Abstract
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.
Full text
PDF
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ben-Jonathan N., Peleg E., Hoefer M. T. Optimization of culture conditions for short-term pituitary cell culture. Methods Enzymol. 1983;103:249–257. doi: 10.1016/s0076-6879(83)03016-5. [DOI] [PubMed] [Google Scholar]
- DeFranco D., Schmidt O., Söll D. Two control regions for eukaryotic tRNA gene transcription. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3365–3368. doi: 10.1073/pnas.77.6.3365. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hanahan D. Transgenic mice as probes into complex systems. Science. 1989 Dec 8;246(4935):1265–1275. doi: 10.1126/science.2686032. [DOI] [PubMed] [Google Scholar]
- Mahon K. A., Chepelinsky A. B., Khillan J. S., Overbeek P. A., Piatigorsky J., Westphal H. Oncogenesis of the lens in transgenic mice. Science. 1987 Mar 27;235(4796):1622–1628. doi: 10.1126/science.3029873. [DOI] [PubMed] [Google Scholar]
- Mason A. J., Hayflick J. S., Zoeller R. T., Young W. S., 3rd, Phillips H. S., Nikolics K., Seeburg P. H. A deletion truncating the gonadotropin-releasing hormone gene is responsible for hypogonadism in the hpg mouse. Science. 1986 Dec 12;234(4782):1366–1371. doi: 10.1126/science.3024317. [DOI] [PubMed] [Google Scholar]
- Mellon P. L., Windle J. J., Goldsmith P. C., Padula C. A., Roberts J. L., Weiner R. I. Immortalization of hypothalamic GnRH neurons by genetically targeted tumorigenesis. Neuron. 1990 Jul;5(1):1–10. doi: 10.1016/0896-6273(90)90028-e. [DOI] [PubMed] [Google Scholar]
- Radovick S., Wondisford F. E., Nakayama Y., Yamada M., Cutler G. B., Jr, Weintraub B. D. Isolation and characterization of the human gonadotropin-releasing hormone gene in the hypothalamus and placenta. Mol Endocrinol. 1990 Mar;4(3):476–480. doi: 10.1210/mend-4-3-476. [DOI] [PubMed] [Google Scholar]
- Schwanzel-Fukuda M., Pfaff D. W. Origin of luteinizing hormone-releasing hormone neurons. Nature. 1989 Mar 9;338(6211):161–164. doi: 10.1038/338161a0. [DOI] [PubMed] [Google Scholar]
- Seeburg P. H., Mason A. J., Stewart T. A., Nikolics K. The mammalian GnRH gene and its pivotal role in reproduction. Recent Prog Horm Res. 1987;43:69–98. doi: 10.1016/b978-0-12-571143-2.50008-3. [DOI] [PubMed] [Google Scholar]
- Wray S., Grant P., Gainer H. Evidence that cells expressing luteinizing hormone-releasing hormone mRNA in the mouse are derived from progenitor cells in the olfactory placode. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8132–8136. doi: 10.1073/pnas.86.20.8132. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wray S., Nieburgs A., Elkabes S. Spatiotemporal cell expression of luteinizing hormone-releasing hormone in the prenatal mouse: evidence for an embryonic origin in the olfactory placode. Brain Res Dev Brain Res. 1989 Apr 1;46(2):309–318. doi: 10.1016/0165-3806(89)90295-2. [DOI] [PubMed] [Google Scholar]