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1.
Female steroid hormones and target cell nuclei   总被引:58,自引:0,他引:58  
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2.
A selective imidazobenzodiazepine antagonist of ethanol in the rat   总被引:9,自引:0,他引:9  
Ethanol, at pharmacologically relevant concentrations of 20 to 100 mM, stimulates gamma-aminobutyric (GABA) receptor-mediated uptake of 36Cl-labeled chlorine into isolated brain vesicles. One drug that acts at GABA-benzodiazepine receptors, the imidazobenzodiazepine Ro15-4513, has been found to be a potent antagonist of ethanol-stimulated 36Cl- uptake into brain vesicles, but it fails to antagonize either pentobarbital- or muscimol-stimulated 36Cl- uptake. Pretreatment of rats with Ro15-4513 blocks the anticonflict activity of low doses of ethanol (but not pentobarbital) as well as the behavioral intoxication observed with higher doses of ethanol. The effects of Ro15-4513 in antagonizing ethanol-stimulated 36Cl- uptake and behavior are completely blocked by benzodiazepine receptor antagonists. However, other benzodiazepine receptor inverse agonists fail to antagonize the actions of ethanol in vitro or in vivo, suggesting a novel interaction of Ro15-4513 with the GABA receptor-coupled chloride ion channel complex. The identification of a selective benzodiazepine antagonist of ethanol-stimulated 36Cl- uptake in vitro that blocks the anxiolytic and intoxicating actions of ethanol suggests that many of the neuropharmacologic actions of ethanol may be mediated via central GABA receptors.  相似文献   

3.
Mouse lymphoma cells in culture which are killed by adrenal steroids contain specific cortisol receptors that may be involved in the initial events of hormone action. The similarity of these receptors to those in hepatoma tissue culture cells, where adrenal steroids induce tyrosine aminotransferase, suggests that certain aspects of steroid action are similar in the two systems. In three steroid-resistant lymphoma cell populations specific binding was less than in the parent lines, suggesting that conversion to steroid resistance may be associated with changes in specific steroid binding.  相似文献   

4.
In addition to the electronic factors, there is a steric factor responsible for the carcinogenicity of polynuclear aromatic hydrocarbons. A carcinogenic polynuclear aromatic hydrocarbon must bear steric resemblance to steroids. One possible implication to this requirement for carcinogenicity is that these hydrocarbons may act on the same sites as steroid hormones.  相似文献   

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6.
Two representative anabolicsteroids caused an increase in the uptake of alpha-aminoisobutyric acid-1-C(14) in the levator ani muscle of rats. The distribution ratio between that muscle and the plasma was increased fourfold by the administration of a synthetic anabolic steroid and twofold by administration of testosterone propionate. The determination of this increase may serve as an indicator for the myotrophic effect of anabolic steroids.  相似文献   

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8.
The zinc content of HeLa S(3) cells is markedly increased after growth in medium containing adrenal glucocorticoid hormones. Studies with inhibitors indicate that the synthesis of RNA and protein is required for enhanced zinc uptake. When protein synthesis is blocked in the presence of the steroid, an intermediate, presumably messenger RNA, which specifies enhanced zinc uptake accumulates and is expressed when the inhibition of protein synthesis is removed.  相似文献   

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类固醇激素作为一类典型的环境内分泌干扰物,具有很强的内分泌干扰作用,对生态和环境危害极大,其主要来源于包括人类在内的脊椎动物的排放,目前已在环境中被不断检出。通过综述进入环境后类固醇激素发生的吸附、降解、迁移等环境行为的特征,从类固醇激素自身的性质和环境暴露量浓度、环境中的有机质、矿物质以及环境介质的理化性质、共存的有机污染物和微生物等方面对其影响因素进行了归纳和总结。  相似文献   

12.
Hormone-calcium interactions with the plasma membrane of rat liver cells   总被引:4,自引:0,他引:4  
The binding constants and the number of binding sites for insulin, glucagon, epinephrine, cyclic adenosine monophosphate, and calcium ions for the plasma membrane of rat liver were determined by Scatchard plots. The plots are biphasic or multiphasic, an indication of at least two types of binding sites for each ligand. At least three types of binding sites were found for insulin. In the concentration range of 10(-6) to 10(-8) molar, glucagon, epinephrine, and hydro-cortisone increased calcium ion binding to the plasma membrane, whereas insulin decreased this binding. At hormone concentrations of 10(-6) to 10(-7) molar, glucagon was the most effective in increasing calcium binding, but at a hormone concentration of 10(-8) molar, hydrocortisone was the most effective in stimulating calcium binding. Adenosine triphosphate reversed the effect of insulin and inhibited the effect of the other hormones. These studies suggest a relation between hormones and calcium with respect to membrane structure and function.  相似文献   

13.
gamma-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in mammalian brain, is believed to act by increasing membrane conductance of chloride ions. In this study it was found that GABA agonists increased the uptake of chloride-36 by cell-free membrane preparations from mouse brain. This influx was rapid (less than 5 seconds), and 13 micromolar GABA produced a half-maximal effect. The GABA antagonists (bicuculline and picrotoxin) blocked the effect of GABA, whereas pentobarbital enhanced the action. This may be the first demonstration of functional coupling among GABA and barbiturate receptors and chloride channels in isolated membranes. The technique should facilitate biochemical and pharmacological studies of GABA receptor-effector coupling.  相似文献   

