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Novel steroidogenic factor-1 homolog (ff1d) is coexpressed with anti-Mullerian hormone (AMH) in zebrafish.
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
2005 (English)In: Developmental Dynamics, ISSN 1058-8388, E-ISSN 1097-0177, Vol. 233, no 2, 595-604 p.Article in journal (Refereed) Published
Abstract [en]

ff1d is a novel zebrafish FTZ-F1 gene with sequence characteristics indicating similar basic regulatory mechanisms as the previously characterized ff1 based on the presence of an FTZ-F1 box in the DNA binding domain and an interactive domain (I-Box) and an AF-2 in the ligand binding domain. The highest sequence similarity was found between ff1d and ff1b (NR5A4), a gene previously shown to be a functional homolog to the steroidogenic factor 1 (SF-1). The expression pattern of ff1d was comparable to ff1b both in brain and gonads in adults and in the pituitary and interrenal cells in embryos. SF-1 is crucial in mammalian steroidogenesis and in sex determination by regulating the anti-Mullerian hormone (AMH). In fish, AMH has not been described previously. In this study, we cloned a partial zebrafish AMH. AMH was detected in growing oocytes, the ovarian follicular layer and testicular Sertoli cells, similar to the mammalian pattern, suggesting a conserved role between zebrafish and mammalian AMH. Teleosts lack a gene homolog to SRY, which constitute the universal testis-determining factor in mammalian sex determination. Comparison of sequences and expression patterns indicate that ff1d is a new candidate for sex determination and differentiation in a way similar to SF-1, possibly involving AMH.

Place, publisher, year, edition, pages
2005. Vol. 233, no 2, 595-604 p.
Keyword [en]
ff1d, NR5A, FTZ-F1, AMH, MIS, sex determination
National Category
Cell and Molecular Biology
URN: urn:nbn:se:umu:diva-4282DOI: 10.1002/dvdy.20335PubMedID: 15768398OAI: diva2:143302
Available from: 2004-11-19 Created: 2004-11-19 Last updated: 2010-06-23Bibliographically approved
In thesis
1. Developmental and reproductive regulation of NR5A genes in teleosts
Open this publication in new window or tab >>Developmental and reproductive regulation of NR5A genes in teleosts
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In mammals sex chromosomes direct and initiate the development of male and female gonads and subsequently secondary sex characteristics. In most vertebrates each individual is pre-destined to either become male or female. The process by which this genetic decision is carried out takes place during the embryonic development and involves a wide range of genes. The fushi tarazu factor-1 (FTZ-F1) is a nuclear receptor and transcription factor, which in mammals has proven to be essential for gonad development and directs the differentiation of testicular Sertoli cells. A mammalian FTZ-F1 homologue subtype, steroidogenic factor-1 (SF-1), is a member of the nuclear receptor 5A1 (NR5A1) group and regulate several enzymes involved in steroid hormone synthesis. It also regulates the expression of the gonadotropin releasing hormone receptor GnRHr and the β-subunit of the luteinizing hormone (LH), indicating that it functions at all levels of the reproductive axis. Another mammalian FTZ-F1 subtype, NR5A2, is in contrast to SF-1, not linked to steroidogenesis or sex determination. Rather, NR5A2 is involved in cholesterol metabolism and bile acid synthesis in liver. Hormones and environmental factors such as temperature and pH can influence teleost development and reproductive traits, rendering them vulnerable to pollutants and climate changes. Very little is known about teleost FTZ-F1 expression, regulation and function. In this thesis, expression patterns of four zebrafish FTZ-F1 genes (ff1a, b, c and d) and two Arctic char genes (acFF1α and β) were studied during development, displaying complex embryonic expression patterns. Ff1a expression was in part congruent with expression of both mammalian NR5A1 and NR5A2 genes but also displayed novel expression domains. The complexity of the expression pattern of ff1a led to the conclusion that the gene may be involved in several developmental processes, including gonad development, which also was indicated by its transcriptional regulation via Sox9a. Two ff1a homologues were also cloned in Arctic char and were shown to be involved in the reproductive cycle, as the expression displayed seasonal cyclicity and preceded that of the down stream steroidogenic genes StAR and CYP11A. High levels were correlated to elevated plasma levels of 11-ketotestosterone (11KT) in males and 17β-estradiol (E2) in females respectively. Treatment with 11KT did not affect FTZ-F1 expression directly but was indicated to alter expression of CYP11A and 3β-hydroxysteroid dehydrogenase. E2 treatment was indicated to down-regulate the expression of testicular FTZ-F1, which may contribute to the feminising effect previously observed in E2 treated salmonids. Ff1d is a novel FTZ-F1 gene, expressed in pituitary and interrenal cells during development, suggesting steroidogenic functions. In adult testis and ovary ff1d was co-expressed with anti-Mullerian hormone (AMH), a gene connected to sex determination in mammals and previously not characterised in teleost fish. The co-expression between ff1d and AMH was found in Sertoli and granulosa cells, which is congruent with the co-expression of mammalian SF-1 and AMH. This suggests that ff1d and AMH may have similar functions in teleost sex differentiation and reproduction, as their mammalian homologues. In conclusion, this study present data that connects members of the teleost FTZ-F1 family to reproduction, cholesterol metabolism and sex determination and differentiation.

Place, publisher, year, edition, pages
Umeå: Molekylärbiologi (Teknisk-naturvetenskaplig fakultet), 2004. 44 p.
Cell and molecular biology, FTZ-F1, NR5A, zebrafish, teleost, arctic char, SF-1, LRH-1, fushi tarazu, Cell- och molekylärbiologi
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Biology
urn:nbn:se:umu:diva-374 (URN)91-7305-779-7 (ISBN)
Public defence
2004-12-17, Major Groove, 6L, NUS, 90187, Umeå, 09:00
Available from: 2004-11-19 Created: 2004-11-19Bibliographically approved

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von Hofsten, Jonas
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