Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Distribution within the brain of a 3-fold modified ACTH4-9 analog with a remarkably potentiated behavioral activity, 4-MET (O2), 8-d-Lys, 9-Phe-ACTH4-9, was investigated. The radioactive labeled [7-3H-Phe]ACTH4-9 analog was administered intraventricularly in urethane anesthetized rats in a dose of approximately 170 ng. Total radioactivity in CSF, measured in samples drawn from the cisterna magna, decreased over the period of 0.5-4 h after injection from 51 to 2% of the injected dose. Intraventricular injection of the ACTH4-9 analog resulted in high intact peptide levels in the brain. At 2 h after injection the distribution of radioactivity over 2500 micronm and 300 micronm frontal cut brain slices was rather homogenous. Data from distribution studies over topographically defined gross brain structures indicated that the septal area, which is involved in eliciting behavioral activities of ACTH-like neuropeptides, accumulated most of the injected radioactivity per gram wet weight. The distribution profiles within the brain of the [3H]ACTH4-9 analog and [3H]Phe showed considerable differences. Uptake studies in various brain nuclei after intraventricular administration of the [3H]ACTH4-9 analog demonstrated that the greatest part of the investigated nuclei exhibited relative low or medium uptake of radioactivity. This was also true for hippocampal and thalamic nuclei, which have been suggested as effected sites of action for ACTH peptides. Very high accumulation of radioactivity occurred only in the septal nuclei, particularly the dorsal and fimbrial septal nuclei. The results indicate selective uptake of the ACTH4-9 analog in the septal area, suggesting a possible significance of this area as a site of action of ACTH neuro-peptides.
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PMID:Distribution of a behaviorally highly potent ACTH4-9 analog in rat brain after intraventricular administration. 19 19

We studied reactivity of highly purified pituitary hormones in our human calcitonin (hCT) radioimmunoassay (RIA) which can detect 1 pg of hCT. ACTH at doses of greater than 1 microgram of peptide per RIA tube reacted in the hCT assay, as did beta-endorphin (beta EPH) at a dose of 10 micrograms per tube. No reactivity was observed with comparable concentrations of all other known pituitary hormones. ACTH also reacted at doses greater than 1 microgram per tube with 7 other hCT antisera which recognized differing antigenic determinants in the calcitonin molecule but it was not reactive with 2 antisera against porcine calcitonin or 2 antisera against salmon calcitonin. This slight degree of cross-reactivity of hACTH and beta EPH in the hCT RIA cannot account for the presence of immunoreactive CT in pituitary glands. Nevertheless, antisera used for the localization of peptides must be rigorously tested for the existence of cross-reactivities with other possible substances, especially if such antisera detect the peptide in unexpected tissues.
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PMID:Reactivity of ACTH and synthetic ACTH peptides with antisera to human calcitonin. 23 Feb 60

Normal sleep is associated to physiological nocturnal rises in Interleukin 1 beta (IL 1 beta) secretion. The 24 h pattern of IL 1 beta, beta-Endorphin (beta-EPH), ACTH and cortisol (F) production was evaluated in four male healthy volunteers. Two subjects were unable to sleep, due to the stress of the experiment; in these cases, no detectable plasma IL 1 beta secretion, both diurnal and nocturnal, was present, beta-EPH plasma levels were significantly higher (p < 0.01) than in the subjects who slept regularly and, in one case, increased F plasma levels were also reported. A strong negative correlation between IL 1 beta and beta-EPH plasma levels was present in all the cases. In conclusion, stress-induced sleep alterations might deeply affect both diurnal and nocturnal IL 1 beta plasma secretion, probably due to the hypothalamus-pituitary-adrenal axis (HPAA) activation, and beta-EPH might be the reliable marker of the stress-induced HPAA activation level.
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PMID:Interleukin-1 beta and beta-endorphin circadian rhythms are inversely related in normal and stress-altered sleep. 133 95

