Casein Kinase 1α Regulates Testosterone Synthesis and Testis Development in Adult Mice

Casein kinase 1 alpha (CK1 alpha) is a main component of the Wnt/beta-catenin signaling pathway, which participates in multiple biological processes. Our recent study demonstrated that CK1 alpha is expressed in both germ cells and somatic cells of mouse testes and regulates spermatogenesis. However, little information is known about the role of CK1 alpha in regulating the development of somatic cells in mouse testes. Our results demonstrated that conditional disruption of CK1 alpha 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 CK1 alpha conditional knockout (cKO) mice, while the proliferation of Leydig cells and Sertoli cells was not affected. Furthermore, in vitro results verified that luteinizing hormone upregulates CK1 alpha through the luteinizing hormone/protein kinase/Epidermal Growth Factor Receptor/extracellular regulated protein kinases/2 signaling pathway and that CK1 alpha 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 CK1 alpha in steroidogenesis and male reproduction.