Activation of the lutropin/choriogonadotropin receptor inhibits apoptosis of immature Leydig cells in primary culture.
We used proliferating primary cultures of immature rat Leydig cells expressing the recombinant human LH/choriogonadotropin (CG) receptor (LHR) to test the hypothesis that activation of this receptor inhibits apoptosis. We also compared the effects of LH/CG with epidermal growth factor (EGF) and IGF-I because these have been previously shown to stimulate proliferation and/or inhibit apoptosis in Leydig cells. Human CG (hCG), EGF, and IGF-I stimulated the phosphorylation of ERK1/2 and Akt in primary cultures of immature rat Leydig cells. These three hormones also robustly stimulated thymidine incorporation and inhibited drug-induced apoptosis. Using selective inhibitors of ERK1/2 (UO126) or Akt phosphorylation (LY294002), we show that the ERK1/2 and Akt cascades are both involved in the hCG- and EGF-dependent proliferation of Leydig cells, but only the ERK1/2 cascade is involved in their antiapoptotic actions. The same strategy showed that the proliferative and antiapoptotic actions of IGF-I are mediated entirely by the Akt pathway. These results show that activation of the LHR inhibits apoptosis in Leydig cells and that it does so through stimulation of the ERK1/2 pathway.
Tai
Ping
P
Department of Pharmacology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242, USA.
Shiraishi
Koji
K
Ascoli
Mario
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000494:pharmacology*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D012102:Reproductive Control Agents / Q000494:pharmacology*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
C412373:AG 1879; D002070:Butadienes; D006063:Chorionic Gonadotropin; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D009570:Nitriles; D011743:Pyrimidines; D012102:Reproductive Control Agents; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3