To better understand the sources and regulation of circulating inhibin during primate pregnancy, immunoreactive inhibin was measured in sera obtained from the maternal saphenous vein, uterine vein, and the fetus at varying times of baboon pregnancy. In both intact and fetectomized (fetus removed on day 100 of gestation; term = 184 days) animals, maternal serum inhibin concentrations were relatively constant between day 80 (first sampling day) and day 110 of gestation, after which they then steadily increased until days 155-165 (end of sampling). The increase in inhibin concentrations was significantly less in the fetectomized animals than in the intact baboons. Restoration of estrogen levels in the fetectomized animals did not significantly alter the circulating inhibin concentrations. Similarly, administration of the estrogen antagonist MER-25 to intact animals in the last trimester had no effect on maternal serum inhibin concentrations. Inhibin concentrations in uterine venous blood collected on day 100 of gestation were not significantly different from those in the maternal saphenous vein. However, the inhibin concentrations of uterine venous blood collected late in gestation (days 155-165) in either intact or fetectomized animals were significantly higher than the corresponding maternal venous concentrations, suggesting that the uteroplacental tissue becomes a source of circulating inhibin during the third trimester of pregnancy. Consistent with this suggestion was the detection of inhibin alpha-subunit mRNA in the placentae of intact or fetectomized animals obtained late in pregnancy, but its absence at midgestation. Immunoreactive inhibin concentrations were about 16 times higher (6500 +/- 831 mu Leq/mL) in fetal blood than in maternal blood (411 +/- 23 mu Leq/mL) at midgestation. The fetal blood concentrations significantly decreased to about 2800 mu Leq/mL by days 160-165 of gestation, but were still greater than those in the mother (approximately 1000 mu Leq/mL). The umbilical arterial and venous concentrations were the same as the fetal blood concentration of inhibin. The role of the baboon fetal adrenal in inhibin production was studied. Fetal adrenals collected from days 59, 135, and 167 of gestation contained the mRNA for the inhibin alpha-subunit in relatively high abundance. The in utero administration of ACTH for 30 min to five fetuses at midgestation (days 100-110) apparently did not alter the fetal concentration of immunoreactive inhibin. In summary, maternal serum inhibin levels increase during the last trimester of baboon pregnancy. This is suggested to be due to an increasing contribution of placental inhibin secretion, which is regulated not by placental estrogen production but, perhaps, by placental growth.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of immunoreactive inhibin patterns in baboon pregnancy: maternal, placental, and fetal considerations. 143 97

We have reported that ACTH stimulation of dehydroepiandrosterone (DHA) formation by the baboon fetal adrenal at midgestation was suppressed by estrogen. Because fetal adrenal regulation changes with advancing gestation, the action of estrogen on fetal adrenal steroidogenesis may also be dependent on the degree of fetal adrenal maturation. We examined this possibility in the present study by determining the effects of ACTH and estrogen on DHA formation by adrenal cells of fetuses obtained from baboons at mid- and late gestation and from animals administered the antiestrogen MER-25 throughout late gestation. Because low density lipoprotein (LDL) provides substrate for the fetal adrenal, we also determined whether the effect of estrogen was mediated by LDL uptake. Adrenals were removed from baboon fetuses on day 100 (midgestation; n = 7) and day 170 (late gestation; n = 6; term, day 184) of gestation from untreated animals and on day 170 from fetuses whose mothers were treated with MER-25 on days 140-170 (25 mg/kg BW.day; n = 7). Cells were dispersed with 0.2% collagenase and incubated at 37 C for 3 h in 4 ml medium 199 with 10 nM ACTH, 10(-6) M estradiol and/or 500 micrograms LDL. The secretion of DHA into medium was determined by RIA. At midgestation, mean (+/- SE) basal DHA formation (nanograms per 10(5) cells/3 h) was 5.8 +/- 2.1, and DHA was increased (P less than 0.01) by ACTH to 20.0 +/- 5.9. Although estradiol alone had no effect, estradiol prevented the increase in DHA obtained with ACTH. Basal DHA production by adrenals of late gestation (0.7 +/- 0.3 ng/10(5) cells) was lower (P less than 0.01) than at midgestation. ACTH increased (P less than 0.01) DHA in a comparable manner near term in the presence (2.0 +/- 0.4) or absence (1.7 +/- 0.4) of estradiol. Thus, in contrast to day 100, estrogen did not attenuate the action of ACTH on adrenal cells on day 170. In fetal adrenal cells obtained on day 170 from MER-25-treated baboons, DHA formation (1.4 +/- 0.6 ng/10(5) cells) was comparably increased (P less than 0.05) to 2.4 +/- 0.2 and 3.0 +/- 0.5 ng/10(5) cells by ACTH in the absence or presence of estradiol. Thus, ACTH remained effective in enhancing DHA by adrenal cells of fetuses exposed in utero to antiestrogen. DHA formation by adrenals of midgestation was increased (P less than 0.05) to 15.4 +/- 4.8 and 27.4 +/- 7.5 ng/10(5) cells, respectively, by LDL and ACTH plus LDL.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Modulation of adrenocorticotropin-stimulated baboon fetal adrenal dehydroepiandrosterone formation in vitro by estrogen at mid- and late gestation. 216 46

