Effect Of Testosterone Deficiency Induced By Castration On Androgen Receptor And MtDNA Copy Number Of Pigs

Testosterone is the primary male sex hormone and plays an increasingly important role in mammalian development through its interaction with androgen receptor(AR).Mammalian mitochondrial biogenesis is a complex process involving mitochondrial proliferation and differentiation.Mitochondrial DNA transcription factor A(TFAM),which encodes a transcription factor that is essential for mitochondrial DNA(mtDNA)copy number and transcription,is regulated by peroxisome proliferator-activated receptor ? coactivator 1?(PGC1?).The function of AR in mitochondrial biogenesis induced by testosterone deficiency has not been investigated.Here we explored the molecular mechanism underlying the effect of testosterone deficiency on mitochondrial b androgen receptor iogenesis using a Yorkshire boar model by cell culture and biotreatment.The main results of this study are as follows:(1)Phenotypic data showed that body weight,body length,chest circumference,waist circumference and neck circumfere nce of castrated boars were significantly higher than those of control group(P < 0.01);Serum testosterone level of castrated group was significantly lower than that of control group(P < 0.01).Seminal vesicle gland,urethral bulb gland,prostate in the castrated group were significantly smaller than those in the control group(P < 0.01).These results showed that testosterone deficiency caused by castration led to reproductive system maldevelopment and indicated the successful establishment of a testosterone deficiency model in Yorkshire boars.(2)The qPCR results showed that the expression pattern of mtDNA copy number in the control group: muscle tissues > adipose tissues > endocrine glands > immune tissues,and the expression pattern of AR in the control group: endocrine glands > adipose tissues > immune tissues > muscle tissues.Testosterone deficiency caused by castration induced changes of mtDNA copy numbers in various tissues,and AR showed the opposite tendency to that of mtDNA copy number,particularly in adipose tissues and muscle tissues.We then analyzed the integrated optical density(IOD)and the results showed a high correlation between mitochondrial staining and qPCR results.(3)In addition,castration weakened the correlation of PGC1? and mtDNA copy number,but AR and TFAM showed a relatively high correlation in both control and castration pigs.Furthermore,luciferase assays revealed that AR binds to potential AR elements in the TFAM promoter to promote TFAM expression.In general,castration led to weight gain and reproductive system maldevelopment in pigs,and altered the tissue expression profile of mtDNA copy number and AR expression.The results showed that testosterone may be involved in the pathway linking PGC1? to mitochondrial biogenesis through AR interacting with TFAM.