Identification of the estrogen receptor GPER in neoplastic and non-neoplastic human testes

Abstract

BackgroundEstrogen signaling is mediated by estrogen receptor beta isoforms in normal and neoplastic human testes. Recently, a G-protein-coupled-receptor (GPER) has been suggested as being involved in rapid responses to estrogens in different normal and tumor cells.MethodsThis study investigated the GPER expression in paraffin-embedded samples from non neoplastic and neoplastic human testes (sex-cord stromal and germ cell tumors) by immunohistochemical and Western Blot analyses.ResultsIn control testes, a positive GPER immunoreactivity was detected in Leydig and in Sertoli cells while all germ cells were immunonegative. Furthermore, neoplastic cells of the Sertoli cell tumor, Leydig cell tumor, seminoma and embryonal carcinoma samples were all immunopositive. The immunoblots of testis extracts confirmed the results.ConclusionsThese findings suggest that GPER could mediate estrogen signaling in both normal and transformed somatic cells of human testis, but they reveal a differential expression of the novel estrogen receptor in non neoplastic and neoplastic germ cells.

17β-estradiol signaling and regulation of Sertoli cell function

“…Furthermore, neoplastic cells of the Sertoli cell tumor, Leydig cell tumor, seminoma and embryonary carcinoma are all immunopositive. 64 Analysis of GPER expression in several types of post-pubertal testicular germ cell tumors confirmed high level of GPER expression in all intratubular germ cell tumors, seminomas and embryonic carcinomas, but low level in teratomas. 65 In conclusion, ESRs and GPER can mediate the rapid E2 actions in Sertoli cells, which in turn can modulate nuclear Figure 2.…”

Estrogenic regulation of bicarbonate transporters from SLC4 family in rat Sertoli cells

“…Indeed, the strikingly higher expression of AE2 in SCs seems not in agreement with the effect of E2 on the ATP-generated I sc . In these cells, I sc stimulation is due to ATP-activated Cl -channels, which move negative charges from the intracellular milieu towards the apical compartment [11]. The resultant decrease of intracellular content of Cl -will activate AE2 in order to replenish the cell and allow a continuous ''leakage'' of Cl -through its specific ATP-activated apical channels.…”

“…Expression of E2 receptors, namely ERa and ERb in testis has been described in human testicular biopsies with distinct spermatogenic phenotypes [10]. In the human testis, it was shown that ERa, ERb, and GPR30 are expressed in neoplastic and non-neoplastic testicular tissue [11], SCs, and diploid germ cells [7]. SCs are responsible for establishing the luminal microenvironment by controlling the movement of substances from the interstitial fluid to the STF.…”

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

“…All of them are known to be expressed in the human testis and are physiologically activated by estradiol (E2). The two nuclear estrogen receptors (ESR1 and ESR2) act primarily as transcription factors (Hess et al , 2011; reviewed in Heldring et al ., 2007; Stanisic et al ., 2010), whereas the more recently discovered membrane-associated G protein-coupled estrogen receptor (GPER or formerly known as GPR-30) mediates predominantly rapid non-genomic effects (Rago et al ., 2011; Hess et al ., 2011). Nevertheless each of the three estrogen receptors is able to mediate rapid signaling events and induce changes in gene transcription (Prossnitz et al ., 2008).…”

“…In normal adult human and rat testes, GPER was reported in somatic (Sertoli and Leydig cells; Lucas et al ., 2010; Rago et al ., 2011) and germ cells (spermatogonia and spermatocytes; Chevalier et al , 2012). It was also described in germ cell tumors (Franco et al ., 2011) and in rat tumor Leydig cells (R2C) (Chimento et al , 2013).…”