ABSTRACT
Testosterone is critical for spermatogenesis and male fertility. Testosterone primarily mediates its actions through the androgen receptor (AR). It is well known that in the absence of testosterone and/or the androgen receptor, spermatogenesis cannot progress. Classical testosterone signaling can directly incur gene expression, while the nonclassical pathway involves the activation of certain kinases that mediate the action. The AR is located on the Sertoli cells, but germ cells lack this. Signaling by testosterone initiates in the Sertoli cells and acts on germ cells by way of estrogens secreted by the germ cells. These estrogens act on the estrogen receptors (ERs), ERα, ERβ and G-protein-coupled estrogen receptor (GPER). While testosterone binding to the AR and subsequent regulation of the gene expression response has been shown to saturate at concentrations of 1 nM only, a very high level of testicular testosterone (>70 nM) is essential to maintain spermatogenesis in rodents. Despite a well-defined need for testosterone in spermatogenesis, the mechanisms by which testosterone signaling regulates the intricate fine-tuning of spermatogenic processes are not well defined. In this chapter, we highlighted the newer aspects of testosterone signaling that extend its classical endocrine regulatory role, especially emphasizing its mechanism of action in target organs and in-depth signaling cascades.
