Male infertility, due to impaired spermatogenesis, is accompanied typically by fibrotic remodeling of the testicular peritubular wall and accumulation of tryptase-positive mast cells (MCs). Fibrotic remodeling, as we found, also includes deposits of an extracellular matrix (ECM) protein, namely the proteoglycan decorin (DCN), which is produced by peritubular cells. Importantly, DCN can interact with several growth factor receptors (GFRs). Hence we explored aspects of its possible role in the human testis using a relevant cellular model, human testicular peritubular cells. These cells stem from men with normal spermatogenesis (HTPCs), and from men with impaired spermatogenesis and existing fibrosis (HTPC-Fs). HTPC-Fs produced and secreted more DCN than HTPCs and in contrast to HTPCs, responded to mast cell tryptase and a tryptase receptor (PAR-2) agonist by further increased production and secretion of DCN. That DCN can interact with GFRs expressed by these cells was shown by its ability to rapidly phosphorylate GFRs, including epidermal GFRs (EGFRs) and platelet-derived GFRs (PDGFRs), and to acutely increase intracellular Ca²⁺ levels. While DCN was not able to affect proliferation of HTPC/HTPC-Fs alone, it blocked the actions of EGF and PDGF, which act as mitogens and in HTPC/HTPC-Fs. Thus the ECM component DCN acts as a ligand for several testicular GFRs expressed by peritubular cells of the human testis. Increased amounts of DCN found in male infertility may be a consequence of actions of MC-derived tryptase. This may result in general or focal deposits of DCN, which consequently may imbalance paracrine signaling pathways in the human testis. DFG MA 1080/16-3; DAAD, Academy of Finland.