Endocrine Abstracts

Spermatogenesis is a complex process involving interactions between the somatic cells (Sertoli, Leydig, peritubular) and germ cells within the adult testis. Androgens are key regulators of spermatogenesis and intra-testicular concentrations of testosterone (T), produced by the Leydig cells, are higher than that in blood. Androgen action is mediated by the androgen receptor (AR), an X-chromosome-encoded, ligand-activated, transcription factor. The mechanisms by which androgens regulate testis function have been explored by determining the pattern of expression of AR, by manipulating androgen concentrations, by performing studies in vitro on isolated tubules/cells and most recently by studying mice with cell-specific deletion of the Ar gene.

In adult testes AR have been immunolocalised to the nuclei of Sertoli, Leydig and peritubular myoid cells as well as the cells lining blood vessels. Expression in adult Sertoli cells is stage-dependent and in vitro studies have demonstrated that it is T-regulated. In rats, ablation of Leydig cells with ethane dimethane sulphonate results in an acute reduction in intra-testicular T and germ cell loss; germ cell demise is first observed in the stages of spermatogenesis in which AR expression in Sc is highest. The impact of Sertoli cell-specific ablation of Ar on testicular function has been investigated in three independent laboratories. In all cases Ar ablation resulted in a reduction in testicular size, germ cell loss and infertility. Expression of rHox5, a Sertoli cell protein previously shown to be T-regulated, was reduced as was expression of proteins involved in formation of junctional complexes. Leydig cell function was altered even though expression of Ar was maintained in these cells confirming the existence of paracrine interactions between the seminiferous and interstitial compartments. In conclusion, testicular function and male fertility are androgen dependent; expression of AR in Sertoli cells is essential for normal germ cell maturation and fertility.