Adrenal cortex size, homeostasis and tumorigenesis is regulated by gonadal hormones via androgen receptor/β-catenin signalling crosstalk.
Lyraki, R.; Grabek, A.; Tison, A.; Peitzsch, M.; Bechmann, N.; Youssef, S.; de Bruin, A.; Bakker, E.; Claessens, F.; Chaboissier, M.-C.; Schedl, A.
Show abstract
Female bias is highly prevalent among adrenal cortex hyperplasia and neoplasia, but the reasons behind this phenomenon are poorly understood. In this article, we show that overexpression of the secreted WNT agonist R-spondin-1 leads to ectopic activation of WNT/{beta}-catenin signalling and causes sex-specific adrenocortical hyperplasia in mice. While female adrenals show ectopic proliferation, male adrenals display excessive immune system activation and cortical thinning. Using a combination of genetic manipulations and hormonal treatment, we show that gonadal androgens suppress ectopic proliferation in the adrenal cortex and determine the selective activation of WNT-related genes Axin2 and Wnt4. Notably, genetic removal of androgen receptor (AR) from adrenocortical cells restores the mitogenic effect of WNT/{beta}-catenin signalling. This is the first demonstration that AR activity in the adrenal cortex determines susceptibility to canonical WNT signalling-induced hyperplasia. TeaserActivation of R-spondin signaling in the adrenal cortex leads to a sexually dimorphic phenotype causing tumors in females and immune cell recruitment in males
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Astrocyte glucocorticoid receptors mediate sex-specific changes in activity following stress 93%
- NR2F2 regulation of interstitial to fetal Leydig cell differentiation in the testis: insights into differences of sex development 93%
- TRIM28-dependent SUMOylation protects the adult ovary from the testicular pathway 93%
Similar papers in this journal
- Reduced NCOR2 expression accelerates androgen deprivation therapy failure in prostate cancer 93%
- Atrial natriuretic peptide orchestrates a coordinated physiological response to fuel non shivering thermogenesis 92%
- Single-cell transcriptomic profiling redefines the origin and specification of early adrenogonadal progenitors 92%
Similar papers in this journal
- Sex-specific thermoregulatory effects of estrogen signaling in Reprimo lineage cells 92%
- Disease-associated mutations in the STAT5B SH2 domain reprogram hepatic cholesterol and lipid metabolism 92%
- NEDD4 promotes Sertoli cell proliferation and adult Leydig cell differentiation in the murine testis 91%
Similar papers in this journal
- Claudin-11 regulates immunological barrier formation and spermatogonial proliferation through stem cell factor 92%
- The transcriptomic landscape of monosomy X (45,X) during early human fetal and placental development 91%
- gp130/STAT3 signaling is required for homeostatic proliferation and anabolism in postnatal growth plate and articular chondrocytes 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.