Its recep tor is comprised of two cytokine specific subunits and two signal transducing B subunits. Upon www.selleckchem.com/products/Lenalidomide.html binding, the GM CSF receptor complex is capable of stimulating proliferation, maturation and viability of hematopoietic and non hematopoietic cells. The interaction of GM CSF with its receptor stimulates multiple signal Inhibitors,Modulators,Libraries transduction pathways, including Jak STAT pathway, Ras Raf mitogen activated protein kinase pathway, phos phatidylinositol 3 kinase protein kinase B pathway, and protein kinase C pathway. GM CSF promote glucose uptake through PI 3 kinase PKB pathway via translocation of glucose transporter 1. GM CSF induction of the PKB Akt path way results in direct cell survival activity and inactivation of proapoptotic factors BAD, caspase 9 and forkhead.
Additionally, Akt promotes cell survival indirectly by regulating a number of processes involved in glucose metabolism. Both GM CSF and its receptor have been highly charac terized in the hematopoietic cell line, as well as Inhibitors,Modulators,Libraries in other cell types including fibroblasts, oligodendrocytes, tropho blast, endothelial and neoplastic. In reproductive tissues, GM CSF has been detected in testis, placenta, uterus, oviduct and ovary. GM CSF is expressed in utero by luminal and glandular epithelial cells and is subsequently secreted into the Inhibitors,Modulators,Libraries uterine lumen where activates neutrophils and macrophages during estrous cycle and early pregnancy. The GM CSF receptor has been detected from the fertilized oocyte through blastocysts stage in both mice and humans.
The se lective expression of GM CSF in theca, granulosa and lutheal cells coincides with peak follicular development, ovulation and luteinization. In mice, cumulus oocytes complexes express mRNA for the subunit of GM CSF receptor, which has been reported to facilitates glucose uptake and thereby promote Inhibitors,Modulators,Libraries viability and prolifera tion in certain cell Inhibitors,Modulators,Libraries lineages. Changes in estrogen and progesterone concentrations regulate the production of GM CSF which suggests a potential regulatory function during the estrus cycle. Thus, the expression of GM CSF in the mouse ovary and uterus and its steroidogenic regulation suggest an autocrine paracrine role in the ovarian physiology and embryonic development. Oogenesis relies on the highly coordinated interaction between the oocyte and surrounding cells. the oocyte reg ulates follicular cell proliferation and differentiation and follicular cells control oocyte meiotic arrest.
Inter action of cumulus with the oocyte provides local the following site produc tion of glycosaminoglycans, steroid hormones, nutrients and other factors that support oocyte maturation. Thereafter, presence of cumulus cells during IVF enhances fertilization and embryo development rates by facilitating sperm selection, capacitation, acrosome reaction and penetration.