Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism
| العنوان: | Targeted Disruption of ALK Reveals a Potential Role in Hypogonadotropic Hypogonadism |
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| المؤلفون: | Oleg A. Alexeyev, Åslaug Helland, Abeer El Wakil, Barbara Witek, Emma Vernersson-Lindahl, Bengt Hallberg, Ruth H. Palmer, Christoffer Nord, Ulf Ahlgren, Maria Eriksson |
| المصدر: | PLoS ONE, Vol 10, Iss 5, p e0123542 (2015) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, lcsh:Medicine, Gonadotropin-releasing hormone, Biology, Gonadotropin-Releasing Hormone, Gene Knockout Techniques, Hypogonadotropic hypogonadism, Internal medicine, hemic and lymphatic diseases, medicine, Anaplastic lymphoma kinase, Animals, Anaplastic Lymphoma Kinase, Testosterone, lcsh:Science, Mice, Knockout, Cancer och onkologi, Multidisciplinary, Crizotinib, Sperm Count, GATA4, Hypogonadism, lcsh:R, Wild type, Receptor Protein-Tyrosine Kinases, medicine.disease, Spermatozoa, Mice, Inbred C57BL, Endocrinology, Hypothalamus, Cancer and Oncology, lcsh:Q, medicine.drug, Research Article |
| الوصف: | Mice lacking ALK activity have previously been reported to exhibit subtle behavioral phenotypes. In this study of ALK of loss of function mice we present data supporting a role for ALK in hypogonadotropic hypogonadism in male mice. We observed lower level of serum testosterone at P40 in ALK knock-out males, accompanied by mild disorganization of seminiferous tubules exhibiting decreased numbers of GATA4 expressing cells. These observations highlight a role for ALK in testis function and are further supported by experiments in which chemical inhibition of ALK activity with the ALK TKI crizotinib was employed. Oral administration of crizotinib resulted in a decrease of serum testosterone levels in adult wild type male mice, which reverted to normal levels after cessation of treatment. Analysis of GnRH expression in neurons of the hypothalamus revealed a significant decrease in the number of GnRH positive neurons in ALK knock-out mice at P40 when compared with control littermates. Thus, ALK appears to be involved in hypogonadotropic hypogonadism by regulating the timing of pubertal onset and testis function at the upper levels of the hypothalamic-pituitary gonadal axis. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3c51302c563212d86bdb0487fe1e36da http://europepmc.org/articles/PMC4425494?pdf=render |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3c51302c563212d86bdb0487fe1e36da |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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