Figure 1.

Model illustrating the morphological alterations and pathway deregulation in the adrenal gland of FGD type 2. In the normal adrenal cortex, activation of SHH and WNT4 signalling results in driving the expression of CYP11B2, DAB2 and LEF1 leading to a zona glomerulosa (ZG) lineage. Activation of PKA due to the action of ACTH on MC2R/MRAP complex suppresses WNT4 resulting in inhibition of CYP11B2, DAB2 and LEF1 and differentiation into ZF cells. In FGD type 2 (Mrap^−/− mice) adrenal glands, the lack of PKA activation results in complete absence of ZF and WNT4/SHH accumulation outside the ZG, where WNT4 expression in such cells do not lead to a functional ZG identity. Morphologically the ZG is expanded and is able to secrete aldosterone. The adrenal medulla in FGD type 2 is morphologically intact and secretes both epinephrine and norepinephrine.