Fig. 6.

Sex-specific effects of Rspo1 overexpression in the adrenal cortex. Localized expression of R-spondins (by the capsule) maintains high levels of WNT/β-catenin signaling and proliferation in the outer cortex. Ectopic expression of Rspo1 by steroidogenic cells leads to increased WNT/β-catenin signaling in the inner cortex, as indicated by ectopic expression of Wnt4 and Axin2, and ectopic proliferation that causes adrenocortical hyperplasia and fragmentation of the medulla (M). On the contrary, in male adrenals or in female adrenals treated with androgens (DHT), ectopic Rspo1 causes differential effects on Wnt4 and Axin2 expression, whereas ectopic proliferation is prevented via activation of AR signaling.