Liver receptor homolog-1 regulates the expression of steroidogenic acute regulatory protein in human granulosa cells.
J Clin Endocrinol Metab
; 89(6): 3042-7, 2004 Jun.
Article
em En
| MEDLINE
| ID: mdl-15181096
ABSTRACT
Steroidogenic acute regulatory protein (StAR) plays a critical role in the initial step of steroid hormone synthesis. In the present study, we investigated the role of liver receptor homolog-1 (LRH-1) and dosage-sensitive sex reversal, adrenal hypoplasia congenital critical region on the X chromosome, gene 1 (DAX-1) in the regulation of StAR gene expression in human granulosa cell tumor cells. We also examined the effect of protein kinase A (PKA) signaling pathway on the expression of StAR in the presence of LRH-1 and DAX-1. Cell transfection, mutation analysis, and EMSA were performed. LRH-1 significantly induced StAR promoter activity in a concentration-dependent manner. This induction was further augmented in the presence of PKA agonist. Using deletion analysis, we demonstrated LRH-1 binding site at -105/-95. Mutation of this site resulted in a significant decrease in the StAR promoter activity. Using EMSA, the ability of this cis-element to bind LRH-1 was confirmed. DAX-1 inhibited LRH-1-stimulated StAR promoter activity in a concentration-dependent manner. This inhibition was also maintained in the presence of PKA stimulation. Our results demonstrated that LRH-1 plays a critical role in the induction of StAR gene expression. We hypothesize that LRH-1 could be the major transcription factor responsible for the rapid and significant increase in ovarian StAR gene expression after ovulation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ovário
/
Fosfoproteínas
/
Receptores Citoplasmáticos e Nucleares
Limite:
Female
/
Humans
Idioma:
En
Revista:
J Clin Endocrinol Metab
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos