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Cited by 42Hypothalamic control of reproductive hormonesHormonal and reproductive studiesSperm and Testicular Function

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

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Luo, Jiao, Yang, Yan, Zhang, Tiantian, Su, Zhijian, Yu, Dan, Lin, Qilian, Chen, Haolin, Zhang, Qihao +4 more·2018·EBioMedicine
DOI 10.1016/j.ebiom.2018.08.021PMC PMC6161474
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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.

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  • Nerve growth factor has been shown to increase testosterone and LH levels in mice and is thought to promote pulsatile synthesis and release of GnRH.

    “Nerve growth factor has been shown to increase testosterone and LH levels in mice and is thought to promote the pulsatile synthesis and release of GnRH (76).”

    From Non-testosterone management of male hypogonadism: an examination of the existing literature (2020) · cites this paper as [76]

  • In senescent mice, intranasal delivery of nerve growth factor twice per week for 12 weeks resulted in increased levels of LH, FSH and testosterone, increased intratesticular testosterone, and increases in measures of sexual behavior.

    “Luo et al. recently demonstrated that intranasal delivery of nerve growth factor twice per week for 12 weeks in senescent mice resulted in increased levels of LH, FSH and testosterone, increased intratesticular testosterone, and increases in measures of sexual behavior in mice, including mounting and ejaculation times (76).”

    From Non-testosterone management of male hypogonadism: an examination of the existing literature (2020) · cites this paper as [76]

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Cited by

Sorted by citations

Authors
Luo, J., Yang, Y., Zhang, T., Su, Z., Yu, D., Lin, Q., Chen, H., Zhang, Q., Xiang, Q., Xue, W., Ge, R., & Huang, Y.
Affiliations
  • Jinan University (CN)
  • Wenzhou Medical University (CN)
Corresponding author
Huang, Yadong
ORCID
Venue
EBioMedicine
Publisher
Elsevier BV
Published
2018-09
Volume
35
Pages
295-306
ISSN
2352-3964 (ISSN-L)
DOI
10.1016/j.ebiom.2018.08.021
PMC
PMC6161474
OpenAlex
W2887181809
Cited by
42
References
7
Citations by year
2026: 3 · 2025: 4 · 2024: 6 · 2023: 8 · 2022: 6 · 2021: 5 · 2020: 8 · 2019: 1 · 2018: 1
FWCI
4.02
Type
journal article
Language
en
Open access
Licence
Locations
  • EBioMedicine (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (81730042, 81373313)
  • Natural Science Foundation of Guangdong Province (2015A030311010, 2015A030310132, 2018A030313473)
  • Wenzhou Municipal Science and Technology Bureau (8187060765, ZS2017009)
  • Guangzhou Municipal Science and Technology Project (201508020001, 2016A020214013)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
Keywords
nerve growth factor, age-related hypogonadism, hypogonadotropic hypogonadism, GnRH neurons, testosterone, intranasal drug delivery, hypothalamus, male fertility, semen quality, sexual function, SAMP8 mice, older men
MeSH terms
Administration, Intranasal, Aging, Animals, Female, Hypogonadism, Hypothalamus, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Male, Mice, Inbred BALB C, Neurons, Sexual Behavior, Animal, Spermatogenesis, Testosterone, Transcription, Genetic, Signal Transduction, Up-Regulation, Nerve Growth Factor

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