Nasal delivery of nerve growth factor rescue hypogonadism by up-regulating GnRH and testosterone in aging male mice

Jiao Luo, Yan Yang, Tiantian Zhang, Zhijian Su, Dan Yu, Qilian Lin, Haolin Chen, Qihao Zhang, Qi Xiang, Wei Xue, Renshan Ge, Yadong Huang

Research output: Contribution to journalArticle

Abstract

Background: 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. Methods: To assess the effects of NGF on hypogonadism, we established a convenient and noninvasive way to deliver NGF to the hypothalamus by spraying liposome-encapsulated NGF into the nasal cavity. The ten-month-old aging male senescence accelerate mouse P8 (SAMP8) mice with age-related hypogonadotrophic hypogonadism were used to study the role of NGF in hypogonadism. The age-matched accelerated senescence-resistant mouse R1 (SAMR1) served as a control. The ten-month-old SAMP8 mice were treated with NGF twice per week for 12 weeks. Sexual hormones, sexual behaviors, and fertility were analyzed after NGF treatment. And the mechanisms of NGF in sex hormones sexual function were also studied. Findings: NGF could enhance the sexual function, improve the quality of the sperm, and restore the fertility of aging male SAMP8 mice with age-related hypogonadism by activating gonadotropin-releasing hormone (GnRH) neuron and regulating secretion of GnRH. And NGF regulated the GnRH release through the PKC/p-ERK1/2/p-CREB signal pathway. Interpretation: These results suggest that NGF treatment could alleviate various age-related hypogonadism symptoms in male SAMP8 and may be usefulness for age-related hypogonadotrophic hypogonadism and its related subfertility. Fund: National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, the Science and Technology Plan Project of Guangzhou, Wenzhou Science & Technology Bureau, Guangdong Province Pearl River Scholar Fund, Guangdong province science and technology innovation leading Scholar Fund.

Original languageEnglish (US)
JournalEBioMedicine
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

Hypogonadism
Nerve Growth Factor
Nose
Gonadotropin-Releasing Hormone
Testosterone
Aging of materials
Natural Science Disciplines
Natural sciences
Technology
Neurons
Fertility
Nasal Cavity
Gonadal Steroid Hormones
Sensory Receptor Cells
Spraying
Rivers
Liposomes
Sexual Behavior
Infertility
Hypothalamus

Keywords

  • Fertility
  • GnRH
  • Hypogonadism
  • NGF
  • Testosterone

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Nasal delivery of nerve growth factor rescue hypogonadism by up-regulating GnRH and testosterone in aging male mice. / Luo, Jiao; Yang, Yan; Zhang, Tiantian; Su, Zhijian; Yu, Dan; Lin, Qilian; Chen, Haolin; Zhang, Qihao; Xiang, Qi; Xue, Wei; Ge, Renshan; Huang, Yadong.

In: EBioMedicine, 01.01.2018.

Research output: Contribution to journalArticle

Luo, Jiao ; Yang, Yan ; Zhang, Tiantian ; Su, Zhijian ; Yu, Dan ; Lin, Qilian ; Chen, Haolin ; Zhang, Qihao ; Xiang, Qi ; Xue, Wei ; Ge, Renshan ; Huang, Yadong. / Nasal delivery of nerve growth factor rescue hypogonadism by up-regulating GnRH and testosterone in aging male mice. In: EBioMedicine. 2018.
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AU - Luo, Jiao

AU - Yang, Yan

AU - Zhang, Tiantian

AU - Su, Zhijian

AU - Yu, Dan

AU - Lin, Qilian

AU - Chen, Haolin

AU - Zhang, Qihao

AU - Xiang, Qi

AU - Xue, Wei

AU - Ge, Renshan

AU - Huang, Yadong

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: 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. Methods: To assess the effects of NGF on hypogonadism, we established a convenient and noninvasive way to deliver NGF to the hypothalamus by spraying liposome-encapsulated NGF into the nasal cavity. The ten-month-old aging male senescence accelerate mouse P8 (SAMP8) mice with age-related hypogonadotrophic hypogonadism were used to study the role of NGF in hypogonadism. The age-matched accelerated senescence-resistant mouse R1 (SAMR1) served as a control. The ten-month-old SAMP8 mice were treated with NGF twice per week for 12 weeks. Sexual hormones, sexual behaviors, and fertility were analyzed after NGF treatment. And the mechanisms of NGF in sex hormones sexual function were also studied. Findings: NGF could enhance the sexual function, improve the quality of the sperm, and restore the fertility of aging male SAMP8 mice with age-related hypogonadism by activating gonadotropin-releasing hormone (GnRH) neuron and regulating secretion of GnRH. And NGF regulated the GnRH release through the PKC/p-ERK1/2/p-CREB signal pathway. Interpretation: These results suggest that NGF treatment could alleviate various age-related hypogonadism symptoms in male SAMP8 and may be usefulness for age-related hypogonadotrophic hypogonadism and its related subfertility. Fund: National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, the Science and Technology Plan Project of Guangzhou, Wenzhou Science & Technology Bureau, Guangdong Province Pearl River Scholar Fund, Guangdong province science and technology innovation leading Scholar Fund.

AB - Background: 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. Methods: To assess the effects of NGF on hypogonadism, we established a convenient and noninvasive way to deliver NGF to the hypothalamus by spraying liposome-encapsulated NGF into the nasal cavity. The ten-month-old aging male senescence accelerate mouse P8 (SAMP8) mice with age-related hypogonadotrophic hypogonadism were used to study the role of NGF in hypogonadism. The age-matched accelerated senescence-resistant mouse R1 (SAMR1) served as a control. The ten-month-old SAMP8 mice were treated with NGF twice per week for 12 weeks. Sexual hormones, sexual behaviors, and fertility were analyzed after NGF treatment. And the mechanisms of NGF in sex hormones sexual function were also studied. Findings: NGF could enhance the sexual function, improve the quality of the sperm, and restore the fertility of aging male SAMP8 mice with age-related hypogonadism by activating gonadotropin-releasing hormone (GnRH) neuron and regulating secretion of GnRH. And NGF regulated the GnRH release through the PKC/p-ERK1/2/p-CREB signal pathway. Interpretation: These results suggest that NGF treatment could alleviate various age-related hypogonadism symptoms in male SAMP8 and may be usefulness for age-related hypogonadotrophic hypogonadism and its related subfertility. Fund: National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, the Science and Technology Plan Project of Guangzhou, Wenzhou Science & Technology Bureau, Guangdong Province Pearl River Scholar Fund, Guangdong province science and technology innovation leading Scholar Fund.

KW - Fertility

KW - GnRH

KW - Hypogonadism

KW - NGF

KW - Testosterone

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