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1.
Summary For the study of the hypothalamo-hypophysial system of Xenopus laevis tadpoles, hypothalamic lesions were made by means of the electrocoagulation technique. Lesioning of the ventral region of the preoptic nucleus resulted in a decrease of the number of ACTH cells in the pars distalis of the pituitary gland and in a diminution of the PAS-positive reaction of these cells. In addition, regeneration of the neurosecretory cells of the ventral region of the preoptic nucleus observed 6 weeks after lesioning was accompanied by the reappearance of normal PAS-positive ACTH cells in the pars distalis. It is suggested that the neurosecretory cells of the ventral region of the preoptic nucleus of Xenopus laevis tadpoles are related to the ACTH synthesizing cells, probably by producing CRF.Dedicated to Prof. Dr. med. W. Bargmann on the occasion of his 70th birthdayThe authors thank Prof. Dr. J.C. van de Kamer for his interest, Prof. Dr. P.G.W.J. van Oordt for his many helpful comments, and Messrs. H. van Kooten, E. van der Vlist, J.J. van der Vlis and M.C.A. van Pinxteren for preparing the illustrations 相似文献
2.
Summary The interrelationships of corticotropin-releasing factor (CRF) immunoreactive neuronal cell bodies and processes have been examined in the paraventricular nucleus (PVN) of adrenalectomized-dexamethesone treated rats. Antisera generated against ovine CRF (oCRF) were used in the peroxidase-anti-peroxidase-complex (PAP)-immunocytochemical method at both the light and electron microscopic levels. In this experimental model, a great number of CRF-immunoreactive neurons were detected in the parvocellular subdivisions of the PVN and a few scattered labelled parvocellular neurons were also observed within the magnocellular subunits. Characteristic features of immunolabeled perikarya included hypertrophied rough endoplasmic reticulum with dilated endoplasmic cisternae, well developed Golgi complexes and increased numbers of neurosecretory granules. These features are interpreted to indicate accelerated hormone synthesis as a result of adrenalectomy. Afferent fibers communicated with dendrites and somata of CRF-immunoreactive neurons via both symmetrical and asymmetrical synapses. Some neurons exhibited somatic appendages and these structures were also observed to receive synaptic terminals. Within both the PVN and its adjacent neuropil, CRF-immunoreactive axons demonstrated varicosites which contained accumulations of densecore vesicles. CRF-containing axons were observed to branch into axon collaterals. These axons or axon collaterals established axo-somatic synapses on CRF-producing neurons in the parvocellular regions of the PVN, while in the magnocellular area of the nucleus they were found in juxtaposition with unlabeled magnocellular neuronal cell bodies or in synaptic contact with their dendrites. The presence of CRF-immunoreactive material in presynaptic structures suggests that the neurohormone may participate in mechanisms of synaptic transfer.These ultrastructural data indicate that the function of the paraventricular CRF-synthesizing neurons is adrenal steroid hormone dependent. They also provide morphological evidence for the existence of a neuronal ultrashort feedback mechanism within the PVN for the regulation of CRF production and possibly that of other peptide hormones contained within this complex.Supported by NIH grant NS 19266 to WKP 相似文献
3.
J W Kendall D K Gray N D Gaudette 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1976,152(4):691-694
The ACTH-releasing activity of hypothalamic extract and rat plasma was examined with the dispersed rat pituitary cell technique of Swallow and Sayer (8). Although both plasma and serum caused ACTH release which was dose-related, stress did not enhance the ACTH releasing activity. Furthermore, separation studies of plasma using ultrafiltration and gel separation suggest that the CRF activity in plasma is associated with molecules of a molecular weight greater than 15,000. 相似文献
4.
