Combined oral contraceptive synergistically activates mineralocorticoid receptor through histone code modifications

Simple item page
dc.contributor.authorIgunnu, Adedoyin
dc.contributor.authorYoung-Mi, Seok
dc.contributor.authorLawrence, A. Olatunji
dc.contributor.authorSeol-Hee, Kang
dc.contributor.authorInkyeom, Kim
dc.date.accessioned2020-05-25T14:25:19Z
dc.date.available2020-05-25T14:25:19Z
dc.date.issued2015-10-23
dc.description.abstractClinical studies have shown that the use of combined oral contraceptive in pre-menopausal women is associated with fluid retention. However, the molecular mechanism is still elusive. We hypothesized that combined oral contraceptive (COC) ethinyl estradiol (EE) and norgestrel (N) synergistically activates mineralocorticoid receptor (MR) through histone code modifications. Twelve-week-old female Sprague- Dawley rats were treated with olive oil (control), a combination of 0.1 mg EE and 1.0 mg N (low COC) or 1.0 mg EE and 10.0 mg N (high COC) as well as 0.1 or 1.0 mg EE and 1.0 or 10.0 mg N daily for 6 weeks. Expression of MR target genes in kidney cortex was determined by quantitative real-time polymerase chain reaction. MR was quantified by western blot. Recruitment of MR and RNA polymerase II (Pol II) on promoters of target genes as well as histone code modifications was analyzed by chromatin im- munoprecipitation assay. Treatment with COC increased renal cortical expression of MR target genes such as serum and glucocorticoid-regulated kinase 1 (Sgk-1), glucocorticoid-induced leucine zipper (Gilz), epithelial Na þ channel (Enac) and Na þ –K þ –ATPase subunit α 1 (Atp1a1). Although COC increased neither serum aldosterone nor MR expression in kidney cortex, it increased recruitment of MR and Pol II in parallel with increased H3Ac and H3K4me3 on the promoter regions of MR target genes. However, treatment with EE or N alone did not affect renal cortical expression of Sgk-1, Gilz, Enac or Atp1a1. These results indicate that COC synergistically activates MR through histone code modificationsen_US
dc.description.sponsorshipThis research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (2013R1A2A2A01005155, 2013K2A4A1044932 and 2013K2A- 1B9061222, 2014K2A5A3000021, 2014K2A4A1034762 and 2014K1A3A1A09063332), and the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI13C1527).en_US
dc.identifier.issn0014-2999
dc.identifier.urihttp://hdl.handle.net/123456789/4046
dc.publisherElsevieren_US
dc.relation.ispartofseriesEuropean Journal of Pharmacology;
dc.subjectOral contraceptiveen_US
dc.subjectMineralocorticoid receptoren_US
dc.subjectHistone codeen_US
dc.subjectGene transcriptionen_US
dc.titleCombined oral contraceptive synergistically activates mineralocorticoid receptor through histone code modificationsen_US
dc.typeArticleen_US

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
Igunnu et al 2015-Combined oral contraceptive synergistically activates mineralocorticoid receptor through histone code modifications.docx
Size:
12.28 KB
Format:
Microsoft Word XML
Description:
Abstract
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.69 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections