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Fushi tarazu factor-1 mRNA and protein is expressed in steroidogenic and cholesterol metabolising tissues during different life stages in Arctic char (Salvelinus alpinus)
Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
Umeå University, Faculty of Medicine, Molecular Biology.
Umeå University, Faculty of Medicine, Molecular Biology.
2003 (English)In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 132, no 1, 96-102 p.Article in journal (Refereed) Published
Abstract [en]

Fushi tarazu factor-1 (FTZ-F1) genes belong to the nuclear receptor family 5A (NR5A). The distribution pattern of NR5A genes in teleosts suggests that they control functions separate to, or in addition to, those of other vertebrates. In mammals NR5A1 genes, including steroidogenic factor-1 (SF-1), are primarily involved in steroidogenesis. NR5A2 contain the alpha-fetoprotein transcription factor (FTF) genes, which protect mammalian embryos against maternal estrogens, and are involved in cholesterol transfer and metabolism. In this study we have analysed the expression of two Arctic char FTZ-F1 forms belonging to the NR5A2 group. The expression starts during early development and the transcripts are present in embryonic liver/pancreas and gonadal regions. The genes are up-regulated during embryogenesis as the embryo develops towards hatch, as shown by increased mRNA and protein levels. In adult Arctic char the FTZ-F1 forms are primarily located to tissues involved in steroidogenesis as well as cholesterol metabolism. Thus, a division of NR5A into SF-1 (NR5A1) and FTF (NR5A2) specific functions does not appear to have occurred in teleosts.

Place, publisher, year, edition, pages
2003. Vol. 132, no 1, 96-102 p.
Keyword [en]
Fushi tarazu, FTZ-F1, SF-1, NR5A1, NR5A2, Arctic char, Development, Salmonid, Teleost
National Category
Cell and Molecular Biology
URN: urn:nbn:se:umu:diva-4280DOI: 10.1016/S0016-6480(03)00034-0PubMedID: 12765648OAI: diva2:143300
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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