Receptors and signaling pathways involved in proliferation and differentiation of Sertoli cells.

The identification of the hormones and other factors regulating Sertoli cell survival, proliferation, and maturation in neonatal, peripubertal, and pubertal life remains one of the most critical questions in testicular biology. The regulation of Sertoli cell proliferation and differentiation is thought to be controlled by cell-cell junctions and a set of circulating and local hormones and growth factors. In this review, we will focus on receptors and intracellular signaling pathways activated by androgen, follicle-stimulating hormone, thyroid hormone, activin, retinoids, insulin, insulin-like growth factor, relaxin, and estrogen, with special emphasis on estrogen receptors.

17β-estradiol signaling and regulation of Sertoli cell function.

In this review, we will present an overview of estrogen actions in the testis from immature and adult animals, with special emphasis on signaling mechanisms involved in the 17β-estradiol regulation of Sertoli cell function in immature rats. 17β-estradiol activates Sertoli cell proliferation in immature rats by a mechanism that involves the translocation of the estrogen receptors ESR1 and ESR2 to the plasma membrane, phosphorylation of epidermal growth factor receptor and activation of mitogen-activated protein kinase 3/1. Activation of the G protein-coupled estrogen receptor (GPER) also induces phosphorylation of mitogen-activated protein kinase 3/1 via epidermal growth factor receptor transactivation, which in turn increases expression of the antiapoptotic protein BCL2 and decreases the expression of proapoptotic protein BAX, indicating an antiapoptotic role of E2-GPER in immature rat Sertoli cells.