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FoxO1 is a negative regulator of FSHβ gene expression in basal and GnRH-stimulated conditions in female.

 Young Suk Choi  ;  Hyeon Jeong Lee  ;  Cheol Ryong Ku  ;  Yoon Hee Cho  ;  Mi Ran Seo  ;  Yoo Jeoung Lee  ;  Eun Jig Lee 
 ENDOCRINOLOGY, Vol.155(6) : 2277-2286, 2014 
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Animals ; Blotting, Western ; Cells, Cultured ; Electrophoretic Mobility Shift Assay ; Female ; Fluorescent Antibody Technique ; Follicle Stimulating Hormone, beta Subunit/genetics ; Follicle Stimulating Hormone, beta Subunit/metabolism* ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/metabolism* ; Gene Expression Regulation* ; Gonadotropin-Releasing Hormone/pharmacology* ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism* ; Pituitary Gland, Anterior/drug effects ; Pituitary Gland, Anterior/metabolism ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction
The importance of forkhead box class O (FoxO) proteins in reproductive endocrinology has been confirmed by age-dependent infertility in females in a FoxO3a-knockout mouse model. In this study, FoxO1 was detected in gonadotropes in the anterior pituitary. Overexpression of FoxO1 in primary pituitary cells decreased FSHβ gene expression in both basal and GnRH-stimulated conditions, and this result was replicated by the human FSHβ promoter activity. Although direct binding of FoxO1 to FoxO-binding element (FBE) (at -124 to -119 bp of the human FSHβ promoter) was not detected in an electrophoretic mobility shift assay, a DNA pull-down assay and transfection study using the mutant FBE reporter vector revealed that FBE is necessary in FSHβ suppression by FoxO1, suggestive of other cofactor requirements. GnRH stimulated the phosphoinositide 3-kinase pathway, which induced posttranslational modification of FoxO1 and retained it in the cytoplasm. We also confirmed this result in primary cell cultures; most of the FoxO1 was detected in the cytoplasm when treated with GnRH but in the nucleus when the phosphoinositide 3-kinase pathway was inhibited. These findings suggest that FoxO1 is regulated by the GnRH signaling pathway and functions as a negative regulator of FSHβ gene expression.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
5. Research Institutes (연구소) > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease (뇌심혈관질환융합연구사업단) > 1. Journal Papers
5. Research Institutes (연구소) > Institute of Endocrinology (내분비연구소) > 1. Journal Papers
Yonsei Authors
Ku, Cheol Ryong(구철룡) ORCID logo https://orcid.org/0000-0001-8693-9630
Seo, Mi Ran(서미란)
Lee, Yoo Jeong(이유정)
Lee, Eun Jig(이은직) ORCID logo https://orcid.org/0000-0002-9876-8370
Lee, Hyeon Jeong(이현정) ORCID logo https://orcid.org/0000-0003-0635-5454
Cho, Yoon Hee(조윤희)
Choi, Young Suk(최영숙) ORCID logo https://orcid.org/0000-0003-4930-8455
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