Parathyroid Hormone-Related Protein Promotes Rat Stem Leydig Cell Differentiation

• Main Authors: Tiantian Song, Yiyan Wang, Huitao Li, Lanlan Chen, Jianpeng Liu, Xianwu Chen, Xiaojun Li, Xiaoheng Li, Linxi Li, Qingquan Lian, Ren-Shan Ge
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2017-11-01
• Series: Frontiers in Physiology
• Subjects: Leydig cell; stem Leydig cell; PTHrP; differentiation; testosterone
• Online Access: http://journal.frontiersin.org/article/10.3389/fphys.2017.00911/full

The regulatory factors for stem Leydig cell development are largely unknown. Herein, we reported that parathyroid hormone-related protein (PTHrP) may be a factor to regulate this process. The effects of PTHrP on rat stem Leydig cell proliferation and differentiation were investigated using a stem Leydig cell culture system and an ethane dimethane sulfonate (EDS)-treated in vivo Leydig cell regeneration model. PTHrP (1,000 pg/ml) significantly increased medium testosterone level and up-regulated STAR, CYP17A1, and 17β-HSD3 expressions. Co-treatment with PKA inhibitor H-89 or PKC inhibitor U73122 reversed PTHrP-mediated increase of testosterone production in vitro. Intratesticular injection of PTHrP (100 ng/testis) into the Leydig cell-depleted testis from post-EDS day 7 to 21 significantly increased serum testosterone level, up-regulated LHCGR, SCARB1, CYP11A1, 11β-HSD1, and CYP17A1 expressions. It also enlarged Leydig cell size without affecting PCNA-labeled Leydig cell number. This indicates that PTHrP promotes stem Leydig cell differentiation. PTHrP in vivo increased CREB and p-CREB levels, suggesting that PTHrP acts via a PKA-CREB signaling pathway. In conclusion, PTHrP stimulates stem Leydig cell differentiation without affecting its proliferation, showing its novel action and mechanism on rat stem Leydig cell development.