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Submitted on October 28, 2005
Accepted on January 5, 2006
Department of Molecular Reproduction, Development and Geneticsand Primate Research Laboratory, Indian Institute of Science, Bangalore -560012, India
* To whom correspondence should be addressed. E-mail: rmm{at}mrdg.iisc.ernet.in.
Changes in the MAPK activities were examined in the corpus luteum (CL) during luteolysis and pregnancy, employing GnRH antagonist (Cetrorelix)-induced luteolysis, stages of CL, and hCG treatment to mimic early pregnancy as model systems in the bonnet monkey. We hypothesized that MAP kinases could serve to phosphorylate critical phosphoproteins to regulate luteal function. Analysis of several indices for structural (caspase-3 activity and DNA fragmentation) and functional (P4 and StAR expression) changes in the CL revealed that the decreased luteal function observed during Cetrorelix treatment and late luteal phase was associated with increased caspase-3 activity and DNA fragmentation. As expected hCG treatment dramatically increased luteal function, but the indices for structural changes were only partially attenuated. All three MAP kinases appeared to be constitutively active in the mid luteal phase CL, and activities of ERK-1/2 and p38MAPK (p38), but not JNK-1/2, decreased significantly (P < 0.05) within 12-24 h following Cetrorelix treatment. During the late luteal phase, in contrast to decreased ERK-1/2 and p38 activities, JNK-1/2 activities increased significantly (P < 0.05). While hCG treatment increased ERK-1/2 and p38 activities, it decreased JNK-1/2 activities. The activation status of p38 was correlated with the phosphorylation status of an upstream activator, MAPK kinase-3/6 and the expression of MAPKAPK-3, a downstream target. Intraluteal administration of p38 kinase inhibitor (SB203580), but not MEK-1/2 inhibitor (PD98059), decreased the luteal function. Together, these data suggest an important role for p38 in the regulation of CL function in primates.
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