Activation of PTH1R alleviates epididymitis and orchitis through Gq and β-arrestin-1 pathways
Ming-Wei Wang, Zhao Yang, Xu Chen, Shuhua Zhou, Gelin Huang, Jian-Ning Sun, Hui Jiang, Wenming Xu, Haocheng Lin, Xiao Yu, Jin‐Peng Sun
Abstract
Significance Currently, male infertility has become a public health issue. The inflammations in the epididymis and testis are estimated to account for 6 to 15% of male infertility and thus have attracted increasing attention. Conventional therapies for epididymitis and orchitis using antibiotics have limitations in terms of side effects and ineffectiveness for nonbacterial inflammations, thus highlighting an urgent need for novel therapeutic strategies. Here, the screening of secretin family G protein–coupled receptors (GPCRs) enabled us to identify that activation of PTH1R by a Food and Drug Administration–approved osteoporosis drug abaloparatide effectively counteracts epididymitis and orchitis through selective transducer-mediated pathways. Our results offer potential therapeutics to treat epididymitis and orchitis by targeting GPCRs other than traditional antibiotic therapies.