z-logo
Premium
Phosphorylation of GATA 4 serine 105 but not serine 261 is required for testosterone production in the male mouse
Author(s) -
Bergeron F.,
Boulende Sab A.,
Bouchard M. F.,
Taniguchi H.,
Souchkova O.,
Brousseau C.,
Tremblay J. J.,
Pilon N.,
Viger R. S.
Publication year - 2019
Publication title -
andrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.947
H-Index - 43
eISSN - 2047-2927
pISSN - 2047-2919
DOI - 10.1111/andr.12601
Subject(s) - biology , serine , phosphorylation , androgen , transcription factor , medicine , endocrinology , testosterone (patch) , steroidogenic factor 1 , gene knockdown , sexual differentiation , gene , cholesterol side chain cleavage enzyme , microbiology and biotechnology , andrology , hormone , messenger rna , genetics , nuclear receptor
Background GATA 4 is a transcription factor essential for male sex determination, testicular differentiation during fetal development, and male fertility in the adult. GATA 4 exerts part of its function by regulating multiple genes in the steroidogenic enzyme pathway. In spite of these crucial roles, how the activity of this factor is regulated remains unclear. Objectives Studies in gonadal cell lines have shown that GATA 4 is phosphorylated on at least two serine residues—serine 105 (S105) and serine 261 (S261)—and that this phosphorylation is important for GATA 4 activity. The objective of the present study is to characterize the endogenous role of GATA 4 S105 and S261 phosphorylation in the mouse testis. Materials and methods We examined both previously described GATA 4 S105A mice and a novel GATA 4 S261A knock‐in mouse that we generated by CRISPR /Cas9 gene editing. The male phenotype of the mutants was characterized by assessing androgen‐dependent organ weights, hormonal profiles, and expression of multiple testicular target genes using standard biochemical and molecular biology techniques. Results The fecundity of crosses between GATA 4 S105A mice was reduced but without a change in sex ratio. The weight of androgen‐dependent organs was smaller when compared to wild‐type controls. Plasma testosterone levels showed a 70% decrease in adult GATA 4 S105A males. This decrease was associated with a reduction in Cyp11a1 , Cyp17a1 , and Hsd17b3 expression. GATA 4 S261A mice were viable and testis morphology appeared normal. Testosterone production and steroidogenic enzyme expression were not altered in GATA 4 S261A males. Discussion and conclusion Our analysis showed that blocking GATA 4 S105 phosphorylation is associated with decreased androgen production in males. In contrast, S261 phosphorylation by itself is dispensable for GATA 4 function. These results confirm that endogenous GATA 4 action is essential for normal steroid production in males and that this activity requires phosphorylation on at least one serine residue.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here