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.
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.
Pezzi
Vincenzo
V
Department of Pharmaco-Biology, University of Calabria, Arcavacata di Rende 87036 (CS), Italy. v.pezzi@unical.it
Sirianni
Rosa
R
Chimento
Adele
A
Maggiolini
Marcello
M
Bourguiba
Sonia
S
Delalande
Christelle
C
Carreau
Serge
S
Andò
Sebastiano
S
Simpson
Evan R
ER
Clyne
Colin D
CD
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
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