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Sexually dimorphic expression of Dax‐1 in the adrenal cortex
Author(s) -
Mukai Tokuo,
Kusaka Masatomo,
Kawabe Ken,
Goto Kiminobu,
Nawata Hajime,
Fujieda Kenji,
Morohashi Kenichirou
Publication year - 2002
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1046/j.1365-2443.2002.00556.x
Subject(s) - biology , androgen receptor , adrenal cortex , androgen , gene expression , nuclear receptor , gene , regulation of gene expression , hypogonadotropic hypogonadism , transcription factor , endocrinology , medicine , microbiology and biotechnology , genetics , prostate cancer , cancer , hormone
Background: The DAX‐1 (also known as AHC ) gene encodes an unusual member of the nuclear receptor superfamily, and the gene product plays a pivotal role during gonadal and adrenal differentiation. Mutations of the human DAX‐1 gene cause X‐linked adrenal hypoplasia congenita associated with hypogonadotropic hypogonadism. However, the molecular mechanisms underlying the transcriptional regulation of the gene are not well understood. Results: Sexually dimorphic expression of Dax‐1 (NR0B1) in the adrenal cortex was observed by RT‐PCR, Western blotting and immunohistochemistry. The differential expression was abolished by gonadectomy and was restored again by sex steroid replacement. Our results suggested that the Dax‐1 gene transcription is suppressed by androgens and androgen receptor (AR/NR3C4). Dax‐1 gene transcription is regulated by Ad4BP/SF‐1 (NR5A1), therefore we investigated the functional correlation between A4BP/SF‐1 and AR. Interestingly, AR down‐regulated the Dax‐1 gene transcription mediated by Ad4BP/SF‐1 in the presence of the ligand. DNA binding by AR was not essential for the suppressive action, however the suppression seemed to be dependent on the promoter contexts. An interaction between Ad4BP/SF‐1 and AR was detected in the presence of the ligand for AR. Conclusion: The present study revealed that the expression of Dax‐1 in the adrenal cortex is regulated by androgen and the receptor. Interestingly, AR acts as a suppressor in the presence of the ligand through interaction with Ad4BP/SF‐1.