In sheep, the prepartum rise in fetal plasma cortisol (F) is associated with an increase in the corticosteroid-binding capacity (CBC) of the plasma. We examined whether CBC changed during preterm labor, induced by administering ACTH to the fetus, and we examined the role of F in such changes. Beginning on day 127, chronically catheterized fetal sheep were divided into six groups; 1) saline control infusions (n = 4); 2) pulsatile ACTH (P-ACTH; 66 ng/min for 15 min every 2 h; n = 5); 3) P-ACTH (as 2) plus metopirone (MET; 500 mg/24 h n = 5); 4) P-ACTH and MET (as 3) plus F (13.3 micrograms/min for 15 min every 2 h; n = 3); 5) P-ACTH and MET (as 3) plus F (133 micrograms/min for 15 min every 2 h; n = 4); 6) P-ACTH and MET (as 3) plus dexamethasone (0.56 micrograms/min for 15 min every 2 h for 50 h, then 5.6 micrograms/min for 15 min every 2 h until 100 h; n = 4). All infusions continued for 100 h. Fetal blood samples were collected at 8-h intervals for determination of plasma F concentration and CBC. Estrone and progesterone were measured in 8-h samples of maternal femoral arterial blood. P-ACTH resulted in a significant increase in CBC within 24 h; values at 72-96 h were 2- to 3-fold greater than controls. Rises in CBC were positively correlated with the changes in plasma F in the P-ACTH-treated fetuses and preceded changes in plasma progesterone or estrogens. MET treatment prevented the P-ACTH-induced increases in F and CBC. Exogenous F and dexamethasone overcame the MET-induced inhibition of P-ACTH-induced increases in CBC. We conclude that in fetal sheep 1) CBC is elevated by P-ACTH treatment; and 2) F may mediate this stimulation of its own binding protein.
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PMID:Possible role of cortisol in the stimulation of cortisol-binding capacity in the plasma of fetal sheep. 298 75

The present study demonstrates the presence of the endogenous opioid peptides, beta-endorphin (beta-EP) and methionine-enkephalin (MET-ENK), and of ACTH in cell homogenates and interstitial fluid from sternal biopsy of leukemic children. The peptides were identified by chromatography and radioimmunoassay. In leukemic children with lymphoblastic cells present in the sternal sample, concentrations of immunoreactive (ir) beta-EP in the cell homogenate, but not in the fluid, were significantly higher than in leukemic children with normal bone marrow. In contrast, ir MET-ENK and ir ACTH did not differ between the two study groups either in the cell homogenate or in the fluid. These data suggest the presence of a complex system of opioid peptides in the cells and interstitial fluid of bone marrow of leukemic children with the highest concentrations of ir beta-EP appearing in samples collected during the active phase of the disease, and may suggest a possible role of opioid peptides as immunomodulatory substances.
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PMID:Changes in immunoreactive beta-endorphin, methionine-enkephalin and ACTH in bone marrow cells and fluid from leukemic children. 302 64

