Abstract
The nuclear receptor steroidogenic factor 1 (SF-1) regulates the biosynthesis of the two essential mediators of male sexual differentiation, androgens and Müllerian-inhibiting substance, and is required for adrenal and gonadal development and gonadotropin expression. SF-1 is also expressed in the embryonic ventral diencephalon, subsequently localizing to the ventromedial hypothalamic nucleus, a region important for reproductive behavior. Mice lacking SF-1 secondary to targeted disruption of the Ftz-F1 gene had normal numbers and location of GnRH neurons but exhibited grossly impaired ventromedial hypothalamic nucleus structure. Despite their apparently normal GnRH neurons, treatment of Ftz-F1-disrupted mice with GnRH restored pituitary gonadotropin expression. These studies define SF-1's essential role within a discrete hypothalamic nucleus previously linked to reproduction.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Movement
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology*
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Female
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Fushi Tarazu Transcription Factors
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Gene Expression Regulation, Developmental*
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Gonadotropin-Releasing Hormone / biosynthesis
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Gonadotropin-Releasing Hormone / genetics
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Gonadotropin-Releasing Hormone / therapeutic use
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Gonadotropins, Pituitary / biosynthesis
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Gonadotropins, Pituitary / genetics
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Homeodomain Proteins
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Hypothalamo-Hypophyseal System / physiopathology*
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Male
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Mice
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Mice, Knockout
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Neurons / metabolism
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Neurons / ultrastructure
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Receptors, Cytoplasmic and Nuclear
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Receptors, LHRH / biosynthesis
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Receptors, LHRH / genetics
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Sex Differentiation / genetics
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Steroidogenic Factor 1
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Transcription Factors / deficiency
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription Factors / physiology*
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Ventromedial Hypothalamic Nucleus / embryology*
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Ventromedial Hypothalamic Nucleus / growth & development
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Ventromedial Hypothalamic Nucleus / metabolism
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Ventromedial Hypothalamic Nucleus / pathology
Substances
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DNA-Binding Proteins
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Fushi Tarazu Transcription Factors
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Gonadotropins, Pituitary
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Homeodomain Proteins
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Receptors, Cytoplasmic and Nuclear
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Receptors, LHRH
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Steroidogenic Factor 1
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Transcription Factors
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steroidogenic factor 1, mouse
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Gonadotropin-Releasing Hormone