Leydig cells tumors (LCTs) represent the most frequent interstitial neoplasm of the testis, however their etiology is still unknown. Leydig cells (LCs) are essential players of spermatogenesis and drive the expression of male secondary sexual characteristics. cAMP/PKA signaling pathway has been demonstrated to be the mast regulator of androgen production in LCs. cAMP levels in male gonads are finely regulated by Phosphodiesterase 8 (PDE8) family. The PDE8 family consists of two distinct genes, Pde8a and Pde8b. Both PDE8A and PDE8B are able to hydrolyze cAMP with a very high affinity and have been demonstrated to be highly expressed in LCs. Even if PDE8 is considered a key regulator of steroidogenesis its role in LCs transformation has not been clarified. The aim of this proposal is to evaluate if PDE8 could represent a valuable marker of Leydig cell tumors.
Given the multiple roles played by PDE8 in steroidogenesis and LCs physiology, it is reasonable to hypnotize a role of PDE8 in the pathogenesis of LC tumors. The understanding of cAMP molecular pathway and their effectors in Leydig cells will potentially lead to the identification of molecular markers of LCs dysfunction.
In particular, if PDE8A and/or PDE8B will result upregulated in LCTs, they could become novel diagnostic markers with clinical implications in the development of diagnosis and therapeutic strategies to prevent LC dysfunction.