Steroidogenesis in zebrafish and mouse models

Steroid hormones regulate physiological homeostasis for salt, sugar, and sex differentiation. All steroids are synthesized from a common precursor, cholesterol, in a step that converts cholesterol to pregnenolone. The enzyme carrying out this first conversion step is CYP11A1. To further investigate the importance of steroid biosynthesis, animal models with defects in the Cyp11a1 gene are used. Mice with targeted disruption of the Cyp11a1 gene produce no steroids with severe adrenal defects. These mice survive during embryogenesis, but die after birth. Zebrafish with a block in cyp11a1 gene function has an earlier defect, presumably because it lacks adequate maternal steroid supply. When cyp11a1 activity was compensated by the injection of antisense morpholino oligos, the embryos have shortened axis and a defect of epibolic cell movement during early embryogenesis. The discovery of steroid function in cell movement is novel, and should provide new insights into our understanding of diverse functions of steroids.