%0 Generic %A N., Camats %A L., Audí %A M., Fernández-Cancio %A P., Andaluz %A P.E., Mullis %A A., Carrascosa %A C.E., Flück %D 2015 %T Supplementary Material for: LRH-1 May Rescue SF-1 Deficiency for Steroidogenesis: An in vitro and in vivo Study %U https://karger.figshare.com/articles/dataset/Supplementary_Material_for_LRH-1_May_Rescue_SF-1_Deficiency_for_Steroidogenesis_An_in_vitro_b_b_and_in_vivo_b_b_Study/5127889 %R 10.6084/m9.figshare.5127889.v1 %2 https://ndownloader.figshare.com/files/8715811 %K LHR-1 %K NR5A1 mutations %K SF-1 deficiency %K Steroidogenesis %X Steroidogenic factor 1 (NR5A1/SF-1) mutations usually manifest in 46,XY individuals with variable degrees of disordered sex development and in 46,XX women with ovarian insufficiency. So far, there is no genotype-phenotype correlation. The broad spectrum of phenotype with NR5A1 mutations may be due to a second hit in a gene with similar function to NR5A1/SF-1. Liver receptor homologue-1 (LRH-1/NR5A2) might be a good candidate. We performed in vitro studies for the interplay between SF-1, LRH-1 and DAX-1, expression profiles in human steroidogenic tissues, and NR5A2 genetic studies in a cohort (11 patients, 8 relatives, 11 families) harboring heterozygote NR5A1/SF-1 mutations. LRH-1 isoforms transactivate the CYP17A1 and HSD3B2 promoters similarly to SF-1 and compensate for SF-1 deficiency. DAX-1 inhibits SF-1- and LRH-1-mediated transactivation. LRH-1 is found expressed in human adult and fetal adrenals and testes. However, no NR5A2/LRH-1 mutations were detected in 14 individuals with heterozygote NR5A1/SF-1 mutations. These findings demonstrate that in vitro LRH-1 can act like SF-1 and compensate for its deficiency. Expression of LRH-1 in fetal testis suggests a role in male gonadal development. However, as we found no NR5A2/LRH-1 mutations, the ‘second genetic hit' in SF-1 patients explaining the broad phenotypic variability remains elusive. %I Karger Publishers