Differential expression of steroidogenic factor-1/adrenal 4 binding protein and liver receptor homolog-1 (LRH-1)/fetoprotein transcription factor in the rat testis: LRH-1 as a potential regulator of testicular aromatase expression

Vincenzo Pezzi, Rosa Sirianni, Adele Chimento, Marcello Maggiolini, Sonia Bourguiba, Christelle Delalande, Serge Carreau, Sebastiano Ando, Evan R. Simpson, Colin D. Clyne

Research output: Contribution to journalArticle

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Abstract

Aromatase converts testicular androgens to estrogens, which are essential for male fertility. Aromatase expression in testis occurs via transcription from promoter II, and requires the presence of a nuclear receptor half-site that binds the orphan receptor steroidogenic factor-1 [SF-1 (nuclear receptor 5A1)] to mediate basal and (in part) cAMP-induced transcription. We hypothesized that liver receptor homolog-1 (LRH-1) (nuclear receptor 5A2), a receptor closely related to SF-1, could also play a role in regulating aromatase expression in the testis. We demonstrate expression of LRH-1 in adult rat and immature mouse Leydig cells (LHR-1 > SF-1) as well as in pachytene spermatocytes and round spermatids but not in Sertoli cells, which in contrast, express high levels of SF-1. In transient transfection assays using TM3 Leydig cells and TM4 Sertoli cells, a rat promoter II luciferase reporter construct was stimulated by cotransfection of LRH-1 expression vector. Mutation analysis showed that induction by LRH-1 in TM3 and TM4 cells requires an AGGTCA motif at position -90, to which LRH-1 bound in gel shift analysis. We therefore provide evidence that LRH-1 plays an important role in the regulation of aromatase expression in Leydig cells. The colocalization of LRH-1 and aromatase to multiple testis cell types suggests that LRH-1 may have important effects on estrogen production, testis development, spermatogenesis, and testicular carcinogenesis.

Original languageEnglish (US)
Pages (from-to)2186-2196
Number of pages11
JournalEndocrinology
Volume145
Issue number5
DOIs
StatePublished - May 2004

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Steroidogenic Factor 1
Aromatase
Testis
Liver
Leydig Cells
Cytoplasmic and Nuclear Receptors
Sertoli Cells
Estrogens
Spermatocytes
Spermatids
fetoprotein transcription factor
rat NR5A2 protein
Electrophoretic Mobility Shift Assay
Spermatogenesis
Luciferases
Androgens
Transfection
Fertility
Carcinogenesis
Mutation

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Differential expression of steroidogenic factor-1/adrenal 4 binding protein and liver receptor homolog-1 (LRH-1)/fetoprotein transcription factor in the rat testis : LRH-1 as a potential regulator of testicular aromatase expression. / Pezzi, Vincenzo; Sirianni, Rosa; Chimento, Adele; Maggiolini, Marcello; Bourguiba, Sonia; Delalande, Christelle; Carreau, Serge; Ando, Sebastiano; Simpson, Evan R.; Clyne, Colin D.

In: Endocrinology, Vol. 145, No. 5, 05.2004, p. 2186-2196.

Research output: Contribution to journalArticle

Pezzi, Vincenzo ; Sirianni, Rosa ; Chimento, Adele ; Maggiolini, Marcello ; Bourguiba, Sonia ; Delalande, Christelle ; Carreau, Serge ; Ando, Sebastiano ; Simpson, Evan R. ; Clyne, Colin D. / Differential expression of steroidogenic factor-1/adrenal 4 binding protein and liver receptor homolog-1 (LRH-1)/fetoprotein transcription factor in the rat testis : LRH-1 as a potential regulator of testicular aromatase expression. In: Endocrinology. 2004 ; Vol. 145, No. 5. pp. 2186-2196.
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