Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Postnatal thermogenesis in sheep is associated with increased sympathoadrenal activities, a T3 surge and an enhanced brown adipose tissue (BAT) type II 5'-monodeiodinating (5'-MDI) activity. The latter peaks 3-4 days after birth and is known to be important in generating intracellular T3 for nuclear receptor binding. In order to further investigate the mechanism(s) responsible for neonatal thermogenesis, thyroid hormone nuclear receptor (T3NR) binding characteristics were quantified in lamb BAT from newborn (NB) to 30d of postnatal age. Maximal binding capacities (MBC, mean +/- SEM fmoles T3/mg DNA) in BAT showed a decrease as studied by ANOVA during the first 11 days (NB to 1d, 148 +/- 24 [N = 5, p < 0.01, cf. 3-5d group]; 3-5 d, 61 +/- 5.5 [N = 5]; 10-11d, 72 +/- 9.1 [N = 4]). Afterwards, MBC increased at 30d (196 +/- 32, N = 4, p less than 0.01, cf. 3-5d group). BAT T3NR binding affinities (10(9) M-1) were comparable in all age groups studied (NB-1d, 2.8 +/- 0.3; 3-5d, 3.4 +/- 0.3; 10-11d, 4.0 +/- 1.1; 30d, 2.4 +/- 0.4). The data suggest that the postnatal surge in T3 and type II 5'-MDI is accompanied with a concurrent decrease in MBC of BAT T3NR. The latter may represent a down-regulation of T3NR presumably in an attempt to regulate the overall effect of thyroid hormone in neonatal thermogenesis.
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PMID:Analysis of nuclear 3,3',5-triiodothyronine receptor in the brown adipose tissue (BAT) of the postnatal lamb. 142 12

The authors have measured the androgen receptor concentrations in the cytosol and nucleus of 13 carcinoma of the prostate (CaP) patients and compared these values to those in an age-matched group of 23 patients with benign prostatic hyperplasia (BPH). Histologic classification of the tumors was carried out and the receptor content was correlated to the grade and stage of the disease. The mean +/- SEM receptor values for BPH (cytosol: 115 +/- 18 fmol/g tissue; nucleus: 140 +/- 34 fmol/g tissue) were not significantly different from those measured in CaP (cytosol: 105 +/- 23 fmol/g tissue; nucleus: 83 +/- 23 fmol/g tissue). There was a positive correlation between nuclear and cytosolic receptors in both BPH and CaP. Our data revealed, however, the absence of any correlation between histologic grade in CaP and receptor content. If, however, the tumors were classified according to the stage of the cancer using the TNM system, "early disease" tumors maintained significantly lower Gleason score (4.4 +/- 0.61) and receptor levels (cytosol: 63.8 +/- 31.2 fmol/g tissue; nucleus: 46.2 +/- 26.5 fmol/g tissue) than those measured in the "late disease" (Gleason score: 7.0 +/- 0.56; cytosol receptor: 146.2 +/- 20.5; nuclear receptor: 117.2 +/- 31.6) (P less than 0.05); therefore the staging of the disease bears a great impact on the capacity of the tumor to specifically bind androgens.
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PMID:Androgen receptors in cancer of the prostate. Correlation with the stage and grade of the tumor. 242 68

1. We studied a brominated thyroid hormone analogue, SKF L-94901, which has the potential to lower serum cholesterol without adverse cardiovascular effects. This compound is about 50% as active as tri-iodothyronine (T3) in liver nuclear receptor binding in vivo but only 1% as active in vitro and has nearly 200 times more enzyme-inducing activity in liver than in heart. Our aim was to examine the interaction of SKF L-94901 with [125I]T3 binding to the intact nuclei in whole cells, isolated nuclei and nuclear extracts of human HeLa cells and to investigate the binding of this compound to human serum. 2. Relative to thyroxine (T4), the affinity of this compound for T4-binding globulin was 0.0035%, for transthyretin 1.66% and for albumin 1.26%. Low affinity for serum proteins, with a relatively high circulating free fraction, could explain why SKF L-94901 is more potent in vivo than in vitro. 3. Human HeLa cell nuclei, isolated after whole-cell incubations, bound [125I]T3 with high affinity (Kd = 78 +/- 8 pmol/l, mean +/- SEM), which was displaceable by T3 analogues in the order Triac [( 4-(4-hydroxy-3-iodophenoxy)-3,5-di-iodophenyl]acetic acid) greater than T3 greater than T4 much greater than reverse T3. Similar high-affinity (Kd = 58 +/- 6 pmol/l, mean +/- SEM) and identical specificity was observed in high-salt (0.4 mol/l KCl) nuclear extracts. In nuclei of whole cells incubated with [125I]T3 and SKF L-94901, the analogue was 0.8% as potent as T3, whereas in experiments with nuclear extract, the analogue was 7.7% as potent as T3.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The thyroid hormone analogue SKF L-94901: nuclear occupancy and serum binding studies. 272 Nov 16

