alvocidib and Ovarian-Hyperstimulation-Syndrome

The corpus luteum is a dynamic endocrine structure with periodic development and regression during menstrual cycles. Its lifespan can be prolonged by human chorionic gonadotropin (hCG). However, the signal mechanisms of this phenomenon remain unclear.. Our objective was to investigate the molecular mechanisms of hCG in the maintenance of the viability of granulosa-lutein cells.. Granulosa-lutein cells were obtained from women undergoing in vitro fertilization. We examined the effects of hCG on the survival of cultured granulosa-lutein cells. The signal pathway inducing antiapoptotic protein was investigated.. hCG enhanced viability of granulosa-lutein cells through antiapoptosis but not proliferation, because the apoptotic marker of annexin V was decreased, but the proliferative markers of Ki67 and proliferating cell nuclear antigen were not increased. Myeloid cell leukemia-1 (Mcl-1) protein, but not B-cell lymphoma protein-2 or B-cell lymphoma protein-xL, was significantly induced by hCG and LH. The granulosa-lutein cells secreted vascular endothelial growth factor that induced endothelial permeability. Mcl-1 small interfering RNA increased DNA fragmentation and diminished the antiapoptotic effect of hCG. hCG induced Mcl-1 expression through the LH/hCG receptor, adenylate cyclase, protein kinase A, and cAMP response element-binding protein signal pathway. Flavopiridol inhibited Mcl-1 production, released cytochrome c, and induced apoptosis of granulosa-lutein cells.. We first demonstrate that hCG prevents apoptosis of granulosa-lutein cells through the induction of Mcl-1 protein via the LH/hCG receptor and a cAMP response element-binding protein-dependent pathway. We may have found the molecular mechanism for luteal rescue during early pregnancy. Mcl-1 prevents apoptosis and increases cell viability but not proliferation as mechanisms for luteal rescue. Mcl-1 is a key molecule of hCG signaling.

Topics: Analysis of Variance; Apoptosis; Blotting, Western; Cell Proliferation; Cell Survival; Cells, Cultured; Chorionic Gonadotropin; Corpus Luteum; Dose-Response Relationship, Drug; Female; Flavonoids; Humans; Immunoenzyme Techniques; Immunohistochemistry; Luteal Cells; Myeloid Cell Leukemia Sequence 1 Protein; Ovarian Hyperstimulation Syndrome; Piperidines; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-bcl-2; Receptors, LH; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering; Signal Transduction; Up-Regulation