The interrelationships of corticotropin-releasing factor (CRF) immunoreactive neuronal cell bodies and processes have been examined in the paraventricular nucleus (PVN) of adrenalectomized-dexamethasone treated rats. Antisera generated against ovine CRF (oCRF) were used in the peroxidase-anti-peroxidase-complex (PAP)-immunocytochemical method at both the light and electron microscopic levels. In this experimental model, a great number of CRF-immunoreactive neurons were detected in the parvocellular subdivisions of the PVN and a few scattered labelled parvocellular neurons were also observed within the magnocellular subunits. Characteristic features of immunolabeled perikarya included hypertrophied rough endoplasmic reticulum with dilated endoplasmic cisternae, well developed Golgi complexes and increased numbers of neurosecretory granules. These features are interpreted to indicate accelerated hormone synthesis as a result of adrenalectomy. Afferent fibers communicated with dendrites and somata of CRF-immunoreactive neurons via both symmetrical and asymmetrical synapses. Some neurons exhibited somatic appendages and these structures were also observed to receive synaptic terminals. Within both the PVN and its adjacent neuropil, CRF-immunoreactive axons demonstrated varicosites which contained accumulations of densecore vesicles. CRF-containing axons were observed to branch into axon collaterals. These axons or axon collaterals established axo-somatic synapses on CRF-producing neurons in the parvocellular regions of the PVN, while in the magnocellular area of the nucleus they were found in juxtaposition with unlabeled magnocellular neuronal cell bodies or in synaptic contact with their dendrites. The presence of CRF-immunoreactive material in presynaptic structures suggests that the neurohormone may participate in mechanisms of synaptic transfer. These ultrastructural data indicate that the function of the paraventricular CRF-synthesizing neurons is adrenal steroid hormone dependent. They also provide morphological evidence for the existence of a neuronal ultrashort feed-back mechanism within the PVN for the regulation of CRF production and possibly that of other peptide hormones contained within this complex. 相似文献
5.
Summary Corticotropin releasing factor (CRF), synthesized in neurons of the hypothalamic paraventricular nucleus (PVN), is one of the main regulators of the pituitaryadrenal cortex endocrine axis. In order to elucidate the possible involvement of the central neuropeptide-Y (NPY)-and adrenocorticotroph hormone (ACTH)-immunoreactive (IR) systems in the innervation of hypophysiotrophic CRF-synthesizing neurons, immunocytochemical double labelling studies were conducted in the hypothalamus of the rat to localize CRF-synthesizing neurons, as well as neuronal fibers exhibiting NPY and ACTH-immunoreactivity, respectively.The parvocellular subnuclei of the PVN received an intense NPY-and ACTH-IR innervation. At the light microscopic level, these peptidergic axons were associated with the dendrites and perikarya of CRF-IR neurons. Ultrastructural analysis revealed that NPY- and ACTH-IR axons established synaptic specializations with parvocellular neurons expressing CRF-immunoreactivity. These findings indicate that both neuropeptide-Y and adrenocorticotroph hormone containing neuronal systems of the brain are capable of influencing adrenal function via synaptic interactions with hypophysiotrophic CRF-synthesizing neurons. The data also support the concept that NPY and ACTH might be ntilized as neuromodulators within the PVN.Dedicated to Professor Dr. T.H. Schiebler on the occasion of his 65th birthday 相似文献
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7.
S J Konturek C Yanaihara N Yanaihara T Mochizuki J Bilski A Dembinski J Jaworek 《Peptides》1987,8(3):575-577
Human CRF given IV inhibited dose-dependently pentagastrin- but not histamine-induced gastric acid secretion. When added to the incubation medium of the isolated gastric glands, CRF did not alter the formation of HCl under basal conditions or after stimulation with histamine or DBcAMP. CRF caused a small but significant increase in pancreatic HCO3 and protein secretion. It augmented CCK-induced pancreatic protein and secretin-induced HCO3 secretion in vivo but failed to affect basal or stimulated (CCK and urecholine) amylase release by the in vitro dispersed pancreatic acini. This study indicates that CRF inhibits gastric and stimulates pancreatic secretion in vivo but not in vitro and these effects are indirect involving, at least in part, alterations in the pancreatic circulation. 相似文献
8.
