Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 53 patients, 24 healthy pregnant women and 29 patients with EPH (edema, proteinuria, hypertension) syndrome, the intravenous phenolsulphonphthalein test was performed between the 32nd and 42 weeks of pregnancy. At the same time, the serum creatinine and estrogen excretion in the 24 hour urine were determined. According to this, normal pregnancy and also pregnancies with one or more symptoms of the EPH syndrome without raised blood pressure do not cause changes of the PSP plasma level. A statistically significant rise in the PSP plasma level is only found with a blood pressure of 140/90 mm Hg, and simultaneously a close correlation to the estrogen excretion in the urine (r = -0.4) and the blood pressure (r = 0.6). Estrogen excretion is reduced with increasing blood pressure (r = -0.75). No correlation could be established between the PSP serum level and the creatinine in the serum.
...
PMID:[Investigations of changes in the phenolsulphonphthalein plasma levels in pregnant women with EPH syndrome (author's transl)]. 80 10

Gonadectomized male and female rats were treated with equimolar doses of estradiol benzoate (EB) or testosterone pripionate (TP) daily for one week and enzyme activities were measured in the basomedial hypothalamus, corticomedial amygdala, and pituitary. In females, the hypothalamus showed estrogen-dependent increases in glucose-6-phosphate dehydrogenase (G6PDH), isocitrate dehydrogenase (ICDH), and malate dehydrogenase (MDH). Activities of ICDH and MDH were elevated in the amygdala. In the pituitary, estrogen administration resulted in increased levels of G6PDH, 6-phosphogluconate dehydrogenase (6PGDH), and lactic dehydrogenase (LDH). The estrogen antagonist, MER-25, effectively blocked estrogen-dependent increases in pituitary G6PDH and 6PGDH. Administration of TP did not result in changed enzyme levels. In males, treatment with EB and TP resulted in significant elevations in some but not all enzymes that were increased by EB in the female. Estrogen-dependent increases of activity in males were noted in pituitary G6PDH, 6PGDH, and LDH, in hypothalamic MDH, and in amygdaloid ICDH. Administration of TP led to increased levels of pituitary G6PDH, 6PGDH, LDH, ICDH, and MDH, hypothalamic ICDH and G6PDH, and amygdaloid MDH. The pattern of enzyme changes found in male and female brain and pituitary is discussed in relation to behavioral responses to gonadal hormones, nuclear uptake of gonadal hormones, and metabolism of androgen.
...
PMID:Effect of gonadal hormones on enzyme activities in brain and pituitary of male and female rats. 111 98

The aim of this study was to investigate the effects of estradiol and tamoxifen (TAM) on the growth of human endometrial carcinomas in athymic mice. Tissues from primary tumors were implanted into estradiol-treated mice. In passage 2, animals were treated with (a) placebo, (b) estradiol, (c) estradiol plus TAM, and (d) TAM alone. The size of the tumors was measured weekly. Estrogen receptors (ER) were determined with the dextran-coated charcoal method and/or ER enzyme-linked immunoassay. Progesterone receptors were measured with the dextran-coated charcoal technique. Of 16 primary tumors, 2 grew in the athymic mice and were studied further. Tumor EL was positive for ER (145 fmol/mg protein) and progesterone receptors (993 fmol/mg protein). Tumor EL in passage 2 was not significantly stimulated by estradiol, but was stimulated by a combination of estradiol and TAM. Treatments (estradiol, estradiol plus TAM, or TAM) all increased tumor growth in passage 3. Tumor BR and a metastasis BR-MET were ER and progesterone receptor negative, applying dextran-coated charcoal, ER enzyme-linked immunoassay, and immunocytochemistry. The BR and BR-MET cells contain the complete ER gene but do not express any measurable amounts of ER mRNA as quantitated by Northern blot analysis, using a complete ER complementary DNA probe. In all animal passages the growth rate was significantly higher in estradiol-treated mice compared with the control. TAM alone had some growth stimulatory effect, but much smaller than observed in the estradiol group. TAM inhibited estradiol-stimulated growth. These results suggest that estradiol and possibly TAM are capable of stimulating tumor growth in the athymic mice independently from ER, potentially through a host-mediated mechanism.
...
PMID:Enhanced growth of an estrogen receptor-negative endometrial adenocarcinoma by estradiol in athymic mice. 275 9

