Endocrine Abstracts

In males androgens are primarily made by testicular Leydig cells and act as essential regulators of both fetal masculinization and adult reproductive function. The impact of androgens on gene transcription is largely mediated by the androgen receptor (AR), a member of the steroid hormone super-family of ligand activated transcription factors. AR is expressed widely throughout the body, including several key somatic cell-types in the testis. Although we have known for many years that androgens are important regulators of testicular development and function, until recently it has been impossible to determine the specific roles androgens play in each cell-type, and how these cells respond to androgens to ensure correct male development and fertility. We have exploited conditional gene-targeting of AR using the Cre/lox system to ablate AR function in several key cell-types of the testis, including the Sertoli cells (SC), peritubular myoid cells (PTM), vascular smooth muscle cells (VSM), vascular endothelial cells (VE), and Leydig cells (LC); with a view to elucidating the cell-specific roles of androgen-signalling within the testis. These studies have identified novel roles for each cell-type in the promotion of male reproductive function. AR-signalling in SCs controls post-meiotic germ cell development and LC number. AR-signalling in PTM cells controls all stages of GC development, SC function and LC differentiation. Whilst AR-signalling in VE cells appears dispensable for testicular function, AR-signalling in VSM cells controls testicular blood-flow and LC function. Recent unpublished data suggests AR-signalling in LCs is also important for testicular function, acting via a novel mechanism. Taken together, these studies provide increasing evidence for the presence of a complex androgen-dependent paracrine signalling pathway within the testis, with each AR-expressing cell-type influencing others to ensure their correct development and function.

Declaration of funding

This work was supported by the Medical Research Council (grant numbers MC_U127685841, G1100354) and Tenovus Scotland (grant number E08/6).