14.
The heart is a target organ for androgen   总被引:5,自引:0,他引:5  
Autoradiographic and biochemical analyses of the hearts of female rhesus monkeys and baboons indicate that atrial and ventricular myocardial cells contain androgen receptors. Although the specific effects of nuclear uptake and retention of androgen on the function of heart muscle cells are not known, the presence of this receptor suggests that sex steroid hormones may affect myocardial function directly and may explain some of the peculiar differences in heart disease between men and women.  相似文献   

15.
The results of the Women's Health Initiative, a study anticipated to provide definitive answers about health benefits and risks of postmenopausal hormone therapy, have generated debate and confusion among clinicians, researchers, and the lay public. The ovarian hormones estrogen and progesterone, which decline at menopause, normally elicit complex tissue-specific responses throughout the body. Major advances are providing a detailed molecular definition of how that differential action is achieved. Here we review estrogen and progestin actions, discuss how effectively knowledge of steroid hormone endocrinology has been incorporated into clinical studies, and consider the impact on modern hormone therapy protocols and pharmaceutical development.  相似文献   

16.
Hydrogen storage in microporous metal-organic frameworks   总被引:2,自引:0,他引:2  
Metal-organic framework-5 (MOF-5) of composition Zn4O(BDC)3 (BDC = 1,4-benzenedicarboxylate) with a cubic three-dimensional extended porous structure adsorbed hydrogen up to 4.5 weight percent (17.2 hydrogen molecules per formula unit) at 78 kelvin and 1.0 weight percent at room temperature and pressure of 20 bar. Inelastic neutron scattering spectroscopy of the rotational transitions of the adsorbed hydrogen molecules indicates the presence of two well-defined binding sites (termed I and II), which we associate with hydrogen binding to zinc and the BDC linker, respectively. Preliminary studies on topologically similar isoreticular metal-organic framework-6 and -8 (IRMOF-6 and -8) having cyclobutylbenzene and naphthalene linkers, respectively, gave approximately double and quadruple (2.0 weight percent) the uptake found for MOF-5 at room temperature and 10 bar.  相似文献   

17.
The active hormonal form of vitamin D3, 1,25-dihydroxyvitamin D3[1,25(OH), which regulates cellular replication and function in many tissues and has a role in bone and calcium homeostasis, acts through a hormone receptor homologous with other steroid and thyroid hormone receptors. A 1,25(OH)2D3-responsive element (VDRE), which is within the promoter for osteocalcin [a bone protein induced by 1,25(OH)2D3] is unresponsive to other steroid hormones, can function in a heterologous promoter, and contains a doubly palindromic DNA sequence (TTGGTGACTCACCGGGTGAAC; -513 to -493 bp), with nucleotide sequence homology to other hormone responsive elements. The potent glucocorticoid repression of 1,25(OH)2D3 induction and of basal activity of this promoter acts through a region between -196 and +34 bp, distinct from the VDRE.  相似文献   

18.
Gonadotropin-releasing hormone binding sites in human breast carcinoma   总被引:6,自引:0,他引:6  
Gonadotropin-releasing hormone analogs can cause regression of hormone-dependent breast carcinomas. These effects are thought to be mediated through the inhibition of gonadotropic and steroid hormones. These analogs may also act directly on the tumor because they are effective in treating breast cancer in some postmenopausal women. The presence of specific binding sites for gonadotropin-releasing hormone was demonstrated in human breast carcinomas by means of a novel approach of ligand immunoblotting. The results indicate a possible mechanism by which the peptide has direct effects on this tissue. These binding proteins were not detectable in non-neoplastic breast tissue.  相似文献   

19.
In cultures of mouse adrenocortical tumor cells (Sato's minimal deviation Y-1 clonal strain), the acceleration of steroid biosynthesis after exposure to adrenocorticotropic hormone or cyclic adenosine 3',5'-monophosphate is maximum within 15 to 60 minutes and precedes any significant increase in labeling of protein with [4,5-(3)H]leucine. However, when cytosol proteins are separated by acrylamidegel electrophoresis, rapid changes in the amount and labeling of several protein fractions are evident in less than 30 minutes and are no longer evident within 60 minutes. This finding supports the proposal that the effects of tropic hormones and their intracellular mediators involve rapid selective effects on protein synthesis.  相似文献   

20.
Exposure to bacterial endotoxins has long been known to stimulate the release of anterior pituitary hormones; administration of endotoxin was at one time a common clinical test of anterior pituitary function. Endotoxin is a potent stimulus for production of the endogenous pyrogenic protein, interleukin-1 (IL-1), by macrophages and monocytes. The possibility that IL-1 has a direct effect on the secretion of hormones by rat pituitary cells in a monolayer culture was investigated. Recombinant human IL-1 beta stimulated the secretion of adrenocorticotropic hormone, luteinizing hormone, growth hormone, and thyroid-stimulating hormone. Increased hormone secretion into culture supernatants was found with IL-1 concentrations ranging from 10(-9) M to 10(-12) M. Prolactin secretion by the monolayers was inhibited by similar doses. These concentrations of IL-1 are within the range reported for IL-1 in serum, suggesting that IL-1 generated peripherally by mononuclear immune cells may act directly on anterior pituitary cells to modulate hormone secretion in vivo. Incubation of IL-1 solutions with antibody to IL-1 neutralized these actions. These pituitary effects of IL-1 suggest that this monokine may be an important regulator of the metabolic adaptations to infectious stressors.  相似文献   

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