The present study determined if the decline in placental progesterone (P4) production that results from administration of the antiestrogen ethamoxytriphetol (MER-25) to pregnant baboons results from a change in placental low density lipoprotein (LDL) uptake and/or degradation. Pregnant baboons (Papio anubis) were untreated (n = 10) or received MER-25 (25 mg/kg BW, orally; n = 10) daily on days 140-170 of gestation (term, 184 days). Placentas were removed by cesarean section on day 170 of gestation, and villous tissue was dispersed with 0.1% collagenase at 37 C for 40 min. Placental cells (10(6)) were incubated in medium 199 (pH 7.2) for 12 h at 37 C with increasing amounts (5-100 micrograms) of [125I]LDL, with or without a 100-fold excess of unlabeled baboon LDL. Mean (+/- SE) peripheral serum P4 concentrations on days 140-170 of gestation were 51% lower (P less than 0.01) in MER-25-treated (5.7 +/- 0.3 ng/ml) than in untreated (11.6 +/- 0.5 ng/ml) baboons. The uptake of LDL was 56% lower (P less than 0.01) in placental cells from antiestrogen-treated (6.3 +/- 1.6 ng/micrograms cell protein) than in those from untreated (14.4 +/- 1.9 ng/micrograms cell protein) baboons. The dissociation constants for placental LDL uptake, as assessed by Scatchard analysis, however, were similar in untreated (0.80 microgram/ml) and MER-25-treated (0.76 microgram/ml) animals. The amount of [125I]LDL concomitantly degraded by cells from baboons that received MER-25 was 54% of that degraded by cells from untreated controls. The relative decline in LDL degradation by cells of antiestrogen-treated baboons was proportionate to the decline in overall LDL uptake. The results indicate, therefore, that antiestrogen treatment decreased the amount of placental LDL uptake, but did not change the affinity for the lipoprotein. We suggest that the decline in placental P4 production elicited in pregnant baboons by antiestrogen results, at least in part, from subnormal LDL uptake. We propose that one of the mechanisms by which estrogen regulates the biosynthesis of P4 by the placenta during baboon pregnancy is by increasing receptor-mediated placental cell uptake of cholesterol in the form of LDL. Estrogen, therefore, may regulate LDL uptake by the placenta and thus the availability of cholesterol for P4 biosynthesis via the LDL pathway.
...
PMID:Effect of the antiestrogen ethamoxytriphetol (MER-25) on placental low density lipoprotein uptake and degradation in baboons. 335 75

Rat skeletal muscle cytosol proteins bound 3H-diethylstilbestrol (3H-DES). More than 90% of this binding was high capacity and low affinity. Serum albumin accounted for roughly 50-60% of the binding, as evidenced by its precipitation with anti-rat albumin IgG. About half of the binding was distinguishable from albumin and other serum proteins by its precipitation in 40% saturated ammonium sulfate. This material sedimented at 4-5S in high-salt sucrose gradients, and resolved into two components (8S and 4-5S) in low-salt. Following incubation at 23-27 degree C for one hour, 2% of the bound 3H-DES in whole cytosol (approximately 2 fmole/Mg cytosol protein) was retained by DNA cellulose, and was eluted with 0.6 M KCl. This small fraction of the total binding was inhibited by estrogens and DES analogues: estradiol-17 beta, DES, dienestrol, and hexestrol were strong inhibitors; isodienestrol, dimethylstilbestrol, estradiol-17 alpha, estrone, tamoxifen, MER-25, CI-628, and nafoxidine were weak inhibitors; dihydrotestosterone, testosterone, and prednisone did not compete. These observations indicate that specific estrogen-binding sites exist in rat skeletal muscle.
...
PMID:Specific cytosol binding of diethylstilbestrol in rat skeletal muscle. 675 12

These studies were designed to investigate the role of estrogen on progesterone production in early pregnancy in the baboon, when the contribution of the corpus luteum and placenta has not been established. Oral administration of the estrogen antagonist MER-25 at two dosage levels (15 and 30 mg/kg/day) to the pregnant baboon from days 35 to 55 after conception results in a decline in peripheral plasma levels of progesterone within a few days and persists for at least 20 days after the termination of treatment with no effect on plasma estradiol levels. The same study was done with the use of a different estrogen antagonist, trioxifene mesylate (5 mg/kg/day), and there was no effect on plasma progesterone, although a transient depression in plasma estradiol was evident. These actions may be due to an inherent estrogenicity of trioxifene. In preliminary studies an effect of these estrogen antagonists on placental size and morphology has been observed. Estrogen deprivation in early pregnancy of the baboon results in a depression in plasma progesterone and indicates a placental requirement for estrogen in progesterone product at this stage of pregnancy.
...
PMID:The effect of estrogen antagonism on progesterone production in early pregnancy in the baboon (Papio cynocephalus). 682 61

Investigations were made in 312 healthy gravidas, from 20 to 40 weeks of gestation, in order to establish normal values of serum and urinary estrogens. The study also included 210 gravidas with EPH gestosis classified into three groups according to symptomatology: mild EPH gestosis (98), moderate EPH gestosis (70), and severe EPH gestosis (42). Mild cases did not show any significant deviations from normal serum and urinary estrogen values. Moderate cases were found to have serum estrogen values considerably below the urinary values, and with significant deviations from the normal values. Extremely low values of serum and urinary estrogens were found in severe EPH gestoses. These pregnancies ended unfavourably. Estrogen levels in every form of EPH gestosis reflect the functional state of the feto-placental unit and the degree of fetal risk within this integrated system.
...
PMID:[Enzyme immunoassay measurement of estrogens in EPH gestoses (author's transl)]. 734 20

Antagonists of steroid hormones are clinically important in the management of breast cancer. However, the duration of response is limited due to the development of hormone-independent tumors in virtually all cases. In an attempt to obtain insight into the mechanisms underlying antiestrogen resistance, the consequences of epigenetic changes in gene expression were studied in vitro. Estrogen-dependent ZR-75-1 human breast cancer cells were treated with 5-azacytidine, an inhibitor of DNA methylation, and cultured in the absence of estradiol or in the presence of antiestrogens. Estrogen-independent cell colonies developed within 3 weeks at high frequency in 5-azacytidine-treated cultures (0.7 x 10(-3), in contrast to control cultures (< or = 10(-8). The derived cells (ZR/AZA) were resistant to 4-hydroxytamoxifen and ICI 164,384, independent of the selection protocol, but had lost the ability to grow anchorage-independent. Whereas expression of estrogen receptor, progesterone receptor, and pS2 were down-regulated, expression of epidermal growth factor (EGF) receptor and HER2/neu were increased in ZR/AZA cells. In contrast to the stable altered expression patterns of estrogen receptor and EGF receptor, transient keratin 7 expression was observed. Transforming growth factor-alpha mRNA was identified in ZR-75-1 cells and ZR/AZA cells and EGF-like peptides were secreted in the culture medium. Proliferation of ZR/AZA cells could be partially inhibited with an EGF receptor-blocking antibody. Presence of both growth factor receptors and possible ligands suggests the development of an autocrine growth mechanism. Our data show that epigenetic alterations of gene expression result in rapid progression of breast cancer cells to hormone independence.
...
PMID:Induction of estrogen independence of ZR-75-1 human breast cancer cells by epigenetic alterations. 753 60

