Therapeutic Effect Of Nerve Growth Factor On Late-onset Hypogonadism In SAMP8 Mice And Its Mechanism

Nerve growth factor(NGF)plays essential roles in regulating the development and maintenance of central sympathetic and sensory neurons.However,the effects of NGF on hypogonadism remain unexplored.Here,we report a significant function of NGF in inducing gonadotropin-releasing hormone(Gn RH)production and endogenous testosterone secretion by the activation of tyrosine receptor kinase A(Trk A)signaling,which can robustly enhance sexual function,improve sperm quality,and restore the fertility of aging SAMP8(the senescence accelerate mouse P8)male mice with lateonset hypogonadism(LOH).We also established an effective and convenient way to deliver NGF to the hypothalamus: spraying liposome-encapsulated NGF into the nasal cavity.NGF treatment can also alleviate various age-related symptoms and improve the movement of the individual.We conclude that NGF could rescue fertility through direct interaction with Gn RH neurons in hypothalamus and normalize hormone levels of luteinizing hormone(LH)and testosterone through the hypothalamic-pituitary-testis(HPT)axis,and may even be a treatment for hypogonadotrophic hypogonadism and its related subfertility.