Leydig cell-specific DAX1-deleted mice has higher testosterone level in the testis during pubertal development

Abstract

Testosterone, the male sex hormone, is necessary for the development and function of the male reproductive system. Biosynthesis of testosterone in mammals mainly occurs in testicular Leydig cells. Many proteins such as P450c17, 3β-HSD, and StAR are involved in testicular steroidogenesis. DAX1 is essential for sex development and interacts with nuclear receptors such as steroidogenic factor 1 to inhibit steroidogenesis. In this study, we investigated the role of DAX1 in testicular steroidogenesis in vivo by generating Leydig cell-specific DAX1-knockout mice. Radioimmunoassay revealed that the levels of testosterone and progesterone were higher in Leydig cell-specific DAX1-knockout testes than in the testes from wild-type mice during the first 3-4 weeks of aging. In addition, the expression levels of steroidogenic genes, such as StAR, P450c17, P450scc, and 3β-HSD, were considerably higher in the testes from DAX1-knockout mice. DAX1-deficient mouse testes seemed to attain early puberty with the acceleration of germ cell development. These data suggest that DAX1 regulates the expression of steroidogenic genes, and thereby controls and fine-tunes steroidogenesis during testis development.