Casein kinase 1α regulates testosterone synthesis and testis development in adult mice.

Casein kinase 1α (CK1α) is one of the main components of the Wnt/β-catenin signalling pathway, which participates in multiple biological processes. Our recent study demonstrated that CK1α is expressed in both germ cells and somatic cells of mouse testes and regulates spermatogenesis. However, little information is known about the role of CK1α in regulating the development of somatic cells in mouse testes. Our results demonstrated that conditional disruption of CK1α in murine Leydig cells sharply decreased testosterone levels; markedly affected testis development, sperm motility, and sperm morphology; and caused subfertility. The germ cell population was partially decreased in CK1α conditional knockout (cKO) mice, while the proliferation of Leydig cells and Sertoli cells was not affected. Furthermore, in vitro results verified that LH upregulates CK1α through the LH/PKA/EGFR/ERK1/2 signalling pathway and that CK1α interacts with and phosphorylates EGFR, which subsequently activates the phosphorylation of ERK1/2, thereby promoting testosterone synthesis. In addition, high dose testosterone propionate partially rescued the phenotype observed in cKO mice. This study provides new insights into the role of CK1α in steroidogenesis and male reproduction.