Angiotensin II regulates testicular peritubular cell function via AT1 receptor: a specific situation in male infertility.

We observed that peritubular myoid cells in the human testis are immunoreactive for angiotensin II (AngII) receptors (AT1R) and explored AngII actions in cultured human testicular peritubular cells (HTPCs). In response to AngII they contracted within minutes. The AT1R-blocker losartan blocked contraction, implying involvement of AngII and AT1R in intratesticular sperm transport. AngII also significantly increased IL-6 mRNA levels and IL-6 secretion within hours and losartan again prevented this action. This suggests involvement in inflammatory processes, which may play a role in male infertility. AngII can be generated locally by mast cell (MC)-derived chymase (CHY), which cleaves AngI. In testicular biopsies from infertile men we found abundant MCs, which express CHY, within the wall of seminiferous tubules. In contrast, CHY-positive MCs are hardly found in normal human testis. Testicular inflammatory events may fuel processes resulting in impaired spermatogenesis. Therefore therapeutic interference with MCs, CHY or AT1R might be novel options in male infertility.