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.
Highlights
The mammalian testis is divided into two compartments, the seminiferous tubules including germ cells in various development stages supported by Sertoli cells and the interstitial tissue consisting of loose connective tissue, blood and lymphatic vessels, Leydig cells, fibroblasts, macrophages, leukocytes, and telocytes [1,2].Testis physiological function consists of spermatogenesis, a process leading to gametes formation occuring in seminiferous tubules regulated by autocrine/paracrine factors, and steroidogenesis that occurs in Leydig cells [3]
We will focus our attention on crosstalk among GPER signaling, classical estrogen receptors and other nuclear receptors involved in the testis physiology regulation
GPER inhibition caused an increase in telocytes number, ERRs mRNA expression and mouse testis relaxin concentration, a protein exclusively secreted by Leydig cells
Summary
The mammalian testis is divided into two compartments, the seminiferous tubules including germ cells in various development stages (spermatogonia, spermatocytes, spermatids, spermatozoa) supported by Sertoli cells and the interstitial tissue consisting of loose connective tissue, blood and lymphatic vessels, Leydig cells, fibroblasts, macrophages, leukocytes, and telocytes [1,2]. Cellular response to estrogens is mediated through interaction with nuclear ERs α and β, which activates genomic and non-genomic signaling [6,7,8,9,10,11]. It has been well established that GPER is expressed in testicular cells where it regulates specific functions [30,31,32,33], but it can be involved in pathological processes, such as cancer [27,34], including estrogen-dependent testicular tumors [35]. The generation of a triple KO [ESRs and GPER] would be useful to highlight the cross-talk and functional redundancy between the three different receptors as well as between genomic and non-genomic effects exerted by estrogens in the modulation of spermatogenesis and testicular tumorigenesis [35]. We will focus our attention on crosstalk among GPER signaling, classical estrogen receptors and other nuclear receptors involved in the testis physiology regulation
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