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)

Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) play an important role in the development and maintenance of male and female gonads. Both these hormones act through the same specific receptor LH/hCG receptor (LHR). Recent studies have shown the existence of functional LHR in several non-gonadal tissues. The aim of this study was to confirm the functional existence of LHR in an endometrial adenocarcinoma cell line, Ishikawa cells, which has been used since long as an in vitro uterine endometrium model. Reverse transcriptase-polymerase chain reaction (RT-PCR) data showed the stable expression of LHR in this cell line. However, the receptor failed to activate the PKA pathway in response to hCG, which is the most conventional mode of LH/hCG action in target tissues. When tested for other pathways, hCG failed to activate them either. Nested RT-PCR confirmed the existence of full-length LHR and this was further supported by Western blot. This study demonstrated that although Ishikawa cells do possess a full-length LHR, which was confirmed by RT-PCR, nested RT-PCR, Western blot and DNA sequencing, it failed to activate the conventional LH-mediated downstream signaling. Based on these data we hypothesize that in Ishikawa cells LH/hCG does not utilize its conventional receptor. Whether it acts through some other receptor is a question, which can be answered through future research.
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PMID:Assessment of luteinizing hormone receptor function in an endometrial cancer cell line, Ishikawa cells in response to human chorionic gonadotrophin (hCG). 1754 47

The cDNA and genomic DNA of zebrafish (Danio rerio) protein kinase Cmu (PKCmu), with its promoter region, were obtained. The 508-amino acid zebrafish PKCmu has 86.17% similarity to human PKCmu. Real-time reverse-transcription polymerase chain reaction analysis with starvation and hormonal treatment found significant differences between the control group and the experimental group after 14 days of starvation. After injecting insulin-like growth factor II (IGF-II), growth hormone (GH), insulin, or human chorionic gonadotropin, significant differences were observed between the control and experimental groups 24 h after treatment. After injecting the gonadotropin-releasing hormone or luteotropin-releasing hormone, significant differences were seen between the control and experimental groups 15 h after treatment. These results suggest that in vivo PKCmu expression is regulated by the insulin family or by the GH, but other sex hormones produced a significant expression level more quickly than the insulin family and GH. The zebrafish PKCmu gene is located on zebrafish chromosome 17 and consists of 16 exons. A 2.6 kilobase pair on the 5' flanking region displayed maximal promoter activity in the zebrafish liver (ZFL) cell line after treatment with IGF-I, IGF-II, and GH. However, a 1.6 kilobase pair on the 5' flanking region displayed maximal promoter activity in the HeLa cell line after treatment with IGF-I, IGF-II, and GH. Finally, PKCmu may have important nuclear effects on cell growth and may involve nuclear localization. By transiently transfecting ZFL cells with various zebrafish PKCmu segments, we identified a nuclear localization signal: the amino acid sequence between amino acids 206 and 209 was able to predominantly direct enhanced green fluorescence protein (EGFP) into the nucleus, whereas a deletion of this motif abrogated the nuclear localization property.
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PMID:Cloning and expression analysis of a protein kinase C gene, PKCmu, and its regulation of the promoter region in zebrafish. 1757 Jul 65

Human chorionic gonadotropin (hCG) is a placental glycoprotein, mainly secreted by trophoblasts during pregnancy. Its function in endocrine regulation has been well documented, but its immunological role is still largely unclear. For a successful pregnancy, an effective innate immunity is needed to protect the mother and fetus against infection, while maintaining tolerance against the paternal antigens of the fetus. The aim of this study was to investigate the effect of hCG on the function of macrophages (Mvarphi), which are major players in the innate response. hCG treatment of IFN-gamma-primed Mvarphi resulted in increased production of NO, reactive oxygen species, IL-6 and IL-12p40, and enhanced phagocytosis of apoptotic cells. hCG treatment did not affect the induction of allogeneic T cell proliferation by IFN-gamma-primed Mvarphi. The observed effects were receptor-mediated and involved the protein kinase A signaling pathway, as indicated by blocking studies using specific inhibitors. In vivo thioglycollate-elicited Mvarphi also exhibited increased phagocytic ability upon IFN-gamma activation and hCG treatment. In conclusion, hCG enhances Mvarphi functions involved in innate immunity, while the capacity to stimulate allogeneic T cells remains unchanged.
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PMID:Chorionic gonadotropin can enhance innate immunity by stimulating macrophage function. 1762 51

