Wt1 Is Involved in Leydig Cell Steroid Hormone Biosynthesis by Regulating Paracrine Factor Expression in Mice1

Wilms tumor gene, Wt1, is abundantly expressed in testis Sertoli cells. Our recent study demonstrated that Wt1 is involved in spermatogenesis by regulating Sertoli cell polarity. In the present study, we found that Wt1 is also required for steroidogenesis in Leydig cells and that deletion of the Wt1 gene resulted in defects in testosterone biosynthesis and downregulation of steroidogenic gene expression, including cytochrome P450 side-chain cleavage (P450scc), steroidogenic acute regulatory protein (StAR), 3beta-hydroxysteroid dehydro-genase I (3beta-HSD), and cytochrome P450 17A1 (Cyp17a1). The expression of LHR was significantly decreased in Wt1/flox; Cre-ERTM testes after tamoxifen induction, whereas the lutein-izing hormone level in serum was unchanged. Further studies revealed that desert hedgehog (Dhh) expression was regulate