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PMID: 15123806 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Paracrine regulation of mammalian oocyte maturation and male germ cell survival.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 19 ·2004-05-11 ·Pages 7323-8

Kawamura K, Kumagai J, Sudo S, Chun SY, Pisarska M, Morita H, Toppari J, Fu P, Wade JD, Bathgate RA, Hsueh AJ

Abstract

Mammalian oocytes are arrested at the prophase of meiosis before induction of maturation by the preovulatory luteinizing hormone (LH) surge. LH also promotes the survival of meiotic male germ cells in the testis. Because LH binds somatic cells, the mechanism underlying its regulation of germ cell function is unclear. We found that LH stimulates Leydig insulin-like 3 (INSL3) transcripts in ovarian theca and testicular Leydig cells. INSL3, in turn, binds a G protein-coupled receptor, LGR8 (leucine-rich repeat-containing G protein-coupled receptor 8), expressed in germ cells to activate the inhibitory G protein, thus leading to decreases in cAMP production. Treatment with INSL3 initiates meiotic progression of arrested oocytes in preovulatory follicles in vitro and in vivo and suppresses male germ cell apoptosis in vivo, thus demonstrating the importance of the INSL3-LGR8 paracrine system in mediating gonadotropin actions.

MeSH Terms
Animals Cell Survival/physiology Cyclic AMP/biosynthesis Insulin Luteinizing Hormone/physiology Male Oocytes/cytology Protein Binding Proteins/genetics,metabolism RNA, Messenger/genetics Rats Receptors, G-Protein-Coupled Receptors, Peptide/metabolism Spermatozoa/cytology
Chemicals
Insulin Leydig insulin-like protein Proteins RNA, Messenger Receptors, G-Protein-Coupled Receptors, Peptide relaxin receptors Luteinizing Hormone Cyclic AMP
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Kawamura Kazuhiro
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305-5317, USA.
Kumagai Jin
Sudo Satoko
Chun Sang-Young
Pisarska Margareta
Morita Hiroki
Toppari Jorma
Fu Ping
Wade John D
Bathgate Ross A D
Hsueh Aaron J W
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0307061101
Published
2004-05-11
Epub
2004-00-03
Pages
7323-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC409917
Subset
IM
Grants
NICHD NIH HHS · R01 HD044130 · United States
NICHD NIH HHS · HD 44130 · United States
External Links
PubMed source DOI: 10.1073/pnas.0307061101 PMC Full Text View journal details
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