ACTH has been shown to stimulate androgen production by the fetal/neonatal mouse testis through the melanocortin type 2 receptor (MC2R). This study was designed to localize the expression of MC2R in the neonatal mouse testis and characterize the effects of ACTH on testicular androgen production. Using immunohistochemistry, MC2R was localized to the fetal-type Leydig cell population of the neonatal testis. ACTH caused a time-dependent increase in cyclic AMP (cAMP) and testosterone production by isolated cells with an increase in cAMP apparent in < 3 min. There was no additive effect of maximally stimulating doses of ACTH and human chorionic gonadotropin (hCG). Androgen production in response to ACTH and hCG was reduced by UO126 and dexamethasone, which are the inhibitors of ERK1/2 and phospholipase A2 respectively. Expression of mRNA encoding StAR was increased fourfold by both ACTH and hCG, although expression of mRNA encoding for steroidogenic enzymes was not markedly affected. The potency of N-terminal fragments of ACTH to stimulate androgen production was similar to that seen previously in the adrenal. Data indicate that both LH and ACTH, acting through their respective receptors, stimulate steroidogenesis by fetal-type Leydig cells via arachidonic acid, protein kinase A, and ERK1/2 activation of StAR.
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PMID:Effects of ACTH and expression of the melanocortin-2 receptor in the neonatal mouse testis. 1763 72

It is well known that pregnancy is associated with fat weight gain. However, the mechanisms whereby fat mass accumulation is controlled during this period are poorly understood. Therefore, we attempted to determine whether human chorionic gonadotropin (HCG), in vitro, influences human adipose tissue development and/or metabolism. For the first time, HCG/LH receptor was characterized in human adipose cells. We also demonstrated that physiological concentrations of HCG, while unaltering both lipolysis and expression of two markers of lipogenesis (FAS and ADD1) in human mature adipocytes, stimulate human preadipocyte growth via the activation of a protein kinase A-independent mitogen-activated protein kinase/c-fos signaling pathway. HCG also moderately increases the preadipocyte differentiation capacity as reflected by enhanced glycerophosphate dehydrogenase activity and expression of key adipogenic transcriptional factors (C/enhancer-binding protein alpha and peroxisome proliferator-activated receptor gamma 2). Finally, HCG significantly stimulates the secretion of the pro-adipogenic factor, leptin, from human adipose tissue. Taken altogether, these data suggest that the pro-adipogenic effect of HCG in human preadipocytes contributes to explain why increased fat storage occurs during the first trimester of pregnancy.
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PMID:In vitro effects of chorionic gonadotropin hormone on human adipose development. 1764 Dec 81

Human chorionic gonadotropin (hCG) and LH play an important role in reproductive physiology. Both hCG and LH bind to the same LH/choriogonadotropin receptor (LH/CG-R). Recent reports documented the temporal and spatial expression of LH/CG-R in the developing and mature mammalian brain. Administration of hCG promoted nerve regeneration in vivo and neurite outgrowth and survival of primary neurons in vitro. The function of hCG/LH and LH/CG-R in the nervous system remains unclear. In this study, we report that hCG/LH induced distinct morphological and biochemical changes, characteristic of neuronal differentiation, in PC12 cells stably expressing LH/CG-R and that the differentiation effect is ligand dose and time dependent. Western blot analysis revealed that both the ERKs and p38 MAPK are activated after hCG treatment. Inhibitor studies showed both the ERK and p38 MAPK signal transduction pathways are required for this differentiation process, which is cAMP dependent and protein kinase A independent. These findings imply a potential role for hCG/LH and LH/CG-R in the development, maintenance, and regeneration of the mammalian nervous system, and in the neuropathogenesis of genetic diseases caused by a mutated LH/CG-R.
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PMID:Human chorionic gonadotropin induces neuronal differentiation of PC12 cells through activation of stably expressed lutropin/choriogonadotropin receptor. 1776 63

Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf.) has been used as a traditional Chinese medicine for dysfunction of the endocrine system. However, there have been few studies on the effects of adlay seed on the endocrine system. In the present study, both the in vivo and in vitro effects of methanolic extracts of adlay hull (AHM) on progesterone synthesis were studied. AHM was partitioned with four different solvents: water, 1-butanol, ethyl acetate, and n-hexane. Four fractions, namely, AHM-Wa (water fraction), AHM-Bu (1-butanol fraction), AHM-EA (ethyl acetate fraction), and AHM-Hex (n-hexane fraction), were respectively obtained. Granulosa cells (GCs) were prepared from pregnant mare serum gonadotropin-primed immature female rats and were challenged with different reagents, including human chorionic gonadotropin (hCG; 0.5 IU/ml), 8-bromo-adenosine-3',5'-cyclic monophosphate (8-Br-cAMP; 0.1 mM), forskolin (10 microM), 25-OH-cholesterol (10 microM), and pregnenolone (10 microM), in the presence or absence of AHM (100 microg/ml). The functions of steroidogenic enzymes, including protein expression of the steroidogenic acute regulatory protein (StAR), cytochrome P450 side chain cleavage enzyme (P450scc), protein kinase A (PKA), and aromatase activity, were investigated. The expression of StAR mRNA was also explored by using real-time reverse transcription-polymerase chain reaction. In the in vivo study, AHM decreased plasma progesterone and estradiol levels after an intravenous injection of AHM (2 mg/ ml/kg). In the in vitro studies, AHM decreased progesterone and estradiol via inhibition of (i) the cAMP-PKA signal transduction pathway, (ii) cAMP accumulation, (iii) P450scc and 3beta-HSD enzyme activities, (iv) PKA, P450scc and StAR protein expressions and StAR mRNA expression, and (v) aromatase activity in rat GCs. These results suggest that AHM decreased the production of progesterone via mechanisms involving the inhibition of the cAMP pathway, enzyme activities, and the protein expressions of P450scc and StAR in rat GCs.
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PMID:Effects of adlay (Coix lachryma-jobi L. var. ma-yuen Stapf.) hull extracts on the secretion of progesterone and estradiol in vivo and in vitro. 1789 26

NR4A1, also called NGFI-B in the rat, Nur77 in the mouse and TR3 in humans, belongs to the orphan nuclear steroid hormone receptor superfamily and is one of the immediate-early genes. In the endocrine organs, including the gonads, NGFI-B/Nur77 gene expression is rapidly induced by pituitary hormones. NGFI-B/Nur77 expression was found to be rapidly reduced by an estrogenic endocrine disrupter, diethylstilbestrol (DES) in theca interna cells of immature rat ovaries. DES treatment also triggered a rapid decrease of serum luteinizing hormone (LH) levels, suggesting that DES acts on the hypothalamo-pituitary axis to suppress LH secretion from the pituitary. The transcriptional regulation of NGFI-B/Nur77 by LH/human chorionic gonadotropin (hCG) or 8-bromoadenosine 3'-5'-cyclic monophosphate (8 Br-cAMP) was examined in mouse Leydig tumor cells MA-10. Luciferase assays using NGFI-B/Nur77 promoter constructs and electric mobility shift assays (EMSA) showed that NGFI-B/Nur77 gene expression was mediated through three of the four activator protein-1 (AP-1)-like sites, namely the -233 AP-1, -213 AP-1 and -69 AP-1 sites adjacent to the transcription start site of the NGFI-B/Nur77 promoter. We also demonstrated here that both the Jun family and cAMP-responsive element binding (CREB) proteins bind to the -233 AP-1 site, whereas the main binding protein to the -213 AP-1 site was CREB, and Jun family protein to the -69 AP-1 site, respectively. The rapid induction of NGFI-B/Nur77 gene expression by LH/hCG in MA-10 cells appears to be mediated by both CREB and Jun family proteins through the cAMP-protein kinase A (PKA) pathway.
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PMID:Regulation of NGFI-B/Nur77 gene expression in the rat ovary and in leydig tumor cells MA-10. 1816 34