The distribution of corticotropin releasing factor (CRF)-like immunoreactivity in the rat brain has been demonstrated by immunohistochemistry and radioimmunoassay using 4 different antisera. Two antisera were directed against synthetic ovine CRF, two antisera were directed against synthetic rat/human CRF. Immunohistochemistry revealed that there are discrete regions where CRF immunoreactive cell bodies are seen with all 4 antisera (e.g., the paraventricular nucleus, the dorsolateral tegmental nucleus) whereas there are cells observed only with one rat CRF antiserum (e.g., in the cortex) or terminal fields observed only with ovine CRF antisera (e.g., the spinal trigeminal tract, the substantia gelatinosa, the spinal cord). Radioimmunoassay showed different cross reactivity of the antisera with synthetic ovine or rat/human CRF and sauvagine, however, there was no cross reactivity with a variety of other peptides. Tissue values of CRF obtained by RIA of micropunched brain nuclei with the 4 antisera were frequently dissimilar suggesting that different antisera recognize different substances. High performance liquid chromatography and radioimmunoassay of brain tissue samples, revealed that there is more than one form of CRF-like immunoreactivity present. There is indirect evidence that there exists at least one peptide in the rat brain, prominent in the medulla and the spinal cord, which cross reacts with antisera directed to ovine CRF only. 相似文献
9.
ACTH release under the effect of median eminence extract (ME) was studied in both incubation and superfusion experiments. ACTH content of the incubation medium was measured by radioimmunoassay or by the corticosterone production of trypsinisolated adrenocortical cells. Dopamine at low concentration led to a slight increase of basal ACTH secretion, while at higher concentration failed to influence ACTH release. The dopamine agonist CB-154 produced a significant rise of ACTH secretion and augmented the ME extract-induced increase of pituitary ACTH release. Chlorpromazine and haloperidol suppressed basal ACTH secretion and inhibited the ME extract-induced release. The simultaneous administration of CB-154 and haloperidol into the incubation medium prevented the haloperidol-induced inhibition of ACTH release. The observations indicate that dopaminergic receptors play a role in the activation of CRF-induced ACTH secretion under in vitro experimental conditions. 相似文献
10.
Goat hypothalamic extract prepared by HCl extraction and chromatographed on a Sephadex G-50 column showed two immunoreactive CRF peaks. Most of the immunoreactivity coeluted with synthetic ovine CRF, and a small peak eluted near the void volume. Bovine, monkey, rat and human hypothalamic extracts prepared by acid-acetone or acid-methanol extraction showed three immunoreactive peaks. Most of the immunoreactivity coeluted with ovine CRF, and other smaller peaks eluted near the void volume and slightly before arginine vasopressin. Goat hypothalamic extract showed the highest cross-reactivity with anti-ovine CRF serum, followed by bovine hypothalamic extract. Less cross-reactivity was found in human, rat and monkey hypothalamic extracts. CRF immunoreactivity in goat hypothalamic extract coeluted with ovine CRF on reversed phase high performance liquid chromatography (HPLC) and main CRF immunoreactivity in human and rat hypothalamic extracts eluted slightly later than ovine CRF. These results suggest that there is a heterogeneity among the CRF molecules in these species and that goat CRF may be more similar to that of sheep CRF and the amino acid sequence or molecular weight of other animals CRF may be different from that of sheep CRF. The monkey posterior pituitary and rat neurointermediate lobe showed similar elution patterns of CRF immunoreactivity to their hypothalamic extracts on Sephadex gel filtration and HPLC. These results indicate that the posterior pituitary contains a similar CRF to hypothalamic CRF. 相似文献
11.
