Role of GPER-Mediated Signaling in Testicular Functions and Tumorigenesis

Abstract

Estrogen signaling plays important roles in testicular functions and tumorigenesis. Fifteen years ago, it was discovered that a member of the G protein-coupled receptor family, GPR30, which binds also with high affinity to estradiol and is responsible, in part, for the rapid non-genomic actions of estrogens. GPR30, renamed as GPER, was detected in several tissues including germ cells (spermatogonia, spermatocytes, spermatids) and somatic cells (Sertoli and Leydig cells). In our previous review published in 2014, we summarized studies that evidenced a role of GPER signaling in mediating estrogen action during spermatogenesis and testis development. In addition, we evidenced that GPER seems to be involved in modulating estrogen-dependent testicular cancer cell growth; however, the effects on cell survival and proliferation depend on specific cell type. In this review, we update the knowledge obtained in the last years on GPER roles in regulating physiological functions of testicular cells and its involvement in neoplastic transformation of both germ and somatic cells. In particular, we will focus our attention on crosstalk among GPER signaling, classical estrogen receptors and other nuclear receptors involved in testis physiology regulation.

Keywords: GPER; Leydig cells; Sertoli cells; germ cells; telocytes; testicular cancer; testis; testis physiology.

Figure 1

GPER role in testicular interstitial and tubular compartment and in epididymis. In this figure are summarized the knowledge of GPER role (B) in testicular interstitial and tubular compartments (A) and in epididymis. The drawing represents a cross section of seminiferous tubules, surrounding interstitium and several testicular cell types (A). LC: Leydig cells; TC: telocytes; SC: Sertoli cells; PT: peritubular cells; SPG: spermatogonia; SPT: spermatocytes; RS: round spermatids; SPZ: spermatozoa.

Figure 2

GPER role in testicular tumorigenesis. In this figure are summarized the knowledge ofGPER role in seminomas and Leydig cell tumors [LCTs]. LC: Leydig cells; TC: telocytes; SC: Sertoli cells; PT: peritubular cells; GON: gonocytes; SPG: spermatogonia; SPT: spermatocytes; RS: round spermatids; SPZ: spermatozoa.