Wnt-4 deficiency alters mouse adrenal cortex function, reducing aldosterone production.

Wnt-4 is a signaling factor with multiple roles in organogenesis, a deficiency that leads to abnormal development of the kidney, pituitary gland, female reproductive system, and mammary gland. Wnt-4 is expressed in the cortical region of the developing adrenal gland from embryonic d 11.5 onward, especially in the outermost part. Expression of Cyp11B2 and preadipocyte factor 1 is lowered in the glands of Wnt-4 mutant animals, resulting in significantly reduced aldosterone production in the newborn mutants, suggesting that Wnt-4 may be needed for proper formation of the zona glomerulosa. On the other hand, both proopiomelanocortin-derived peptide beta-endorphin and corticosterone concentration levels are elevated in Wnt-deficient mice, and the expression of Cyp17 is altered in Wnt-4 mutant females, so that it mimics the pattern specific for males. Finally, some cells that are positive for Cyp21, which is normally expressed only in the adrenal gland, are found in the gonads of Wnt-4-deficient embryos, indicating that Wnt-4 may play a role in cell migration or in the sorting of adrenal and gonadal cells during early development. In summary, these results point to a role for Wnt-4 in adrenal gland development and function.