Inhibition of adrenocorticotropic hormone secretion in the rat by immunoneutralization of corticotropin-releasing factor

Intravenous administration of rabbit antiserum to ovine corticotropin-releasing factor (CRF) markedly reduced the CRF-induced rise of plasma adrenocorticotropic hormone (ACTH) in intact nonstressed adult male rats while blocking more than 75 percent of the ACTH release observed in rats exposed to ether stress. Furthermore, antiserum to CRF significantly lowered ACTH levels in adrenalectomized animals. These results suggest that endogenous CRF plays a physiological role in regulating ACTH secretion.     

促肾上腺皮质激素释放激素对离体斑马鱼卵细胞类固醇激素合成的影响

在硬骨鱼类中,促肾上腺皮质激素释放激素(CRH)在内分泌、自主神经活动、免疫、渗透压和摄食活动中起着至关重要的作用,但有关CRH是否对斑马鱼卵细胞类固醇激素合成的研究较少。以体外培养斑马鱼卵细胞为实验材料,通过荧光定量PCR技术和放射性免疫方法,检测CRHα和CRHβ处理后卵细胞中CRH受体(CRHR1和CRHR2)及类固醇激素合成相关基因的表达变化,并检测培养液中雌二醇和孕酮的含量。结果显示,100 nmol/L CRHα和CRHβ处理后,卵细胞中CRHR1基因表达量显著上调,CRHR2基因表达无显著变化。CRHβ显著增加卵细胞中cyp19a1a基因表达,CRHα和CRHβ对其他类固醇激素合成相关基因的表达无显著影响。添加CRHα和CRHβ后,培养液中雌二醇的含量显著降低,孕酮的含量无明显影响。提示CRH可能通过斑马鱼卵细胞中CRHR1调节雌激素合成相关基因的表达抑制雌激素的合成。     

A parathyroid hormone inhibitor in vivo: design and biological evaluation of a hormone analog

A synthetic analog of bovine parathyroid hormone (bPTH), [tyrosine-34] bPTH-(7-34)NH2, was found to inhibit parathyroid hormone action in vivo. When the analog and parathyroid hormone were infused simultaneously to rats at a molar ratio of 200 to 1, the analog inhibited the excretion of urinary phosphate and adenosine 3',5'-monophosphate. When infused alone at the same dose rate, the analog was devoid of agonist activity. The compound was prepared by following design principles developed for inhibitors of parathyroid hormone, and is believed to be the first antagonist of parathyroid hormone that is effective in vivo.     

Spinophilin blocks arrestin actions in vitro and in vivo at G protein-coupled receptors

Arrestin regulates almost all G protein-coupled receptor (GPCR)-mediated signaling and trafficking. We report that the multidomain protein, spinophilin, antagonizes these multiple arrestin functions. Through blocking G protein receptor kinase 2 (GRK2) association with receptor-Gbetagamma complexes, spinophilin reduces arrestin-stabilized receptor phosphorylation, receptor endocytosis, and the acceleration of mitogen-activated protein kinase (MAPK) activity following endocytosis. Spinophilin knockout mice were more sensitive than wild-type mice to sedation elicited by stimulation of alpha2 adrenergic receptors, whereas arrestin 3 knockout mice were more resistant, indicating that the signal-promoting, rather than the signal-terminating, roles of arrestin are more important for certain response pathways. The reciprocal interactions of GPCRs with spinophilin and arrestin represent a regulatory mechanism for fine-tuning complex receptor-orchestrated cell signaling and responses.     

Progesterone administration in vivo stimulates release of luteinizing hormone-releasing hormone in vitro

The release of luteinizing hormone-releasing hormone (LHRH) from tissue from the mediobasal hypothalamic-anterior hypothalamic-preoptic area of prepuberal female rats was measured in a perfusion system. Measurements were also made of the concentrations of LHRH in these tissue fragments and of luteinizing hormone in serum obtained when the rats were killed. Four groups of immature rats were studied: intact, ovariectomized, ovariectomized and implanted with estradiol-containing capsules, and ovariectomized rats primed with estradiol and injected with progesterone. The release of LHRH from the tissue of ovariectomized animals was significantly less than that of intact females and was not modified when the ovariectomized rats received estradiol. However, there was a four- to fivefold increase in LHRH release from tissue of ovariectomized rats primed with estradiol when they were killed 6 hours after they received an injection of progesterone. The concentrations of LHRH in tissue and of luteinizing hormone in serum varied among groups and with the time of day that the animals were killed. The interactions among luteinizing hormone, gonadal steroids, and the photoperiod seem to set the appropriate conditions for neural processes triggering a complete and normal release of luteinizing hormone.     

