Cloning and sequence analysis of the human gene encoding steroidogenic factor 1

Wong, MP; Ramayya, Meera S.; Chrousos, George P.; Driggers, Paul H.; Parker, Keith L.

doi:10.1677/jme.0.0170139

Cited by 100 publications

(66 citation statements)

References 21 publications

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“…The sequence of the human gene encoding SF-1 closely resembled that of the mouse gene (Oba et al, 1996;Wong et al, 1996) and SF-1 expression during human embryological development closely paralleled that in mice (Hanley et al, 1999;de Santa Barbara et al, 2000). Thus, it was plausible that mutations in the human SF-1 gene on chromosome 9q33 (Taketo et al, 1995) might cause endocrine disease.…”

Section: B Sf-1 and Human Diseasementioning

confidence: 93%

Steroidogenic Factor 1: an Essential Mediator of Endocrine Development

Parker

Rice

Lala

et al. 2002

Recent Progress in Hormone Research

334

203

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The orphan nuclear receptor steroidogenic factor 1 (SF-1, also called Ad4BP and officially designated NR5A1) has emerged as an essential regulator of endocrine development and function. Initially identified as a tissue-specific transcriptional regulator of the cytochrome P450 steroid hydroxylases, SF-1 has considerably broader roles, as evidenced from studies in knockout mice lacking SF-1. The SF-1-knockout mice lacked adrenal glands and gonads and therefore died from adrenal insufficiency within the first week after birth. In addition, SF-1 knockout mice exhibited male-to-female sex reversal of their internal and external genitalia, impaired expression of multiple markers of pituitary gonadotropes, and agenesis of the ventromedial hypothalamic nucleus (VMH). These studies delineated essential roles of SF-1 in regulating endocrine differentiation and function at multiple levels, particularly with respect to reproduction. This chapter will review the experiments that established SF-1 as a pivotal, global determinant of endocrine differentiation and function. We next discuss recent insights into the mechanisms controlling the expression and function of SF-1 as well as the current status of research aimed at delineating its roles in specific tissues. Finally, we highlight areas where additional studies are needed to expand our understanding of SF-1 action. I. Initial Isolation of Steroidogenic Factor 1Steroid hormones are essential for fluid and electrolyte balance, intermediary metabolism, sexual differentiation, and reproductive function. Once the pathways of steroid hormone biosynthesis were defined and shown to involve the concerted actions of several cytochrome P450 mixed-function oxidases, attention turned to elucidating the mechanisms that regulate the expression of these enzymes. With the isolation of the bovine 21-hydroxylase cDNA (White et al., 1984b), followed shortly thereafter by the cloning of cDNAs encoding the side-chain cleavage enzyme (Matteson et al., 1984;Morohashi et al., 1984) and 11␤-hydroxylase (John et al., 1984), these questions could be addressed at a molecular level.

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Section: B Sf-1 and Human Diseasementioning

confidence: 93%

Steroidogenic Factor 1: an Essential Mediator of Endocrine Development

Parker

Rice

Lala

et al. 2002

Recent Progress in Hormone Research

334

203

View full text Add to dashboard Cite

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“…pcDNA.hSF1 (pcDNA3.1/Zeo(C), Invitrogen) containing human SF1 cDNA was used to generate expression vectors carrying either the p.R84C mutation or the previously described p.G146A polymorphism (20,21). The QuikChange Site-Directed Mutagenesis Kit (Stratagene, La Jolla, CA, USA) was used to introduce a c.C250T mutation (designated p.R84C SF1) or a c.G437C mutation (designated p.G146A SF1).…”

Section: Plasmidsmentioning

confidence: 99%

A novel mutation in the accessory DNA-binding domain of human steroidogenic factor 1 causes XY gonadal dysgenesis without adrenal insufficiency

Reuter¹,

Goji²,

Bingham³

et al. 2007

eur j endocrinol

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Objective: Steroidogenic factor 1 (SF1), officially designated NR5A1, is a nuclear receptor that plays key roles in endocrine development and function. Previous reports of human SF1 mutations revealed a spectrum of phenotypes affecting adrenal function and/or gonadal development and sex differentiation. We present the clinical phenotype and functional effects of a novel SF1 mutation. Patient: The patient is a 22-year-old 46, XY Japanese patient who presented with dysgenetic testes, atrophic vasa deferentia and epididymides, lack of Mü llerian structures, and clitoromegaly. Endocrine studies revealed normal adrenal function. Results: Analysis of the SF1 gene revealed compound heterozygosity for a previously described p.G146A polymorphism and a novel missense mutation (p.R84C) in the accessory DNA-binding domain. The father carried the p.G146A polymorphism and the mother had the p.R84C mutation; both were clinically and reproductively normal. Functional studies demonstrated that the p.R84C SF1 had normal nuclear localization but decreased DNA-binding affinity and transcriptional activity compared with wild-type SF1; it did not exhibit any dominant negative activity. Conclusions: These results describe the human phenotype that results from compound heterozygosity of the p.G146A polymorphism and a novel p.R84C mutation of SF1, thereby extending the spectrum of human SF1 mutations that impair testis development and sex differentiation in a sex-limited manner while preserving normal adrenal function. 157 233-238 European Journal of Endocrinology

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“…The human NR5A1 gene is mapped to the long arm of chromosome 9 (9q33, Figure 1) and consists of 7 exons spanning approximately 27 Kb of genomic DNA (Taketo et al, 1995;Oba et al, 1996;Wong et al, 1996). Exon 1 is untranslated.…”

Section: Transcriptionmentioning

confidence: 99%