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Publication : Development of sexual dimorphism of skeletal muscles through the adrenal cortex, caused by androgen-induced global gene suppression.

First Author  Takahashi F Year  2024
Journal  Cell Rep Volume  43
Issue  2 Pages  113715
PubMed ID  38306273 Mgi Jnum  J:346152
Mgi Id  MGI:7613976 Doi  10.1016/j.celrep.2024.113715
Citation  Takahashi F, et al. (2024) Development of sexual dimorphism of skeletal muscles through the adrenal cortex, caused by androgen-induced global gene suppression. Cell Rep 43(2):113715
abstractText  The zona fasciculata (zF) in the adrenal cortex contributes to multiple physiological actions through glucocorticoid synthesis. The size, proliferation, and glucocorticoid synthesis characteristics are all female biased, and sexual dimorphism is established by androgen. In this study, transcriptomes were obtained to unveil the sex differentiation mechanism. Interestingly, both the amount of mRNA and the expressions of nearly all genes were higher in females. The expression of Nr5a1, which is essential for steroidogenic cell differentiation, was also female biased. Whole-genome studies demonstrated that NR5A1 regulates nearly all gene expression directly or indirectly. This suggests that androgen-induced global gene suppression is potentially mediated by NR5A1. Using Nr5a1 heterozygous mice, whose adrenal cortex is smaller than the wild type, we demonstrated that the size of skeletal muscles is possibly regulated by glucocorticoid synthesized by zF. Taken together, considering the ubiquitous presence of glucocorticoid receptors, our findings provide a pathway for sex differentiation through glucocorticoid synthesis.
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