Oncostatin M stimulates immature Leydig cell proliferation but inhibits its maturation and function in rats through JAK1/STAT3 signaling and induction of oxidative stress in vitro.

BACKGROUND:Oncostatin M (OSM) is a member of the interleukin-6 group of cytokines, which can regulate cell proliferation, growth, and function. Immature Leydig cells have the ability to proliferate and differentiate, and adult Leydig cells have the function of testosterone synthesis. However, the role and underlying mechanisms of OSM on the proliferation and function of Leydig cells remain unclear. METHODS:The effects of OSM on the proliferation, apoptosis, and function of immature Leydig cells isolated from 35-day-old rats and the function of adult Leydig cells isolated from 63-day-old rats in vitro. RESULTS:OSM stimulated immature Leydig cell proliferation after up-regulating the expression of Ccnd1 and Cdk4 to drive the transition of G1 phase to M2 phase in the cell cycle at 10 and 100 ng/ml. OSM did not affect the apoptosis of immature Leydig cells up to 100 ng/ml. OSM inhibited testosterone production in immature and adult Leydig cells by down-regulating the expression of Lhcgr, Star, Cyp11a1, Hsd3b1, and Cyp17a1 at 1-100 ng/ml. OSM induced reactive oxygen species and down-regulated the expression of antioxidant genes and lowered mitochondrial membrane potential at 10 and 100 ng/ml in both Leydig cells. Janus kinase 1 (JAK1) antagonist filgotinib and signal transducer and activator of transcription 3 (STAT3) antagonist S3I-201 reversed the effect of OSM, indicating that it acts on JAK1/STAT3 signaling. CONCLUSION:Oncostatin M stimulates immature Leydig cell proliferation while inhibiting the function of immature and adult Leydig cells.