The objective of this study was to determine whether anti-oestrogens (nafoxidine, MER-25) would block the suppressive effects of ACTH on gonadotrophin secretion in immature rats. Female rats were castrated at 25-26 days of age, and an Alzet osmotic minipump containing ACTH (1-24) or saline was implanted in each animal. ACTH was administered at a rate of 1 IU/day by constant infusion. Beginning on the day of surgery, animals were injected daily for 5 days with 0.25, 5 or 25 micrograms/100 g body weight of nafoxidine or 5 mg MER-25 and sacrificed on the sixth day following castration. ACTH lowered serum LH concentrations and increased pituitary LH levels. Serum androstenedione concentrations were more than two times greater in ACTH-infused than in control rats, but serum oestrone levels were not affected. Serum testosterone and oestradiol concentrations in ACTH-infused rats remained below levels of detection. Administration of 0.25 micrograms of nafoxidine prevented the suppressive effects of ACTH on serum LH. Serum levels of LH in these animals were comparable to saline-treated controls (418 +/- 94 vs 443 +/- 73 ng/ml). The two higher doses of nafoxidine and MER-25 were ineffective in suppressing the actions of ACTH on serum LH. MER-25 reduced serum LH values in both controls and ACTH-infused rats. Serum FSH concentrations were not altered by ACTH or nafoxidine treatment. MER-25 elevated pituitary FSH concentrations in both control and ACTH-infused rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of anti-oestrogens on gonadotrophin secretion in control and ACTH-infused immature rats. 632 94

Mice were treated with [MET(O2)4, D-Lys8,Phe9]ACTH4-9 (ORG 2766, 100 micrograms/kg per day SC) for 10 days. On the tenth day mice were injected with [3H]2-deoxyglucose and its cerebral accumulation determined in 17 brain areas. The combined results of four experiments indicated a significant decrease of the 2-deoxyglucose accumulation in the septum. Changes observed in other brain areas were not statistically significant in the combined analysis of all four experiments. This selective change in the septum is consistent with selective uptake of ORG 2766 in this region, and with the lack of behavioral activity of ACTH in septal lesioned animals. It also suggests that the behavioral activity of this peptide, generally considered to be on arousal, vigilance, and/or selective attention, may be mediated through the septum, a limbic system structure.
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PMID:Cerebral 2-deoxyglucose accumulation in mice following chronic treatment with an ACTH4-9 analog, ORG 2766. 632 82

In three experiments, 6- to 7-week-old chickens were exposed to one or two standard heating episodes and were injected immediately afterward with different concentrations of heat-killed Salmonella pullorum antigen (Ag) or phosphate-buffered saline. The standard heat episode consisted of three .5-hr exposures of 44 to 46 C with .5-hr periods of 22 C between exposures. Nonheated chickens were maintained at 22 C. When two heating episodes were used, there was a 12-hr interval between episodes. Sera from blood collected at 0 through 15 days postimmunization (PI) were titrated for total agglutinins and assayed for corticosteroids in all three experiments. Additionally, in Experiment 3, sera were titrated for 2-mercaptoethanol-resistant (2-MER) antibody. Total agglutinins were suppressed from 5 through 13 days PI by one heating episode in birds receiving lower doses of Ag but not in those receiving higher doses. When birds were exposed to two heat episodes, 12 hr apart, total agglutinin titers were suppressed in birds receiving the low Ag dose during the induction phase (4 to 5 days PI) only. During the declining phase (7 to 14 days PI), the effect was reversed, and titers were significantly lower in heated birds receiving the higher dosage. These results are similar to those previously obtained with ACTH (adrenocorticotropin). Determination of 2-MER antibody indicated that IgM was probably suppressed during the induction of the immune response but that IgG was suppressed during the declining phase of the response. Serum corticosteroid concentrations were significantly increased immediately after exposure to high temperature.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interaction of high temperature and Salmonella pullorum antigen concentration on serum agglutinin and corticosteroid responses in white rock chickens. 653 35


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