Paracrine regulation of mammalian oocyte maturation and male germ cell survival.
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.
Kawamura
Kazuhiro
K
Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305-5317, USA.
Kumagai
Jin
J
Sudo
Satoko
S
Chun
Sang-Young
SY
Pisarska
Margareta
M
Morita
Hiroki
H
Toppari
Jorma
J
Fu
Ping
P
Wade
John D
JD
Bathgate
Ross A D
RA
Hsueh
Aaron J W
AJ
D000818:Animals; D002470:Cell Survival / Q000502:physiology*; D000242:Cyclic AMP / Q000096:biosynthesis; D007328:Insulin; D007986:Luteinizing Hormone / Q000502:physiology; D008297:Male; D009865:Oocytes / Q000166:cytology*; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide / Q000378:metabolism; D013094:Spermatozoa / Q000166:cytology*
D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C033395:relaxin receptors; D007986:Luteinizing Hormone; D000242:Cyclic AMP