Affordable Access

deepdyve-link
Publisher Website

FoxL2 Is required for activin induction of the mouse and human follicle-stimulating hormone beta-subunit genes.

Authors
  • Corpuz, Patrick S1
  • Lindaman, Lacey L
  • Mellon, Pamela L
  • Coss, Djurdjica
  • 1 Department of Reproductive Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093-0674, USA.
Type
Published Article
Journal
Molecular Endocrinology
Publisher
The Endocrine Society
Publication Date
May 2010
Volume
24
Issue
5
Pages
1037–1051
Identifiers
DOI: 10.1210/me.2009-0425
PMID: 20233786
Source
Medline
License
Unknown

Abstract

Activin is a major physiological regulator of FSH. We identify FoxL2 as a critical component in activin induction of FSHbeta, both for the mouse gene, induction of which is Sma- and Mad-related protein (Smad) dependent, and for the human gene that is Smad independent. FoxL2 has been shown to regulate gonadotrope gene expression (GnRH receptor, alpha-glycoprotein subunit, porcine FSHbeta, and follistatin), but the mechanisms of action are not well understood. We identify novel sites required for activin action in both the mouse and human FSHbeta promoters, some of which bind FoxL2, and show that the FoxL2-binding element encompasses a larger region (12 bp) than the previously identified forkhead-binding consensus (7 bp). Remarkably, although required for activin induction, FoxL2 sites neither contribute to basal FSHbeta promoter activity nor confer activin response to a heterologous promoter; thus, they are neither classical activin-response elements nor is their role solely to recruit Smads to the promoter. FoxL2 overexpression can potentiate activin induction in gonadotropes and can confer activin responsiveness to FSHbeta in heterologous cells where this promoter is normally refractory to activin induction. Although Smad3 requires the presence of FoxL2 sites to induce mouse FSHbeta, even through its consensus Smad-binding element; the human promoter, which is induced by activin independently of Smad3, also requires FoxL2 sites for its induction by activin; thus the actions of FoxL2 are not exclusively through interactions with the Smad pathway. Thus, FoxL2 plays a key role in activin induction of the FSHbeta gene, by binding to sites conserved across multiple species.

Report this publication

Statistics

Seen <100 times