Endocrine regulation of the testis. Pituitary gonadotropins are the chief regulators of testicular function; FSH acts through its receptors in Sertoli cells (FSHR) to regulate spermatogenesis and LH stimulates androgen production by Leydig cells after binding to LHR. However, gonadal steroids, i.e., androgen and estrogen, and other agents that bind or prevent binding to steroid hormone receptors (androgen receptor AR, ERα, and ERβ), which are present in Sertoli cells, germ cells and Leydig cells also regulate testicular function. The pathway mediated by adenosine-3',5'-cyclic monophosphate (cAMP) appears to be the primary intracellular signaling pathway in all testicular cells. However, several growth factors e.g., insulin like growth factor-1 (IGF-1) and epidermal growth factor (EGF), acting via their receptors, IGF-1R and EGF-R, possibly modulate AR and ER-mediated pathways. Thus, testicular function is regulated by interactions between several signaling pathways, some acting locally, e.g., AR and ER-mediated pathways, and others indirectly by modulating hypothalamus-pituitary function. Hormonal activation of transcriptional gene activity results in changes in cell differentiation and function. PMC, peritubular myoid cell; CRE, cAMP-responsive elements, ARE, androgen-responsive elements; ERE, estrogen-responsive elements.