RGD Reference Report - Non-classical testosterone signaling mediated through ZIP9 stimulates claudin expression and tight junction formation in Sertoli cells. - Rat Genome Database

RGD Reference Report - Non-classical testosterone signaling mediated through ZIP9 stimulates claudin expression and tight junction formation in Sertoli cells. - Rat Genome Database

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Non-classical testosterone signaling mediated through ZIP9 stimulates claudin expression and tight junction formation in Sertoli cells.
Authors:	Bulldan, Ahmed Dietze, Raimund Shihan, Mazen Scheiner-Bobis, Georgios
Citation:	Bulldan A, etal., Cell Signal. 2016 Aug;28(8):1075-85. doi: 10.1016/j.cellsig.2016.04.015. Epub 2016 May 6.
RGD ID:	155663545
Pubmed:	PMID:27164415 (View Abstract at PubMed)
DOI:	DOI:10.1016/j.cellsig.2016.04.015 (Journal Full-text)
In the classical signaling pathway, testosterone regulates gene expression by activating the cytosolic/nuclear androgen receptor. In the non-classical pathway, testosterone activates cytosolic signaling cascades that are normally triggered by growth factors. The nature of the receptor involved in this signaling pathway is a source of controversy. In the Sertoli cell line 93RS2, which lacks the classical AR, we determined that testosterone stimulates the non-classical signaling pathway, characterized by the phosphorylation of Erk1/2 and transcription factors CREB and ATF-1. We also demonstrated that testosterone increases the expression of the tight junction (TJ) proteins claudin-1 and claudin-5. Both of these proteins are known to be essential constituents of TJs between Sertoli cells, and as a consequence of their increased expression transepithelial resistance across Sertoli cell monolayers is increased. ZIP9 is a Zn(2+)transporter that was recently shown to be a membrane-bound testosterone receptor. Silencing its expression in 93RS2 Sertoli cells by siRNA completely prevents Erk1/2, CREB, and ATF-1 phosphorylation as well the stimulation of claudin-1 and -5 expression and TJ formation between neighboring cells. The study presented here demonstrates for the first time that in Sertoli cells testosterone acts through the receptor ZIP9 to trigger the non-classical signaling cascade, resulting in increased claudin expression and TJ formation. Since TJ formation is a prerequisite for the maintenance of the blood-testis barrier, the testosterone/ZIP9 effects might be significant for male physiology. Further assessment of these interactions will help to supplement our knowledge concerning the mechanism by which testosterone plays a role in male fertility.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Slc39a9	Rat	bicellular tight junction assembly	involved_in	IMP		PMID:27164415	UniProt
Slc39a9	Rat	regulation of cellular response to testosterone stimulus	involved_in	ISS	UniProtKB:Q8BFU1	PMID:27164415	UniProt

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Genes (Rattus norvegicus)

Slc39a9 (solute carrier family 39, member 9)

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