Document Detail


Distinct roles for steroidogenic factor 1 and desert hedgehog pathways in fetal and adult Leydig cell development.
MedLine Citation:
PMID:  17495005     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Testicular Leydig cells produce testosterone and provide the hormonal environment required for male virilization and spermatogenesis. In utero, fetal Leydig cells (FLCs) are necessary for the development of the Wolffian duct and male external genitalia. Steroidogenic factor 1 (Sf1) is a transcriptional regulator of hormone biosynthesis genes, thus serving a central role in the Leydig cell. Desert hedgehog (Dhh), a Sertoli cell product, specifies the FLC lineage in the primordial gonad through a paracrine signaling mechanism. Postnatally, FLCs are replaced in the testis by morphologically distinct adult Leydig cells (ALCs). To study a putative interaction between Sf1 and Dhh, we crossed Sf1 heterozygous mutant mice with Dhh homozygous null mice to test the function of these two genes in vivo. All of the compound Sf1(+/-); Dhh(-/-) mutants failed to masculinize and were externally female. However, embryonic gonads contained anastomotic testis cords with Sertoli cells and germ cells, indicating that sex reversal was not attributable to a fate switch of the early gonad. Instead, external feminization was attributable to the absence of differentiated FLCs in XY compound mutant mice. ALCs also failed to develop, suggesting either a dependence of ALCs on the prenatal establishment of Leydig cell precursors or that Sf1 and Dhh are both required for ALC maturation. In summary, this study provides genetic evidence that combinatorial expression of the paracrine factor Dhh and nuclear transcription factor Sf1 is required for Leydig cell development.
Authors:
Susan Y Park; Minghan Tong; J Larry Jameson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-05-10
Journal Detail:
Title:  Endocrinology     Volume:  148     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-07-19     Completed Date:  2007-09-11     Revised Date:  2009-08-11    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3704-10     Citation Subset:  AIM; IM    
Affiliation:
Division of Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Mullerian Hormone
Cholesterol Side-Chain Cleavage Enzyme / metabolism
Female
Gene Expression Regulation, Developmental / physiology
Germ Cells / cytology,  physiology
Glycoproteins / metabolism
Hedgehog Proteins / genetics,  metabolism*
Homeodomain Proteins / genetics,  metabolism*
Leydig Cells / cytology,  physiology*
Male
Mesonephros / embryology,  physiology
Mice
Mice, Inbred Strains
Mice, Mutant Strains
Mitosis
Pregnancy
Receptors, Cytoplasmic and Nuclear / genetics,  metabolism*
Sex Differentiation / physiology
Sex Reversal, Gonadal
Steroidogenic Factor 1
Testicular Hormones / metabolism
Testis / cytology,  embryology*,  physiology*
Transcription Factors / genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
R01HD044801/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Glycoproteins; 0/Hedgehog Proteins; 0/Homeodomain Proteins; 0/Receptors, Cytoplasmic and Nuclear; 0/Steroidogenic Factor 1; 0/Testicular Hormones; 0/Transcription Factors; 0/steroidogenic factor 1, mouse; 80497-65-0/Anti-Mullerian Hormone; EC 1.14.15.6/Cholesterol Side-Chain Cleavage Enzyme

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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