Migratory Arrest of Gonadotropin-Releasing Hormone Neurons in Transgenic Mice

Gonadotropin-releasing hormone (GnRH) is important in reproduction, although the mechanism of central hypogonadism in humans remains unclear. Because the GnRH neuron originates from the olfactory placode and migrates to the hypothalamus during development, central hypogonadism in humans could be cau...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1991-04, Vol.88 (8), p.3402-3406
Main Authors: Radovick, Sally, Wray, Susan, Lee, Eric, Nicols, Donald K., Nakayama, Yuko, Weintraub, Bruce D., Westphal, Heiner, Cutler, Gordon B., Wondisford, Frederic E.
Format: Article
Language:English
Subjects:
Animals
antigen T
Antigens, Polyomavirus Transforming - genetics
Antigens, Polyomavirus Transforming - metabolism
Biological and medical sciences
Cell Movement
Endocrinopathies
Female
Gene Expression
Gonadotropin-Releasing Hormone - genetics
Gonadotropin-Releasing Hormone - metabolism
Humans
Hypogonadism
Hypogonadism - genetics
Hypogonadism - pathology
Hypothalamus
Hypothalamus - cytology
Hypothalamus. Hypophysis. Epiphysis (diseases)
Infertility, Female
Infertility, Male
Male
Male animals
Mating behavior
Medical sciences
Mice
Mice, Transgenic
migration
Neurons
Neurophysins - metabolism
Promoter Regions, Genetic
Recombinant Proteins
SV40
Transgenic animals
Tumors
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Summary:Gonadotropin-releasing hormone (GnRH) is important in reproduction, although the mechanism of central hypogonadism in humans remains unclear. Because the GnRH neuron originates from the olfactory placode and migrates to the hypothalamus during development, central hypogonadism in humans could be caused by failure in normal migration of GnRH neurons to the hypothalamus. We report that in transgenic mice expression of the simian virus 40 T antigen, driven by the promoter of human GnRH gene, resulted in central hypogonadism due to an arrest in neuronal migration during development and tumor formation along the migratory pathway. This system appears to be an important animal model of hypogonadotropic hypogonadism in humans. Additionally, olfactory bulb tumors from these animals were dispersed, and a GnRH-secreting neuronal cell line (GN cell line) was established.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.88.8.3402