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

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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 β124 to β119 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.

Original languageEnglish
Pages (from-to)2277-2286
Number of pages10
JournalEndocrinology
Volume155
Issue number6
DOIs
Publication statusPublished - 2014 Jun

All Science Journal Classification (ASJC) codes

  • Endocrinology

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