Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pituitary, a master gland of neuroendocrine system, secretes hormones that orchestrate many physiological processes, under the regulation of multiple signaling pathways. To investigate the genes involved in hormones expression of human pituitary, homemade cDNA microarray containing 14,800 human genes/ESTs were used to profile the gene expression in both fetal and adult pituitaries. Seven hundred and twelve known genes changed over 2-fold between the both tissues. Of which, 23 genes were changed with hormones expression in aging were confirmed by RT-PCR, not only the known regulators such as Pit1, GATA4, ESRRA, GABA-A, and EMK, but also LOC55884, DUSP3, PNN, and RCL, which had not been reported to be involved in the hormones expression. Correspondingly, the mRNAs of GH, PRL, POMC, TSH-beta, FSH-beta, and LH-beta, was increased as much as 6- to 20-fold in adult pituitary than those in fetal pituitary, by real-time quantitative RT-PCR assay. In addition, the mRNAs of signaling pathways, such as cAMP-PKA-CREB, PI3K-Akt, and PKA-ERK were further investigated. Of them, it was only cAMP-PKA-CREB pathway, but not PI3K-Akt and PKA-ERK have the same expressing pattern as hormones. It suggested that cDNA microarray is highly advantages to profile the differential expressed genes that were involved in hormones expression of human pituitary, but it might ignore some responding proteins regulated posttranscriptionally.
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PMID:cDNA microarray reveals signaling pathways involved in hormones expression of human pituitary. 1589 16

GnRH applied continuously or in pulses of high frequency increases follistatin, and thereby differentially regulates FSH and LH. This study was conducted in alphaT3-1 and LbetaT2 gonadotroph cells to begin to understand the signaling pathways through which GnRH stimulates follistatin synthesis. GnRH increased follistatin expression and stimulated a follistatin-LUC reporter in LbetaT2 cells, but was inactive in alphaT3-1 cells. GnRH also increased cAMP levels and stimulated a cAMP-responsive promoter only in LbetaT2 cells. Forskolin stimulated follistatin in both cell lines. GnRH activation of follistatin was blocked by the PKA inhibitor H89 and by over-expression of a dominant-negative inhibitor of CREB (A-CREB). Activation was also suppressed by PKC depletion, and was reduced by the PKC inhibitor bisindolylmaleimide. The MEK inhibitor PD98059 blocked activation by GnRH or forskolin implying that MAPK contributes to cAMP/PKA-mediated activation of follistatin. When LbetaT2 cells were transfected with follistatin-LUC together with A-CREB, and perifused with GnRH, activation was blocked during continuous GnRH, but stimulation by hourly GnRH pulses was unaffected. These experiments provide evidence that GnRH stimulates follistatin through multiple signaling pathways, and that cAMP-CREB activation is obligatory when GnRH is applied continuously. The finding that follistatin transcription was CREB-dependent with continuous but not pulsatile GnRH implies that the mode of ligand activation of GnRH receptors modifies the transcriptional response by changing the signaling network. These results provide a mechanism linking GnRH pulsatility to the differential control of FSH-beta and LH-beta gene expression through follistatin.
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PMID:Transcriptional regulation of follistatin expression by GnRH in mouse gonadotroph cell lines: evidence for a role for cAMP signaling. 1748 56

There is increasing evidence for communication among pituitary cells. Hormone-producing pituitary cells may communicate with each other and with folliculostellate cells. The latter cells surround pituitary hormone-producing cells and are connected by tight junctions to form a network that allows for their coordinated function. Folliculostellate cells are targets of cytokines, peptides, and steroid hormones, and produce growth factors and cytokines, including follistatin, the dynamic regulator of follicle-stimulating hormone (FSH) production that binds activin, and limits activin signaling. Pituitary adenylate cyclase-activating peptide (PACAP) and its receptor are found in folliculostellate cells in which they stimulate transcription of the follistatin gene through cyclic adenosine monophosphate/protein kinase A (PKA) signaling. When PACAP increases, follistatin levels increase, and FSH-beta mRNA is reduced. PACAP also activates gonadotrophs to stimulate transcription of the gonadotropin alpha-subunit gene and lengthen the LH-beta mRNA, presumably to prolong it half-life, and increases responsiveness to GnRH. Accordingly, PACAP differentially regulates FSH and LH, and may prove to be a key player in reproduction through a novel paracrine mechanism.
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PMID:Paracrine control of gonadotrophs. 1771 Jul 34