Developmental defects of the ventromedial hypothalamic nucleus and pituitary gonadotroph in the Ftz‐F1 disrupted mice
Koh Shinoda,Hong Lei,Hironori Yoshii,Masatoshi Nomura,Mamoru Nagano,Hiroharu Shiba,Hiroshi Sasaki,Yoshio Osawa,Yasuharu Ninomiya,Ohtsura Niwa,Ken Ichirou Morohashi,En Li +11 more
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TLDR
In this paper, double immunostaining of the pituitary for Ad4BP and trophic peptide hor- mones, FSH, TSH, and ACTH, indicated a re-stricted localization of the transcription factor to the gonadotroph.Abstract:
Ad4BP (or SF-1) has been iden- tified as a transcription factor which regulates all the steroidogenic P450 genes in the peripheral or- gans, and is encoded by the mammalian homo- logue of Drosophila FTZ-F1 gene. mRNA coding for Ad4BP was detected in the hypothalamus and pituitary of rats by RT-PCR. Immunohistochemi- cal analyses using an antiserum to Ad4BP in the brain and pituitary revealed that the transcrip- tion factor is expressed in nuclei of the dorso- medial part of the ventromedial hypothalamus (dmVMH) and in some subpopulation of the ade- nohypophysial cells. Double immunostaining of the pituitary for Ad4BP and trophic peptide hor- mones, FSH, TSH, and ACTH, indicated a re- stricted localization of Ad4BP to the gonadotroph. Disruption of the mouse Ftz-FI gene was clarified to induce severe defects in the organization of the dmVMH and the function of the pituitary gona- dotroph. However, some of the dm VMH neurons and pituitary gonadotrophs persisted, which pro- vided a sharp contrast to complete agenesis of the peripheral steroidogenic tissues (adrenal and go- nads) in the mutant mouse. Additional abnormal- ities were seen in the ventrolateral part of VMH and dorsomedial hypothalamic nucleus, both of which do not express Ad4BP but have strong reciprocal fiber-connections with the dmVMH. Aromatase P450-containing cells in the medial preoptico-amygdaloid region, which were devoid of Ad4BP, persisted even in the brain of the gene disrupted mice. The present results clearly showed that the hypothalamic and pituitary Ad4BPs are essential to normal development of the functional VMH and gonadotroph through some mechanism distinct from that in the periph-read more
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Nonsteroid nuclear receptors: What Are genetic studies telling us about their role in real life?
TL;DR: Together with some nuclear receptor mutations associated with pathological conditions, knockouts have led to significant advances in the authors' knowledge of the physiological functions of several nuclear receptors, but have also raised unexpected problems.
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Orphan nuclear receptors: from gene to function.
TL;DR: I. Nuclear Receptors: General Concepts and Orphans in Search of a Home.
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Steroidogenic Factor 1: A Key Determinant of Endocrine Development and Function
TL;DR: The initial Identification of SF-1 as a Key Determinant of Steroid Hormone Biosynthesis and its role in Vivo: Targeted Gene Disruption to Create SF- 1 Knockout Mice is identified.
Journal ArticleDOI
Wilms' Tumor 1 and Dax-1 Modulate the Orphan Nuclear Receptor SF-1 in Sex-Specific Gene Expression
Mark W. Nachtigal,Yoshifumi Hirokawa,Debra Enyeart-VanHouten,John N. Flanagan,Gary D. Hammer,Holly A. Ingraham +5 more
TL;DR: WT1 -KTS isoforms associate and synergize with SF-1 to promote MIS expression and it is proposed that WT1 and Dax-1 functionally oppose each other in testis development by modulatingSF-1-mediated transactivation.
Journal ArticleDOI
Sex Determination and Gonadal Development in Mammals
TL;DR: The growing body of knowledge relating to testis development and the beginnings of a picture of ovary development together illustrate the complex mechanisms by which these organ systems develop, inform the etiology, diagnosis, and management of disorders of sexual development, and help define what it is to be male or female.
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