Abstract

Background Fushi tarazu factor 1 (FTZ-F1) encodes an orphan nuclear receptor belonging to the nuclear receptor family 5A (NR5A) which includes adrenal 4-binding protein or steroidogenic factor-1 (Ad4BP/SF-1) and liver receptor homologue 1 (LRH-1) and plays a pivotal role in the regulation of aromatases.Methodology/Principal FindingsPresent study was aimed to understand the importance of FTZ-F1 in relation to brain aromatase (cyp19a1b) during development, recrudescence and after human chorionic gonadotropin (hCG) induction. Initially, we cloned FTZ-F1 from the brain of air-breathing catfish, Clarias gariepinus through degenerate primer RT-PCR and RACE. Its sequence analysis revealed high homology with other NR5A1 group members Ad4BP/SF-1 and LRH-1, and also analogous to the spatial expression pattern of the latter. In order to draw functional correlation of cyp19a1b and FTZ-F1, we analyzed the expression pattern of the latter in brain during gonadal ontogeny, which revealed early expression during gonadal differentiation. The tissue distribution both at transcript and protein levels revealed its prominent expression in brain along with liver, kidney and testis. The expression pattern of brain FTZ-F1 during reproductive cycle and after hCG induction, in vivo was analogous to that of cyp19a1b shown in our earlier study indicating its involvement in recrudescence.Conclusions/SignificanceBased on our previous results on cyp19a1b and the present data, it is plausible to implicate potential roles for brain FTZ-F1 in ovarian differentiation and recrudescence process probably through regulation of cyp19a1b in teleosts. Nevertheless, these interactions would require primary coordinated response from ovarian aromatase and its related transcription factors.

Highlights

  • Fushi tarazu factor 1 (FTZ-F1) is an orphan nuclear receptor [1,2] that was initially identified as an activator of fushi tarazu, a pair-ruled homeobox gene involved in the segmentation of Drosophila [2]

  • Biosynthesis of steroid hormones is regulated by the tissue-specific expression of cytochrome P450 (CYP) enzymes [6] and analysis of the promoter motifs of CYP and steroid hydroxylase genes revealed the presence of elements specific for a transcription regulator, FTZ-F1 [7,8]

  • Phylogenetic analysis revealed that catfish FTZ-F1 is evolutionarily closer to the counterparts of channel catfish, Ictalurus punctatus and the Nile tilapia, Oreochromis niloticus (Ad4BP/steroidogenic factor-1 (SF-1)), and showed high homology with NR5A1 genes of most teleosts and other vertebrates (Fig. 2)

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Summary

Introduction

Fushi tarazu factor 1 (FTZ-F1) is an orphan nuclear receptor [1,2] that was initially identified as an activator of fushi tarazu, a pair-ruled homeobox gene involved in the segmentation of Drosophila [2]. FTZ-F1 constitutes a distinct subfamily, NR5A, in the superfamily of nuclear receptors [3] It includes two major subgroups of related genes with separate function and expression patterns in higher vertebrates. Ad4BP/SF-1, a homologue of FTZ-F1, has been identified as an important regulator of steroidogenesis due to its regulatory influence on several CYP enzymes involved in steroidogenic pathways [9]. This group of transcription factors is critical for normal physiological entrainment of hypothalamo-hypophyseal-gonadal axis during reproduction and sexual differentiation in vertebrates [10]. Fushi tarazu factor 1 (FTZ-F1) encodes an orphan nuclear receptor belonging to the nuclear receptor family 5A (NR5A) which includes adrenal 4-binding protein or steroidogenic factor-1 (Ad4BP/SF-1) and liver receptor homologue 1 (LRH-1) and plays a pivotal role in the regulation of aromatases

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