Estrogen replacement therapy is effective in the prevention of postmenopausal osteoporosis, and a direct action of 17-beta-estradiol (17 beta E2) on osteoblastic and osteoclastic cells has been demonstrated. The inhibition of bone resorption by ipriflavone (IP), an isoflavone derivative devoid of estrogenic properties but active in potentiating the effects of estrogen on bone tissue, has been shown in in vitro and in vivo studies and confirmed by clinical data. To investigate the molecular mechanisms that underlie IP effect, we studied the possible interactions of IP and its four main in vivo metabolites (I, II, III, and V) with the estrogen receptor (ER) in the human preosteoclastic cell line FLG 29.1, whose growth and function are modulated by the compound. In parallel experiments, the human breast cancer cell line MCF7 was also analyzed. IP binding sites were demonstrated in the nuclear fraction of FLG 29.1 cells. 17 beta E2 and other steroid compounds failed to displace IP binding to intact FLG 29.1 cells. Similarly, IP and metabolites I, III, and V were not able to displace 17 beta E2 binding to intact MCF7 cells, whereas metabolite II showed an IC50 of 61 nM. 17 beta E2 binding to FLG 29.1 cells was increased after preincubation with metabolites I, III, and V. IP and its metabolites did not induce ER-dependent gene expression in FLG 29.1 and MCF7 cells transfected with a reporter gene and an estrogen response element (ERE).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Interactions between ipriflavone and the estrogen receptor. 773 26

The developing ovarian follicle is one of the most rapidly proliferating normal tissues in vivo. Mesenchymal-epithelial cell interactions between theca cells and granulosa cells are essential for this follicular expansion. Ovarian hormones (i.e. estrogen and LH) may promote follicular development by regulating the local production of mesenchymal inducer proteins that mediate theca cell-granulosa cell interactions. Recently, theca cells were shown to produce keratinocyte growth factor (KGF) that can act in a paracrine manner to stimulate granulosa cell growth. In this study, the developmental and hormonal regulation of KGF was examined during follicular development in the bovine ovary. Expression of KGF in theca cells and the KGF receptor (KGFR, or splice variant of the fibroblast growth factor family receptor family, FGFR-2) in granulosa cells was examined using RT-PCR. Both KGF and KGFR were detected throughout follicular development in small (<5 mm), medium (5-10 mm), and large (>10 mm) follicles. Quantitative RT-PCR assays were used to determine steady-state levels of KGF and KGFR messenger RNAs. Developmental regulation of KGF and KGFR was analyzed in freshly isolated theca cells and granulosa cells from small, medium, and large follicles. Observations demonstrated that expression of KGF (in theca cells) and KGFR (in granulosa cells) was highest in large follicles. These results suggest that KGF actions are important for the rapid proliferation of granulosa cells in large follicles. Estrogen and LH are the primary endocrine hormones that regulate theca cell function in vivo. Therefore, hormonal regulation of KGF was analyzed by treating serum-free theca cell cultures with estrogen and human CG (hCG, an LH agonist). Results showed that both estrogen and hCG stimulated KGF gene expression in theca cells. These results suggest that estrogen and LH may promote follicular growth (i.e. granulosa cell proliferation), in part, by stimulating the local production of KGF. Effects of KGF on granulosa cell differentiated functions were examined. Treatment with KGF reduced basal levels and FSH-stimulated levels of aromatase activity in bovine and rat granulosa cells. In addition, KGF inhibited the ability of hCG to stimulate progesterone production by granulosa cells. The inhibition of granulosa cell steroid production by KGF was likely the indirect effect of promoting cellular proliferation. Therefore, KGF directly stimulates granulosa cell proliferation and indirectly inhibits granulosa cell differentiated functions. Combined results suggest that theca cell production of KGF may be important for ovarian folliculogenesis. This is the first report of the regulation of KGF expression in the ovary. The developmental and hormonal regulation of KGF and KGFR during folliculogenesis provides evidence that KGF may be important for hormone-induced granulosa cell proliferation. As a result, KGF may be essential for establishing the microenvironment required for oocyte maturation in the ovary.
...
PMID:Developmental and hormonal regulation of keratinocyte growth factor expression and action in the ovarian follicle. 942 19


1 2 3 4 5 6 7 8 9 10 Next >>

---