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PMID: 11328853 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Activation of the rat follicle-stimulating hormone receptor promoter by steroidogenic factor 1 is blocked by protein kinase a and requires upstream stimulatory factor binding to a proximal E box element.

Molecular endocrinology (Baltimore, Md.) ·Vol. 15 ·No. 5 ·2001-05-00 ·Pages 704-15

Heckert LL

Abstract

The receptor for the pituitary glycoprotein hormone FSH (FSHR) and the nuclear hormone receptor steroidogenic factor 1 (SF-1) play important roles in control of the hypothalamic-pituitary- gonadal axis. FSHR is essential for integrating the pituitary FSH signal to gonadal response, while SF-1 is an important transcriptional regulator of many genes that function within this axis and is essential for the development of gonads and adrenal glands. Given the critical role of SF-1 in regulation of the gonads and the coexpression of FSHR and SF-1 in Sertoli and granulosa cells, we examined the ability of SF-1 to regulate transcription of the FSHR gene. We found that SF-1 stimulated rat FSHR promoter activity in a dose-dependent and promoter-specific manner. Examination of various promoter deletion mutants indicated that SF-1 acts through the proximal promoter region and upstream promoter sequences. An E box element within the proximal promoter is essential for activation of the FSHR promoter by SF-1. This element binds the transcriptional regulators USF1 and USF2 (upstream stimulatory factors 1 and 2) but not SF-1, as shown by electrophoretic mobility shift assays. In addition, functional studies identified a requirement for the USF proteins in SF-1 activation of FSHR and mapped an important regulatory domain within exons 4 and 5 of USF2. Cotransfection studies revealed that activation of protein kinase A leads to inhibition of SF-1-stimulated transcription of FSHR, while it synergized with SF-1 to activate the equine LH beta-promoter (ebeta). Thus, stimulation of the cAMP pathway differentially regulates SF-1 activation of the FSHR and ebeta-promoters.

MeSH Terms
Animals Base Sequence Cyclic AMP/metabolism Cyclic AMP-Dependent Protein Kinases/physiology DNA Probes/chemistry DNA-Binding Proteins/antagonists & inhibitors,physiology Electrophoresis, Polyacrylamide Gel Fushi Tarazu Transcription Factors Gene Expression Regulation/physiology Homeodomain Proteins Humans Mice Molecular Sequence Data Mutation Promoter Regions, Genetic/physiology Rats Receptors, Cytoplasmic and Nuclear Receptors, FSH/biosynthesis,genetics,physiology Steroidogenic Factor 1 Transcription Factors/antagonists & inhibitors,metabolism,physiology Transcriptional Activation/physiology Transfection Tumor Cells, Cultured Upstream Stimulatory Factors
Chemicals
DNA Probes DNA-Binding Proteins Fushi Tarazu Transcription Factors Homeodomain Proteins NR5A1 protein, human Receptors, Cytoplasmic and Nuclear Receptors, FSH Steroidogenic Factor 1 Transcription Factors USF1 protein, human USF2 protein, human Upstream Stimulatory Factors Usf1 protein, mouse Usf1 protein, rat Usf2 protein, mouse Usf2 protein, rat steroidogenic factor 1, mouse steroidogenic factor 1, rat Cyclic AMP Cyclic AMP-Dependent Protein Kinases
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Heckert L L
Department of Molecular and Integrative Physiology The University of Kansas Medical Center Kansas City, Kansas 66160, USA. lheckert@kumc.edu
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Article Info
Journal
Molecular endocrinology (Baltimore, Md.)
Abbr.
Mol Endocrinol
ISSN
0888-8809
DOI
10.1210/mend.15.5.0632
Email
lheckert@kumc.edu
Published
2001-05-00
Pages
704-15
Language
English
Region
United States
NLM ID
8801431
PMCID
PMC1496918
Subset
IM
Grants
NICHD NIH HHS · R29 HD035217 · United States
NICHD NIH HHS · R29HD-3521701A1 · United States
External Links
PubMed source DOI: 10.1210/mend.15.5.0632 PMC Full Text View journal details
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