The maximal binding capacity (MBC) of the rat cerebrocortical nuclear T3 receptor, as determined by in vivo saturation techniques, is approximately half that measured in vitro on isolated nuclei or solubilized receptors. To investigate this disparity, the MBC values determined in vivo and in vitro for both rat cerebral cortex and liver were compared, taking into account nuclear receptor loss or inactivation and the presence of endogenous T3. By Scatchard analysis of T3 binding to isolated nuclei in vitro at 37 C, the uncorrected MBC values (mean +/- SEM; n = 3) for the cerebrocortical nuclear T3 receptor in euthyroid and hypothyroid rats were 0.80 +/- 0.14 and 0.66 +/- 0.07 ng T3/mg DNA, respectively, and were not significantly different. The Kd values were also not significantly different (5.6 +/- 0.3 and 5.2 +/- 0.9 X 10(-10) M, respectively). After corrections for incomplete dissociation and receptor inactivation under the in vitro conditions, the overall mean MBC increased by approximately 33% to 0.97 ng T3/mg DNA, or about 3.6 times the in vivo MBC. In addition, cerebrocortical nuclei prelabeled in vivo with +/- 131I]T3 at near-saturating levels and subsequently incubated with [125I]T3 in vitro at concentrations up to 10 times the Kd were shown to bind as much as 4 times more T3 in vitro relative to the amount of endogenous hormone which dissociated, thus exceeding the in vivo MBC by a factor of two. Parallel experiments with isolated liver nuclei did not show the existence of nuclear T3 receptors which were available only in vitro, even when the corrected MBC (0.77 ng T3/mg DNA) was compared with the MBC obtained by the in vivo saturation technique (0.76 ng T3/mg DNA). The experiments with liver nuclei were done at 25 C to reduce the rate of inactivation or loss of nuclear T3 receptors in this tissue. By fractionating isolated cerebrocortical nuclei into neuronal and glial subpopulations on discontinuous sucrose gradients, the high affinity, limited capacity nuclear T3 receptor could only be identified in the neuronal fraction. No consistent specific binding of T3 was observed in glial nuclei that were 80% pure, suggesting that either glial cells in the adult rat are not likely to be direct targets of thyroid hormone or that thyroid hormone may act via nonnuclear receptor-mediated pathways. We conclude that only neurons have specific high affinity, limited capacity nuclear T3 receptors and that as many as half of these receptors may not be accessible to plasma T3.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:In vitro 3,5,3'-triiodothyronine binding to rat cerebrocortical neuronal and glial nuclei suggests the presence of binding sites unavailable in vivo. 298 67

Physiochemical properties of an estrogen binding protein were characterized in three human melanoma cell lines, UISO-MEL-1, UISO-MEL-2, and UISO-MEL-4. Estrogen binding to melanoma cytosol was saturable, specific for estrogens, and represented by a single class of high-affinity, limited-capacity binding sites (Kd 5.5 x 10(-10) M, 2.7 +/- 0.5 fmol/mg of cytosol protein, UISO-MEL-2; 2.2 x 10(-10) M, 7.8 +/- 3.3, UISO-MEL-4) (SEM). UISO-MEL-1 cytosols did not bind estradiol. The binding protein in UISO-MEL-2 and -4 sedimented at 8.5S and 9.2S, respectively, in the presence of 10 mM sodium molybdate. Solid-phase radioimmunoassay with a monoclonal antibody specific for human estrogen receptor (H222 sp lambda) showed good correlation (r = 0.84) with a hydroxyapatite biochemical assay of identical melanoma cytosols. Exposure of UISO-MEL-2 to estradiol produced a time- and temperature-dependent increase in total nuclear receptor for estrogen in vitro. Estradiol treatment of athymic mice also significantly increased cytosol progesterone receptor content in UISO-MEL-2 and UISO-MEL-4 xenografts. Estradiol had no effect on the plating efficiency or growth of any melanoma cell line or normal melanocytes in vitro. Tamoxifen also had no effect on melanoma growth in vitro. In contrast, chronic exposure of athymic mice carrying estrogen receptor-positive UISO-MEL-2 to estradiol resulted in a sex-dependent increase in tumor latency and overall inhibition of tumor growth. Taken together, these observations suggest that a subset of human melanomas contains limited amounts of an estrogen binding protein similar to that observed in other estrogen-responsive tissues. The lack of effect of estradiol on melanocyte and melanoma growth in vitro, coupled with a decrease in tumor growth in athymic mice, suggests that, while inhibition may be receptor mediated, possible indirect actions of estradiol must also be considered.
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PMID:Effect of 17 beta-estradiol on the growth of estrogen receptor-positive human melanoma in vitro and in athymic mice. 319 86

