enzyme digestion method as described previously (20,21). The purity of ESCs was determined by morphology and by immunohistochemical staining as described previously (22,23) with markers specific to ESCs (vimentin).…”