Liver receptor homolog-1 regulates the expression of steroidogenic acute regulatory protein in human granulosa cells

Joung Woul Kim, Noel Peng, William E. Rainey, Bruce R. Carr, George R. Attia

Research output: Contribution to journalArticle

51 Citations (Scopus)

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 sex 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.

Original languageEnglish (US)
Pages (from-to)3042-3047
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume89
Issue number6
DOIs
StatePublished - Jun 2004

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Granulosa Cells
Liver
Regulator Genes
Cyclic AMP-Dependent Protein Kinases
Gene expression
Gene Expression
Steroid hormones
Granulosa Cell Tumor
X-Linked Genes
Mutation
Sex Chromosomes
steroidogenic acute regulatory protein
Chromosomes, Human, Pair 1
Chromosomes
Ovulation
Transfection
Tumors
Transcription Factors
Genes
Steroids

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Liver receptor homolog-1 regulates the expression of steroidogenic acute regulatory protein in human granulosa cells. / Kim, Joung Woul; Peng, Noel; Rainey, William E.; Carr, Bruce R.; Attia, George R.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 89, No. 6, 06.2004, p. 3042-3047.

Research output: Contribution to journalArticle

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