WCRB2014 POSTER PRESENTATIONS (1) (335 abstracts)
GATA4 serine 105 phosphorylation is required for testicular steroidogenesis in the mouse
Robert Viger 1 , Alain Boulende Sab 2 , Marie France Bouchard 1 , Francis Bergeron 1 , Catherine Brousseau 1 , Jacques J Tremblay 1 & Nicolas Pilon 2
1Laval University, Quebec City, Quebec, Canada; 2Université du Québec à Montréal, Montreal, Quebec, Canada.
GATA4 is a transcription factor required for testicular differentiation and for male fertility. In spite of its crucial roles in male reproduction, how the activity of this factor is regulated has yet to be fully understood. The GATA4 protein is phosphorylated on at least two serine residues. This includes GATA4 S105, which has been reported to modulate GATA4 transcriptional activity in cell line studies. Its contribution to endogenous GATA4 activity in the testis, however, has not been investigated.
To gain insight into the physiological role of GATA4 S105 phosphorylation, we examined GATA4 S105A male mice, which carry a Ser to Ala mutation preventing phosphorylation at this site. A breeding trial and hormonal profiling were used to assess the fertility and endocrine status of GATA4 S105A mutant males. Gene expression and immunohistochemistry experiments were then used to characterize the testicular phenotype associated with the S105A mutation.
While the fertility of homozygous GATA4 S105A adult males was normal, the weights of several androgen-dependent organs (epididymis, seminal vesicle, and prostate) were noticeably smaller when compared to WT controls. This suggested a possible defect in androgen production and/or action. An examination of serum testosterone levels showed a significant 70% decrease in adult S105A males. This decrease was associated with a significant reduction in Star, Cyp11a1, Hsd3b1/6, Cyp17a1, and Hsd17b3 mRNA and protein levels in GATA4 S105A mutant testis. These results provide the first demonstration that GATA4 via S105 phosphorylation is essential for testicular testosterone production via control of multiple genes in the steroidogenic pathway.
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Reproduction Abstracts
ISSN 2052-1472 (online)
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