title: 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.
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.
authors.affiliation: Department of Pharmaco-Biology, University of Calabria, Arcavacata di Rende 87036 (CS), Italy. v.pezzi@unical.it
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Pezzi
authors.forename: Rosa
authors.initials: R
authors.lastname: Sirianni
authors.forename: Adele
authors.initials: A
authors.lastname: Chimento
authors.forename: Marcello
authors.initials: M
authors.lastname: Maggiolini
authors.forename: Sonia
authors.initials: S
authors.lastname: Bourguiba
authors.forename: Christelle
authors.initials: C
authors.lastname: Delalande
authors.forename: Serge
authors.initials: S
authors.lastname: Carreau
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Andò
authors.forename: Evan R
authors.initials: ER
authors.lastname: Simpson
authors.forename: Colin D
authors.initials: CD
authors.lastname: Clyne
mesh_terms: D000818:Animals; D001141:Aromatase / Q000235:genetics*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D051717:Fushi Tarazu Transcription Factors; D005786:Gene Expression Regulation / Q000187:drug effects; D018398:Homeodomain Proteins; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D016296:Mutagenesis; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012708:Sertoli Cells / Q000378:metabolism; D013087:Spermatids / Q000378:metabolism; D013090:Spermatocytes / Q000378:metabolism; D054339:Steroidogenic Factor 1; D013737:Testis / Q000737:chemistry / Q000201:enzymology*; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; C417002:NR5A2 protein, rat; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C099948:fetoprotein transcription factor; C515058:steroidogenic factor 1, mouse; C515060:steroidogenic factor 1, rat; D004247:DNA; D001141:Aromatase