Androgens are essential for life-long health and well-being[2]. Disruptions to the production or action of androgens are associated with many chronic pathologies, and metabolic disorders. Glucocorticoids, exerting their action via the glucocorticoid receptor (GR), can regulate androgen biosynthesis by blocking key enzymes required for their production in the androgen-producing cells in the testis, Leydig cells[3]. Despite glucocorticoid action on androgen production being well documented, how they regulate testis function is unknown.
To establish the role of GR-signalling in the testis in adulthood, we utilised a novel technique to rapidly generate cell specific knockouts using adeno-associated virus to deliver Cre recombinase to Leydig cells specifically. Leydig cell GR knockout mice were generated via injection of Adeno-Associated Virus serous type-9 (AAV-9)[4] carrying either GFP (control) or Cre recombinase into the interstitial compartment of the testis of GR floxed mice. Mice were injected in adulthood and were collected following one round of spermatogenesis.
Our preliminary data demonstrate that blockade of GR signalling in Leydig cells shows markedly suppressed luteinizing hormone receptor (Lhcgr) and steroidogenic enzymes required for normal androgen production. Furthermore, an increase in DHT in these mice demonstrates that Leydig cells are in a compensatory state following GR ablation. This important new data suggests that GR-signalling plays a physiological role in normal testis function and potentially fertility. These novel findings provide a timely and previously unavailable opportunity to elucidate the role of GR-signalling in testis function and its ability to influence LC function and androgen production.