Shima, Yuichi Miyabayashi, Kanako Mori, Takami Ono, Koji Kajimoto, Mizuki Cho, Hae Lim Tsuchida, Hitomi Uenoyama, Yoshihisa Tsukamura, Hiroko Suzuki, Kentaro Choi, Man Ho Toida, Kazunori 2024-01-19T10:31:05Z 2024-01-19T10:31:05Z 2023-01-26 2023-01 1661-6596 https://pubs.kist.re.kr/handle/201004/114149 Nuclear receptor subfamily 5 group A member 1 (NR5A1) is expressed in the pituitary gonadotrope and regulates their differentiation. Although several regulatory regions were implicated in Nr5a1 gene expression in the pituitary gland, none of these regions have been verified using mouse models. Furthermore, the molecular functions of NR5A1 in the pituitary gonadotrope have not been fully elucidated. In the present study, we generated mice lacking the pituitary enhancer located in the 6th intron of the Nr5a1 gene. These mice showed pituitary gland-specific disappearance of NR5A1, confirming the functional importance of the enhancer. Enhancer-deleted male mice demonstrated no defects at fetal stages. Meanwhile, androgen production decreased markedly in adult, and postnatal development of reproductive organs, such as the seminal vesicle, prostate, and penis was severely impaired. We further performed transcriptomic analyses of the whole pituitary gland of the enhancer-deleted mice and controls, as well as gonadotropes isolated from Ad4BP-BAC-EGFP mice. These analyses identified several genes showing gonadotrope-specific, NR5A1-dependent expressions, such as Spp1, Tgfbr3l, Grem1, and Nr0b2. These factors are thought to function downstream of NR5A1 and play important roles in reproductive organ development through regulation of pituitary gonadotrope functions. English Multidisciplinary Digital Publishing Institute (MDPI) Intronic Enhancer Is Essential for Nr5a1 Expression in the Pituitary Gonadotrope and for Postnatal Development of Male Reproductive Organs in a Mouse Model Article 10.3390/ijms24010192 1 International Journal of Molecular Sciences, v.24, no.1 International Journal of Molecular Sciences 24 1 Y scie scopus 000910239000001 2-s2.0-85145976121 Biochemistry & Molecular Biology Chemistry, Multidisciplinary Biochemistry & Molecular Biology Chemistry Article STEROIDOGENIC FACTOR-I TARGETED DISRUPTION GENE-TRANSCRIPTION RESPONSE ELEMENT AD4BP/SF-1 HORMONE DAX-1 FACTOR-1 IDENTIFICATION PROMOTER enhancer pituitary gonadotrope luteinizing hormone follicle-stimulating hormone