Takahashi, Fumiya Baba, Takashi Christianto, Antonius Yanai, Shogo Lee-Okada, Hyeon-Cheol Ishiwata, Keisuke Nakabayashi, Kazuhiko Hata, Kenichiro Ishii, Tomohiro Hasegawa, Tomonobu Yokomizo, Takehiko Choi, Man Ho Morohashi, Ken-ichirou 2024-04-04T02:01:43Z 2024-04-04T02:01:43Z 2024-04-04 2024-02 2211-1247 https://pubs.kist.re.kr/handle/201004/149571 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. English Cell Press Development of sexual dimorphism of skeletal muscles through the adrenal cortex, caused by androgen-induced global gene suppression Article 10.1016/j.celrep.2024.113715 1 Cell Reports, v.43, no.2 Cell Reports 43 2 Y scie scopus 001179334500001 2-s2.0-85184000838 Cell Biology Cell Biology Article GONADAL HORMONE REPLACEMENT STEROIDOGENIC FACTOR-I ADRENOCORTICAL STRUCTURE TRANSCRIPTION FACTOR NUCLEAR RECEPTOR POSTPUBERTAL GONADECTOMY INTEGRATIVE ANALYSIS NADPH PRODUCTION EXPRESSION RAT