The effects of salmon calcitonin (sCT) on the secretion of 17beta-estradiol (E(2)) were examined in female common carp, Cyprinus carpio. Vitellogenic stage fish adapted to high-Ca water were i.p. injected with vehicle, sCT, human chorionic gonadotropin (hCG), or hCG plus sCT. To determine whether ovarian follicles are equipped with CT receptors, a CT binding assay was conducted. In the in vitro experiments, vitellogenic follicles were incubated with stimulators and inhibitors. Administration of sCT increased the basal and hCG-stimulated E(2) release in vivo and in vitro. Binding characteristics of [(125)I]sCT to plasma membrane preparation of carp ovarian follicles showed saturability with high-affinity (K(d)=48.48 pmol/l and B(max)=1.2 pmol/mg protein). To clarify the mechanism of E(2) production by sCT, in vitro effect of sCT and hCG on aromatase activity (conversion of testosterone to E(2)) and cytochrome P450 aromatase (P450arom) gene expression in carp ovarian follicles were investigated. Salmon CT-stimulated both aromatase activity and P450arom gene expression in ovarian follicles of carp. sCT-stimulated E(2) release by the ovarian follicles in vitro was augmented in the presence of dibutyryl cAMP. Inhibitor of protein kinase A (PKA), SQ 22536 inhibited sCT-stimulated steroid production in a dose-dependent manner. Specific inhibitor of protein kinase C (PKC), NPC-15437 dihydrochloride had no inhibitory effects on sCT-induced E(2) release. The present study indicates that sCT binds specifically to carp ovary and stimulates E(2) production by increasing the activity of cytochrome P450 aromatase and P450arom gene expression. The results further suggest that stimulatory action of sCT on E(2) production is mediated through cAMP pathway.
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PMID:Stimulation of salmon calcitonin on secretion of 17beta-estradiol by the ovarian follicles of common carp, Cyprinus carpio. 1825 64

The actions of LH to induce ovulation and luteinization of preovulatory follicles are mediated principally by activation of cAMP-dependent protein kinase (PKA) in granulosa cells. PKA activity is targeted to specific locations in many cells by A kinase-anchoring proteins (AKAPs). We previously showed that FSH induces expression of microtubule-associated protein (MAP) 2D, an 80-kDa AKAP, in rat granulosa cells, and that MAP2D coimmunoprecipitates with PKA-regulatory subunits in these cells. Here we report a rapid and targeted dephosphorylation of MAP2D at Thr256/Thr259 after treatment with human chorionic gonadotropin, an LH receptor agonist. This event is mimicked by treatment with forskolin or a cAMP analog and is blocked by the PKA inhibitor myristoylated-PKI, indicating a role for cAMP and PKA signaling in phosphoregulation of granulosa cell MAP2D. Furthermore, we show that Thr256/Thr259 dephosphorylation is blocked by the protein phosphatase 2A (PP2A) inhibitor, okadaic acid, and demonstrate interactions between MAP2D and PP2A by coimmunoprecipitation and microcystin-agarose pull-down. We also show that MAP2D interacts with glycogen synthase kinase (GSK) 3beta and is phosphorylated at Thr256/Thr259 by this kinase in the basal state. Increased phosphorylation of GSK3beta at Ser9 and the PP2A B56delta subunit at Ser566 is observed after treatment with human chorionic gonadotropin and appears to result in LH receptor-mediated inhibition of GSK3beta and activation of PP2A, respectively. Taken together, these results show that the phosphorylation status of the AKAP MAP2D is acutely regulated by LH receptor-mediated modulation of kinase and phosphatase activities via PKA.
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PMID:Luteinizing hormone receptor activation in ovarian granulosa cells promotes protein kinase A-dependent dephosphorylation of microtubule-associated protein 2D. 1846 24


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