Autocrine stimulation of intracellular PDGF receptors in v-sis-transformed cells

Autocrine activation of platelet-derived growth factor (PDGF) receptors is the mechanism of transformation by the v-sis oncogene. Since the addition of PDGF does not transform normal cells, autocrine mechanisms may involve unique pathways of receptor activation. In this study autocrine stimulation of the PDGF receptor was observed in v-sis-transformed normal rat kidney (NRK) cells. In contrast to receptor activation in normal cells, autocrine activation of PDGF receptors in v-sis-transformed cells occurred in intracellular compartments, disrupting receptor processing and diverting receptors and their precursors to a chloroquine-sensitive degradation pathway. These findings show that intracellular activation of receptors by autocrine mechanisms may play a role in cell transformation.     

Similarity of synthetic peptide from human tumor to parathyroid hormone in vivo and in vitro

One mechanism considered responsible for the hypercalcemia that frequently accompanies malignancy is secretion by the tumor of a circulating factor that alters calcium metabolism. The structure of a tumor-secreted peptide was recently determined and found to be partially homologous to parathyroid hormone (PTH). The amino-terminal 1-34 region of the factor was synthesized and evaluated biologically. In vivo it produced hypercalcemia, acted on bone and kidney, and stimulated 1,25-dihydroxy-vitamin D3 formation. In vitro it interacted with PTH receptors and, in some systems, was more potent than PTH. These studies support a long-standing hypothesis regarding pathogenesis of malignancy-associated hypercalcemia.     

Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients

The possibility that hypersecretion of corticotropin-releasing factor (CRF) contributes to the hyperactivity of the hypothalamo-pituitary-adrenal axis observed in patients with major depression was investigated by measuring the concentration of this peptide in cerebrospinal fluid of normal healthy volunteers and in drug-free patients with DSM-III diagnoses of major depression, schizophrenia, or dementia. When compared to the controls and the other diagnostic groups, the patients with major depression showed significantly increased cerebrospinal fluid concentrations of CRF-like immunoreactivity; in 11 of the 23 depressed patients this immunoreactivity was greater than the highest value in the normal controls. These findings are concordant with the hypothesis that CRF hypersecretion is, at least in part, responsible for the hyperactivity of the hypothalamo-pituitary-adrenal axis characteristic of major depression.     

Inhibition of gastric acid secretion in rats by intracerebral injection of corticotropin-releasing factor

Intracisternal injection of ovine corticotropin-releasing factor (CRF) into the pylorus-ligated rat or the rat with gastric fistula resulted in a dose-dependent inhibition of gastric secretion stimulated with pentagastrin or thyrotropin-releasing hormone. When injected into the lateral hypothalamus--but not when injected into the cerebral cortex--CRF suppressed pentagastrin-stimulated acid secretion. The inhibitory effect of CRF was blocked by vagotomy and adrenalectomy but not by hypophysectomy or naloxone treatment. These results indicate that CRF acts within the brain to inhibit gastric acid secretion through vagal and adrenal mechanisms and not through hypophysiotropic effects.     

Synthetic competitive antagonists of corticotropin-releasing factor: effect on ACTH secretion in the rat

Polypeptide analogs of the known members of the corticotropin-releasing factor (CRF) family were synthesized and tested in vitro and in vivo for enhanced potency or competitive antagonism. Predictive methods and physicochemical measurements had suggested an internal secondary alpha-helical conformation spanning about 25 residues for at least three members of the CRF family. Maximization of alpha-helix-forming potential by amino acid substitutions from the native known sequences (rat/human and ovine CRF, sauvagine, and carp and sucker urotensin 1) led to the synthesis of an analog that was found to be more than twice as potent as either of the parent peptides in vitro. In contrast, certain amino-terminally shortened fragments, such as alpha-helical CRF or ovine CRF residues 8 to 41, 9 to 41, and 10 to 41, were found to be competitive inhibitors in vitro. Selected antagonists were examined and also found to be active in vivo.     