Retinol deficiency in animal models results in histopathologic airway changes that appear similar to those found in human premature infants with bronchopulmonary dysplasia (BPD). Dexamethasone (DEX), a steroid now often used in the treatment of BPD, might potentially affect lung vitamin A homeostasis since it alters serum and liver retinoid stores in certain models. Our objective was to determine the effect of DEX on neonatal rat lung retinoid status and the binding of retinoic acid (RA) to cytosolic and nuclear receptor proteins. We examined this effect both in room air and when the animals breathed 95% oxygen (O2). Twenty-four 1-day-old rat pups received either 1 microgram/g DEX subcutaneously, an equal volume of normal saline (NS) subcutaneously at 0 (start experiment time), 24, and 48 hours, or no injection at all, and were sacrificed at 72 hours. Twelve rats in each treatment group were housed in room air and 12 in each group were exposed to > 95% O2 for the 3 day period. Lung and liver were analyzed for retinyl palmitate (RP). Nuclear retinoic acid receptor (RAR) and cellular retinoic acid binding protein (CRABP) were measured by specific binding assays. DEX decreased liver RP by 33-55% and rat pup lung RP by over 60%; it also decreased lung RAR binding (mean dpm/microgram protein +/- SEM) in both room air and oxygen groups: Air (11.2 +/- 1.0) vs. Air/DEX (4.6 +/- 1.3, n = 6; P < 0.01), and O2 (18.2 +/- 0.6) vs. O2/DEX (3.2 +/- 0.6, n = 6; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of dexamethasone and oxygen exposure on neonatal rat lung retinoic acid receptor proteins. 783 22

Clinical studies have suggested that hormone replacement therapy (HRT) may reduce the risk of coronary heart disease in postmenopausal women. Although progestins are commonly added to HRT preparations for uteroprotection, the perceived beneficial cardiovascular effects of HRT are thought to be mediated predominantly by the estrogen component. Platelets play a critical role in the pathogenesis of atherosclerosis and cardiovascular disease and, hence, it is possible that the cardiovascular effects of estrogens are mediated, at least in part, through inhibition of illicit platelet activation. The aim of this study was to examine the effects of sex steroids on adenosine diphosphate (ADP)-induced platelet aggregation and adenosine triphosphate (ATP) release in vitro in postmenopausal women. In addition, the effects of antiestrogens 14-hydroxy tamoxifen (4-OHT) and ICI 182780] and antiprogestins (RU 486 and ZK 98299) were also investigated. Preincubation of platelet-rich plasma (PRP) with antiestrogens or antiprogestins did not alter subsequent platelet aggregation or ATP release in response to ADP. However, preincubation with 17beta-estradiol (E2) significantly inhibited ADP-mediated platelet aggregation by a mean (+/-SEM) of 37%+/-6% (p = 0.02) and ATP release by 82%+/-6% (p = 0.03), an effect that was reversed by the addition of ICI 182780 or 4-OHT but not RU 486 and ZK 98299. Although the progestin medroxyprogesterone acetate (MPA) also significantly inhibited platelet aggregation (by 28%+/-5%, p = 0.02) and ATP release (by 63%+/-9%, p = 0.02), this inhibition was not reversed by the addition of antiprogestins or antiestrogens. These data show that sex steroids can modulate platelet function in vitro. Furthermore, as platelets are devoid of nuclear components, these findings indicate that estrogens may regulate platelet function through binding to a non-nuclear receptor with ligand-binding properties similar or identical to the wild-type receptor. By contrast, MPA appears to exert its effect through a mechanism that does not involve binding to the "classical" progesterone receptor.
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PMID:Regulation of platelet aggregation and adenosine triphosphate release in vitro by 17beta-estradiol and medroxyprogesterone acetate in postmenopausal women. 1105 72