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

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.

Effects of peroxisome proliferator-activated receptor activation on gonadotropin transcription and cell mitosis induced by bone morphogenetic proteins in mouse gonadotrope LβT2 cells

“…In their study, FLRG mRNA was weakly detected in the rat pituitary, as shown in LbT2 cells. The finding that FLRG, but not follistatin, expression was increased by activin also provides the possibility of differential regulation of transcription between FLRG and follistatin in pituitary gonadotrope as shown in other tissues such as placenta and skin (Wankell et al 2001, Wang et al 2003. Roles of FLRG in gonadotrope cells need to be further elucidated in the future study.…”

Rab coupling protein (RCP): a novel target of progesterone action in primate endometrium

“…From the large body of available data, it is apparent that several efforts have been made to understand the functions of single molecules and pathways in endometrium exposed to progesterone (Wang et al 2003, Haendler et al 2004, Kitaya et al 2004. However, the approach of scanning the endometrial transcriptomes during the peri-implantation phase, in the presence and absence of progesterone action, promises to offer not only a holistic view of the role of progesterone in endometrial receptivity, but also the identification of novel molecules that have never been investigated for their role in endometrial receptivity.…”

Evaluation of endometrial activin A secretion for prediction of pregnancy after intrauterine insemination

“…It is now well established that activin A is expressed throughout the endometrial cycle in increasing amounts, with the highest levels during the secretory phase (5)(6)(7)(8)(9)(10), and that the human endometrium also expresses activin A receptors (11,12) and both binding proteins, namely follistatin (FS) (7,12) and follistatin-related gene (FLRG) (13,14). Moreover, activin A is secreted by the human endometrium as decidualization progresses, as supported both by in vitro (15,16) and in vivo (7) evidence.…”