Follistatin-Related Gene (FLRG) Expression in Human Endometrium: Sex Steroid Hormones Regulate the Expression of FLRG in Cultured Human Endometrial Stromal Cells

Hua-Qin Wang, Koichi Takebayashi, Kunihiro Tsuchida, Masaki Nishimura, Yoichi Noda
In: The Journal of Clinical Endocrinology & Metabolism · 2003 · vol. 88(9) , pp. 4432–4439 · doi:10.1210/jc.2002-021758 · PMID:12970321 · W2127352548
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Human endometrial FLRG mRNA and protein are expressed across the menstrual cycle and pregnancy, with sex steroids inducing FLRG expression in cultured stromal cells.

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Abstract

Follistatin-related gene (FLRG) encodes a novel secreted glycoprotein that is highly homologous to follistatin and binds activins and bone morphogenetic proteins, members of the TGF beta superfamily of growth/differentiation factors. FLRG protein inhibits activin-induced and bone morphogenetic protein-2-induced transcriptional responses in a dose-dependent manner, and its mRNA is abundantly expressed in human placenta, heart, aorta, testis, and adrenal gland. In this study we showed that FLRG mRNA was expressed in human endometrium across the menstrual cycle and in decidua of early pregnancy. In the proliferative phase of the menstrual cycle, FLRG protein was detected predominantly in the cytoplasm of endometrial epithelium. In the secretory phase and in early pregnancy, it was also detected in the nuclei of endometrial stromal cells. Using in vitro decidualization model, we demonstrated that 17 beta-estradiol plus progesterone, but not 17 beta-estradiol or progesterone alone, induced FLRG expression significantly. These results suggest that FLRG expression in endometrial stromal cells is regulated by the concerted action of ovarian steroid hormones via decidualization, and FLRG protein may participate in the regulation of stromal cell decidualization as a binding protein for members of TGF beta superfamily.

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