猪生长激素的研究进展

对猪生长激素的基因表达、分离纯化等方面的研究进展进行综述。猪生长激素的生产路线主要为:将猪生长激素基因转移到微生物中进行高效表达,表达产物经分离纯化获得纯品。猪生长激素产量低制约着其进一步应用。菌种构建、高密度培养及分离纯化等技术的发展有利于产量的提高。     

Intranuclear localization of mercury in vivo

Purified nuclei isolated from mice challenged with nonlethal levels of mercury chloride (10-(3)M) in drinking water for 4 to 7 weeks (experimental) and from animals given deionized water (control) were fractionated and the subsequent fractions were analyzed for mercury by flameless atomic absorption. Control (active) euchromatin contained 1.75 +/- 0.53 micrograms of mercury per milligram of DNA. There was a 12- to 15-fold enrichment of mercury in the euchromatin fraction of challenged animals. Mercury was not detected in control (inactive) heterochromatin, and only trace levels (parts per billion) appeared in experimental heterochromatin. It seems likely that mercury can be incorporated into chromatin as a metal-protein complex, but the possibility of protein-mercury-DNA or mercury-DNA complexes within euchromatin cannot be excluded.     

Opposite synaptic actions mediated by different branches of an identifiable interneuron in Aplysia

Among the identifiable cells in the abdominal ganglion of Aplysia californica are five that generate bursting rhythms endogenous to the cells. In the four bursting cells of the left upper quadrant the rhythm is modulated by a unitary inhibitory postsynaptic potential; in the bursting cell of the right lower quadrant the rhythm is modulated by a unitary excitatory postsynaptic potential. Both the excitatory and inhibitory postsynaptic potentials are mediated by separate branches of a single interneuron. The pharmacological properties of the double action interneuron as well as those of the follower cells suggest that a single transmitter (acetylcholine) is involved in both the excitatory and the in-hibitory action of the interneuron.     

嗜酸乳杆菌不同成分体外抗TGEV作用的研究

文章探讨嗜酸性乳杆菌不同成分在抗猪传染性胃肠炎病毒(TGEV)中的作用,并分析益生菌抗病毒可能存在的机制。试验分离嗜酸乳杆菌不同成分和TGEV氨肽酶受体抑制剂Bestatin,按照感染后处理组、处理后感染组和同时感染处理组试验。采用MTT法,在猪睾丸细胞(ST)上评价各成分对TGEV抑制作用。在Bestatin封闭ST细胞基础上添加S-层蛋白,研究二者联合作用。结果表明,抑制率大小顺序:S-层蛋白菌体脱S-层蛋白菌体代谢产物牛血清白蛋白。S-层蛋白对TGEV抑制作用与Bestatin相当。由此可知,嗜酸乳杆菌S-层蛋白对TGEV在ST细胞上的复制有抑制作用。氨肽酶抑制剂Bestatin预先处理ST细胞对S-层蛋白抑制TGEV的感染具有协同作用。     

三种炎症因子在致炎大鼠乳腺组织中的表达

为探明在酯多糖（LPS）致炎的大鼠乳腺中,黏附因子-1（ICAM-1）、肿瘤坏死因子-α（TNF-α）、白介素-1β（IL-1β）表达分布的变化。取产后5 d乳房注射LPS致炎大鼠的乳腺组织,及LPS致伤的体外培养大鼠乳腺MVECs（Microvascular Endothelial Cells）,采用免疫组化方法检测ICAM-1、TNF-α和IL-1β的表达。结果表明：LPS处理大鼠乳腺后4~24 h内,乳腺组织切片试验和体外培养大鼠乳腺微血管内皮细胞（Rat MammaryMicrovascular Enclothelial Cells,RMMVECs）试验中ICAM-1和IL-1β的表达逐渐增强,TNF-α在乳腺组织切片试验中6 h表达显著增强,之后则逐渐减弱。在体外培养RMMVECs中-α表达逐渐增强。表达部位主要在乳腺上皮细胞和血管内皮细胞,IL-1β在腺泡腔中的白细胞中也有表达。由此可见,LPS处理大鼠乳腺后ICAM-1、TNF-α和IL-1β这三种细胞因子均参与了乳腺炎症过程中的免疫反应。