INSL3/Leydig Insulin-like Peptide Activates the LGR8 Receptor Important in Testis Descent
Several orphan G protein-coupled receptors homologous to gonadotropin and thyrotropin receptors have recently been identified and named as LGR4â8. INSL3, also known as Leydig insulin-like peptide or relaxin-like factor, is a relaxin family member expressed in testis Leydig cells and ovarian theca...
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Published in | The Journal of biological chemistry Vol. 277; no. 35; pp. 31283 - 31286 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
30.08.2002
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Subjects | |
Online Access | Get full text |
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Summary: | Several orphan G protein-coupled receptors homologous to gonadotropin and thyrotropin receptors have recently been identified
and named as LGR4â8. INSL3, also known as Leydig insulin-like peptide or relaxin-like factor, is a relaxin family member expressed
in testis Leydig cells and ovarian theca and luteal cells. Male mice mutant for INSL3 exhibit cryptorchidism or defects in
testis descent due to abnormal gubernaculum development whereas overexpression of INSL3 induces ovary descent in transgenic
females. Because transgenic mice missing the LGR8 gene are also cryptorchid, INSL3 was tested as the ligand for LGR8. Here,
we show that treatment with INSL3 stimulated cAMP production in cells expressing recombinant LGR8 but not LGR7. In addition,
interactions between INSL3 and LGR8 were demonstrated following ligand receptor cross-linking. Northern blot analysis indicated
that the LGR8 transcripts are expressed in gubernaculum whereas treatment of cultured gubernacular cells with INSL3 stimulated
cAMP production and thymidine incorporation. The present study identified the ligand for an orphan G protein-coupled receptor
based on common phenotypes of ligand and receptor null mice. Demonstration of INSL3 as the ligand for LGR8 facilitates understanding
of the mechanism of testis descent and allows studies on the role of INSL3 in gonadal and other physiological processes. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.C200398200 |