Yadav, Vijay K and Medhamurthy, R (2002) Developmental Regulation of Mitogen-Activated Protein (MAP Kinases in Corpus Luteum: Changes during Luteolysis and Simulated Early Pregnancy in the Bonnet Monkey. In: ENDO 2002 (84th Annual Meeting), June 19 - 22, 2002, San Francisco, California, USA, P2-415.
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The process of luteinization, during which granulosa cells are transformed into luteal cells, is accompanied by dramatic changes in the response of luteal cells to LH. In primates, luteinization is accompanied by the loss of CREB expression and therefore, loss of a critical survival signaling cascade. Since MAP kinases are recognized to regulate cellular responses both through the phosphorylation of transcription factors, and through the phosphorylation of downstream target protein kinases, we investigated developmental regulation of MAP kinase activities and their role during luteolysis and rescue of the primate corpus luteum (CL). Corpora lutea (n=3) during different stages of the luteal phase (early, mid and late) were subjected to western blot analysis using antibodies specific to phospho- or total- form of the MAP kinases (ERK/p38/JNK). All three MAP kinase activities appeared to be maximal during the mid-luteal phase of the CL (50-100% higher compared to early and late phase), coincident with the maximal steroidogenesis (based on high StAR protein and serum P4 levels), indicating that MAP kinases possibly regulate survival and/or death of CL. Moreover, we investigated the role played by the MAP kinases during different functional status of the CL by employing two approaches. First, luteolysis was induced during the mid-luteal phase by an GnRH antagonist (Cetrorelix; 150mg/kg/day) and CL (n=4/time point) collected at 0, 12, 24 and 48 h of treatment. There was a precipitous fall in steroidogenesis (P4-2.13± 0.6 vs. 0.43±0.0 ng/ml at 0 and 48h; p<0.05). Western blot analysis of the CL lysates for MAP kinases revealed a significant (p<0.05) decrease in the pp38 and pERK1/2 levels (~70% decrease over control) 24-48 h after treatment, but not in the pJNK-1/2 and total MAP kinase levels. Suppression of the p38 and ERK levels during luteolysis suggest that these are required for the survival of the primate CL. Second, to address the role of p38 and ERK in the rescue of CL, we simulated early pregnancy by exogenous administration of hCG during days 5-9, 9-14 and 5-14 of the luteal phase. Analysis of tissues for MAP kinases revealed that pp38 levels were higher (~1.5 fold) only when the treatment was initiated on Day 9. Taken together, these findings suggest a possible involvement of MAP kinases during CL development, and a role for p38 in the survival of the CL in the primate.
|Item Type:||Conference Paper|
|Keywords:||Corpus luteum; Mitogen-activated protein kinase (MAPK); Gonadotropin-releasing hormone antagonist|
|Department/Centre:||Division of Biological Sciences > Molecular Reproduction, Development & Genetics (formed by the merger of DBGL and CRBME)|
|Date Deposited:||04 Sep 2004|
|Last Modified:||16 Jan 2013 11:40|
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