Article

Steroidogenic factor 1 (SF-1) is essential for endocrine development and function.

Department of Internal Medicine and Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
The Journal of Steroid Biochemistry and Molecular Biology (Impact Factor: 3.98). 69(1-6):13-8.
Source: PubMed

ABSTRACT Steroidogenic factor 1 (SF-1), an orphan nuclear receptor, initially was isolated as a key regulator of the tissue-specific expression of the cytochrome P450 steroid hydroxylases. Thereafter, analyses of sites of SF-1 expression during mouse embryological development hinted at considerably expanded roles for SF-1, roles that were strikingly confirmed through the analyses of SF-1 knockout mice. These SF-1 knockout mice exhibited adrenal and gonadal agenesis, associated with male-to-female sex reversal of their internal and external genitalia and death from adrenocortical insufficiency. These findings showed unequivocally that SF-1 is essential for the embryonic survival of the primary steroidogenic organs. SF-1 knockout mice also had impaired pituitary expression of gonadotropins and agenesis of the ventromedial hypothalamic nucleus (VMH), establishing that SF-1 regulates reproductive function at all three levels of the hypothalamic-pituitary gonadal axis. This article reviews the experiments that have defined these essential roles of SF-1 in endocrine development and highlights important areas for future studies.

0 Bookmarks
 · 
72 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The link between cholesterol homeostasis and male fertility has been clearly suggested in patients who suffer from hyperlipidemia and metabolic syndrome. This has been confirmed by the generation of several transgenic mouse models or in animals fed with high cholesterol diet. Next to the alteration of the endocrine signaling pathways through steroid receptors (androgen and estrogen receptors); "orphan" and "adopted" nuclear receptors, such as the Liver X Receptors (LXRs), the Proliferating Peroxisomal Activated Receptors (PPARs) or the Liver Receptor Homolog-1 (LRH-1), have been involved in this cross-talk. These transcription factors show distinct expression patterns in the male genital tract, explaining the large panel of phenotypes observed in transgenic male mice and highlighting the importance of lipid homesostasis and the complexity of the molecular pathways involved. Increasing our knowledge of the roles of these nuclear receptors in male germ cell differentiation could help in proposing new approaches to either treat infertile men or define new strategies for contraception.
    Molecular and Cellular Endocrinology 07/2012; · 4.04 Impact Factor
  • Reviews in Endocrine and Metabolic Disorders 07/2001; 2(3):275-287. · 4.58 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Summary Motivation: Development of methods for search for transcription factor binding sites (TFBSs) is important for investigation of regulatory regions in eukaryotic genes. The accuracy of currently used methods is insufficient for correct recognition of binding sites of a given transcription factor (TF) or a group of factors of a single family, class, etc. Results: We propose a new approach to search for TFBSs by the example of five site types: SRE, PPRE, HNF4, COUP-TF, and SF-1. The approach involves partitioning the regions including TFBSs into local regions and selection of the most suitable dinucleotides for each of the regions. Cross-validation tests of the functions of TFBS recognition allowed division of the sites into two groups which agree with the structure-functional subdivision of these TFs into two superclasses: (1) Basic Domains and (2) Zinc-coordinating DNA-binding domains. Availability: The program for site recognition is included into the GeneExpress system; section "RegScan", http://wwwmgs.bionet.nsc.ru/mgs/programs/sitega/.