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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Targeted disruption of ALK reveals a potential role in hypogonadotropic hypogonadism
PLoS ONE, Volume 10, No. 5, Article e0123542, Year 2015
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Description
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. Copyright © 2015 Witek et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Authors & Co-Authors
Witek, Barbara
Sweden, Umea
Umeå Universitet
El Wakil, Abeer
Sweden, Umea
Umeå Universitet
Helland, Åslaug
Norway, Oslo
Rikshospitalet-radiumhospitalet hf
Hallberg, Bengt
Sweden, Gothenburg
Göteborgs Universitet
Palmer, Ruth Helen
Sweden, Gothenburg
Göteborgs Universitet
Sweden, Umea
Umeå Universitet
Statistics
Citations: 24
Authors: 5
Affiliations: 3
Identifiers
Doi:
10.1371/journal.pone.0123542
ISSN:
19326203
Research Areas
Health System And Policy
Participants Gender
Male