Induction of G protein-coupled estrogen receptor (GPER) and nuclear steroid hormone receptors by gonadotropins in human granulosa cells

Abstract

Estradiol and progesterone mediate their actions by binding to classical nuclear receptors, estrogen receptor α (ERα) and estrogen receptor β (ERβ) and progesterone receptor A and B (PR-A and PR-B) and the non-classical G protein-coupled estrogen receptor (GPER). Several animal knock-out models have shown the importance of the receptors for growth of the oocyte and ovulation. The aim of our study was to identify GPER in human granulosa cells (GC) for the first time. Moreover, the effect of different doses of gonadotropins on estrogen and progesterone receptors in the human ovary should be investigated as follicle stimulating hormone (FSH) and luteinizing hormone (LH) are also responsible for numerous mechanisms in the ovary like induction of the steroid biosynthesis. Human GC were cultured in vitro and stimulated with different doses of recombinant human FSH or LH. Receptor expression was analyzed by immunocytochemistry and quantitative real-time RT-PCR. GPER could be identified for the first time in human GC. It could be shown that high concentrations of LH increase GPER protein expression. Furthermore FSH and LH increased ERβ, PR-A and PR-B significantly on protein level. These findings were verified for high doses of FSH and LH on mRNA level. ERα was not affected with FSH or LH. We assume that gonadotropins induce GPER, ERβ and PR in luteinized granulosa cells.

Estrogen biology: New insights into GPER function and clinical opportunities

“…Luteinizing hormone was recently shown to regulate GPER expression at the mRNA and protein level in human granulosa cells (Pavlik et al, 2011). Interactions and cross-talk between GPER and growth factor receptors, particularly EGFR and IGFR, have been recently summarized by Maggiolini and colleagues (Bartella et al, 2012; Lappano et al, 2013).…”

Expression of the oestrogen receptor GPER by testicular peritubular cells is linked to sexual maturation and male fertility

“…It supports the unexpected results related to peritubular cells. The specificity of the antiserum was further substantiated by results of Western blotting experiments using human granulosa cells, recently reported to express GPER (Pavlik et al ., 2011; results not shown). To our knowledge GPER expression by the smooth-muscle-like peritubular cells of the testis has not been reported in previous studies using different antibodies and immunohistochemistry.…”

Recent progress in histochemistry and cell biology

“…Recently a non-classical G protein-coupled estrogen receptor (GPER) was described (Revankar et al 2005;Thomas et al 2005b), indicating that estradiol can act rapidly independent of transcription. With no data available regarding the expression of GPER in human granulosa tissue and cells, Pavlik et al (2011) addressed this issue and could identify in their study GPER in human granulosa cells (GC). The authors additionally demonstrated that high concentrations of LH increased GPER protein expression.…”