While HTPCs are not immune cells they produce IL

While HTPCs are not immune cells, they produce IL-6, MCP-1 and other immunologically relevant factors (Mayer et al., 2016). Our results demonstrated that epinephrine and phenylephrine increased the mRNA expression levels of COX-2, IL-6 and MCP-1 in HTPCs without affecting the mRNA expression level of IL-1β. No such effects were observed in the presence of salbutamol (the selective agonist of β2-ADR). Subsequent studies, using epinephrine or phenylephrine and a blocker of α1-ADRs (prazosin), confirmed that the production of inflammatory factors in HTPCs is regulated via α1-ADRs. These results were further confirmed by measurements of IL-6 and MCP-1 using a commercial available immunoassays and a cytokine profiler assay. The later revealed that other inflammatory factors were not markedly increased, with the exception of PTX 3, which was previously identified in HTPCs (Flenkenthaler et al., 2014, Mayer et al., 2016). The reported factors mainly act as pro-inflammatory agents. Inflammation of the human testis is of potential relevance to male infertility. In the testes of men suffering from idiopathic infertility due to impaired spermatogenesis, structural changes in the tubular wall of the seminiferous tubules can be often witnessed. A fibrotic thickening of the wall of the seminiferous tubules (Adam et al., 2012, Mayerhofer, 2013, Welter et al., 2013) and the high density of testicular immune sr9009 (macrophages and mast cells), present in such patients with idiopathic infertility, are clear signs of inflammation (Frungieri et al., 2002b, Meineke et al., 2000). The results obtained in our study suggest that via α1-ADRs, epinephrine can contribute to the inflammatory state in the testis. Sustained elevations of catecholamines occur during chronic stress. It is becoming clear that specifically chronic stress situations are linked to a number of human conditions, such as obesity and the metabolic syndrome, to alterations of the immune system, and interestingly, also to impaired testicular function (Furtado and Katzman, 2015, Hardy et al., 2005, Menacho-Marquez et al., 2013, Nargund, 2015, Qi and Ding, 2016). A recent study showed that chronic stress is negatively associated with semen quality in otherwise healthy men (Nordkap et al., 2016). Clearly, consequences of stress on reproductive functions may be due to a number of changes, including deranged hypothalamic-pituitary functions. Yet, our results in combination with previous studies in human testes and HTPCs (Mayer et al., 2016, Schell et al., 2008) may provide a partial explanation for this observation, since they link inflammation to male infertility. If this can be confirmed, the results may also lead to new treatment options. Several α1-ADRs inverse agonists and/or antagonists are already being used to treat nightmares associated with post-traumatic disorder and hypertension, or in combination to treat benign prostatic hyperplasia, as well as, disrupted sexual health, including erectile and ejaculatory dysfunctions (Cao et al., 2016, Hendrickson and Raskind, 2016, Seftel et al., 2007, Stojkov et al., 2013). The impact of α1-ADR antagonists on male (in)fertility and/or their future as potential therapeutic targets should therefore be further considered.
Study funding/competing interests The study was supported by grants from Deutsche Forschungsgemeinschaft (DFG; MA1080/23 and 25-1; to AM), Deutscher Akademischer Austauschdienst (DAAD; Short-Term Grant 57214227 and 57314022 to SR) and CONICET (to SR and MF).
Conflicts of interest
Acknowledgements
Introduction Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF family that functions as an endocrine hormone to regulate glucose and lipid metabolism [1]. FGF21 is primarily secreted by the liver as an endocrine hormone and is also expressed in multiple organs, including adipose tissue, thymus, skeletal muscle, and pancreas [1], [2]. Based on knowledge obtained mainly by studying transgenic mice overexpressing FGF21 [3] and administering recombinant FGF21 into animal models and humans [1], FGF21 is a promising target for the treatment of metabolic diseases [1].