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Prolactin Signalling in the Mouse Hypothalamus is Primarily Mediated by Signal Transducer and Activator of Transcription Factor 5b but not 5a
Author(s) -
Yip S. H.,
Eguchi R.,
Grattan D. R.,
Bunn S. J.
Publication year - 2012
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.2012.02357.x
Subject(s) - prolactin , stat5 , medicine , endocrinology , hypothalamus , prolactin receptor , biology , stat protein , gene isoform , activator (genetics) , prolactin cell , phosphorylation , receptor , hormone , stat3 , microbiology and biotechnology , gene , biochemistry
Prolactin acts at multiple targets throughout the body, including the mammary gland, heart, liver, muscle and brain. Upon binding to its receptors, prolactin signals through the phosphorylation and thus activation of signal transducer and activator of transcription 5 ( STAT 5). There are two very similar STAT 5 isoforms, termed STAT 5a and STAT 5b, which are selectively activated by prolactin in specific tissues. Various brain regions, including the hypothalamus, are prolactin responsive, although the STAT 5 isoform involved in these actions is unknown. Immunohistochemical and w estern blot analysis were used to determine the expression and activation of STAT 5a and STAT 5b throughout the hypothalamus in adult wild‐type and STAT 5b‐deficient mice. Both groups were pretreated with bromocriptine to suppress endogenous prolactin levels followed by the administration of ovine prolactin (10 mg/kg) for 45 min. STAT 5a and STAT 5b were expressed throughout the hypothalamus of wild‐type mice. As expected, only STAT 5a was detected in STAT 5b‐deficient mice, although, unexpectedly, there was a marked reduction in its expression compared to wild‐type mice. When stimulated with prolactin, phosphorylated STAT 5 was observed in the hypothalamus of wild‐type but not STAT 5b‐deficient mice. By contrast, phosphorylated STAT 5 was detected in mammary gland epithelial cells and adipocytes of STAT 5b‐deficient animals. Thus, although STAT 5a was still expressed in the STAT 5b‐deficient mice, it was not phosphorylated in the hypothalamus in response to prolactin. These observations indicate that STAT 5b but not STAT 5a is the primary mediator of the action of prolactin in the hypothalamus. Despite the similarity between the two STAT 5 isoforms, STAT 5a was unable to compensate for the absence of STAT 5b, suggesting that each isoform exhibits a unique biological activity.