Members of the secreted WNT glycoprotein family are important in embryogenesis and adult tissue homeostasis, and defects in the signal transduction of several WNT ligands including WNT4 have been linked to a variety of clinical conditions. Deletion of Wnt4 gene in mice leads to improper development of many organs including the adrenals in which the zona glomerulosa forms imperfectly. The objective of this study was to investigate the expression of WNT4 in human adult and fetal adrenals and adrenocortical tumours by immunohistochemistry and quantitative real-time RT-PCR. The effects of ACTH and angiotensin II on WNT4 mRNA expression were evaluated by using primary adrenal cell cultures. Immunohistochemistry of normal adult adrenal revealed WNT4 expression in the medulla and to a lesser extent in all adrenocortical zones, the staining being strongest in the zona glomerulosa. The mRNA expression was significantly lower in fetal adrenals as well as in virilizing carcinomas and Cushings adenomas (P<0.05), and higher in Conns adenomas (P<0.01) compared with normal adult adrenals. ACTH induced significantly WNT4 expression after 24 and 48 hours while angiotensin II had no effect on the expression. These data show that WNT4 is expressed in human adrenals and the WNT4 mRNA expression levels are inconstant during the development of the adrenals and in different adrenocortical tumours. The expression is regulated long term by ACTH but not by angiotensin II. The results suggest a possible role for WNT4 in human adrenal function and pathophysiology.
01 - 05 Apr 2006
European Society of Endocrinology