Estradiol and tamoxifen regulate NRF-1 and mitochondrial function in mouse mammary gland and uterus
| dc.contributor.author | Ivanova, Margarita M. | |
| dc.contributor.author | Radde, Brandie N. | |
| dc.contributor.author | Son, Jieun | |
| dc.contributor.author | Mehta, Fabiola F. | |
| dc.contributor.author | Chung, Sang-Hyuk | |
| dc.contributor.author | Klinge, Carolyn M. | |
| dc.date.accessioned | 2020-03-10T17:12:04Z | |
| dc.date.available | 2020-03-10T17:12:04Z | |
| dc.date.issued | 2014-5 | |
| dc.description.abstract | Nuclear respiratory factor-1 (NRF-1) stimulates the transcription of nuclear-encoded genes that regulate mitochondrial (mt) genome transcription and biogenesis. We reported that estradiol (E2) and 4-hydroxytamoxifen (4-OHT) stimulate NRF-1 transcription in an estrogen receptor ? (ER?)- and ER?-dependent manner in human breast cancer cells. The aim of this study was to determine whether E2 and 4-OHT increase NRF-1 in vivo. Here, we report that E2 and 4-OHT increase NRF-1 expression in mammary gland (MG) and uterus of ovariectomized C57BL/6 mice in a time-dependent manner. E2 increased NRF-1 protein in the uterus and MG; however, in MG, 4-OHT increased Nrf1 mRNA but not protein. Chromatin immunoprecipitation assays revealed increased in vivorecruitment of ER? to the Nrf1 promoter and intron 3 in MG and uterus 6 h after E2 and 4-OHT treatment, commensurate with increased NRF-1 expression. E2- and 4-OHT-induced increases in NRF-1 and its target genes Tfam, Tfb1m, and Tfb2m were coordinated in MG but not in uterus due to uterine-selective inhibition of the expression of the NRF-1 coactivators Ppargc1a and Ppargc1b by E2 and 4-OHT. E2 transiently increased NRF-1 and PGC-1? nuclear staining while reducing PGC-1? in uterus. E2, not 4-OHT, activates mt biogenesis in MG and uterus in a time-dependent manner. E2 increased mt outer membrane Tomm40 protein levels in MG and uterus whereas 4-OHT increased Tomm40 only in uterus. These data support the hypothesis of tissue-selective regulation of NRF-1 and its downstream targets by E2 and 4-OHT in vivo. | |
| dc.identifier.citation | Copyright 2013 Journal of Molecular Endocrinology. This is a post-print version of a published paper that is available at: https://jme.bioscientifica.com/view/journals/jme/51/2/233.xml. Recommended Citation: Ivanova, M. M., B. N. Radde, J. Son, F. F. Mehta, S. H. Chung, and C. M. Klinge. "Estradiol and tamoxifen regulate NRF-1 and mitochondrial function in mouse mammary gland and uterus." Journal of molecular endocrinology 51, no. 2 (2013): 233. DOI: 10.1530/JME-13-0051. This item has been deposited in accordance with publisher copyright and licensing terms and with the author's permission. | |
| dc.identifier.uri | https://hdl.handle.net/10657/5929 | |
| dc.language.iso | en_US | |
| dc.publisher | Journal of Molecular Endocrinology | |
| dc.subject | nuclear respiratory factor-1 | |
| dc.subject | estrogen receptor | |
| dc.subject | mitochondria | |
| dc.subject | mouse | |
| dc.title | Estradiol and tamoxifen regulate NRF-1 and mitochondrial function in mouse mammary gland and uterus | |
| dc.type | Article |