Liposits Zsolt Görcs Tamás Sétáló György Lengvári István Flerkó Béla Vigh Sándor Schally Andrew V. 《Cell and tissue research》1983,229(1):191-196
Summary The corticotropin releasing factor (CRF)-synthesizing perikarya and neural processes were detected at ultrastructural level in the hypothalamic paraventricular nucleus and in the median eminence of control and colchicine-pretreated rats. The unlabelled antibody peroxidase-antiperoxidase complex (PAP) immunohistochemical method was used in a pre-embedding manner, on thick, non-frozen sections. In CRF-perikarya, neurosecretory granules (80–120 nm in diameter), free ribosomes, and the rough endoplasmic reticulum were labelled. Unlabelled axon terminals formed asymmetric synapses on CRF-containing perikarya and dendrites. Immunolabelled axons terminated in the palisadic zone of the median eminence. 相似文献
12.
Corticotropin releasing factor (CRF), synthesized in neurons of the hypothalamic paraventricular nucleus (PVN), is one of the main regulators of the pituitary-adrenal cortex endocrine axis. In order to elucidate the possible involvement of the central neuropeptide-Y (NPY)- and adrenocorticotroph hormone (ACTH)-immunoreactive (IR) systems in the innervation of hypophysiotrophic CRF-synthesizing neurons, immunocytochemical double labelling studies were conducted in the hypothalamus of the rat to localize CRF-synthesizing neurons, as well as neuronal fibers exhibiting NPY and ACTH-immunoreactivity, respectively. The parvocellular subnuclei of the PVN received an intense NPY- and ACTH-IR innervation. At the light microscopic level, these peptidergic axons were associated with the dendrites and perikarya of CRF-IR neurons. Ultrastructural analysis revealed that NPY- and ACTH-IR axons established synaptic specializations with parvocellular neurons expressing CRF-immunoreactivity. These findings indicate that both neuropeptide-Y and adrenocorticotroph hormone containing neuronal systems of the brain are capable of influencing adrenal function via synaptic interactions with hypophysiotrophic CRF-synthesizing neurons. The data also support the concept that NPY and ACTH might be utilized as neuromodulators within the PVN. 相似文献
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14.
The actions of the corticotropin-releasing factor (CRF) family of peptides are mediated by the seven transmembrane-domain G-protein-coupled receptors, the CRF receptors type 1 (CRF1 receptor) and type 2 (CRF2 receptor). In a previous study, we reported that CRF, an endogenous ligand for CRF1 receptor, modulated Ca2+ influx in rat pancreatic beta-cells. In addition to CRF, other additional members of the family, urocortins, have been identified in mammals. Urocortin 1 (UCN 1), a peptide of the CRF family, binds both CRF1 receptor and CRF2 receptor with equal affinities. Urocortin 3 (UCN 3), a highly selective ligand for CRF2 receptor with little affinity for CRF1 receptor, has been shown in rat pancreatic beta-cells. The present study focused on the effects of the CRF family peptides on intracellular Ca2+ ([Ca2+]i) concentration via CRF receptors in rat pancreatic beta-cells. Microfluorimetric experiments showed that CRF (0.2 nM) and UCN 1 (0.2 nM) elevated [Ca2+]i levels. Both CRF and UCN 1 effects were attenuated by astressin, a non-selective CRF receptor antagonist. Antisauvagine-30, a selective CRF2 receptor antagonist, appeared to enhance the UCN 1 effect on the elevation of [Ca2+]i. The CRF effect on the elevation of [Ca2+]i was inhibited by the addition of UCN 3. Taken together, the activation of CRF2 receptor antagonizes the CRF1 receptor-stimulated Ca2+ influx. 相似文献
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In order to investigate the possible involvement of corticotropin-releasing factor (CRF) and somatostatin (SRIF) on thyrotropin-releasing hormone (TRH) neuronal cell activity in the rat hypothalamic paraventricular nucleus, we have proceeded to the simultaneous localization of CRF or SRIF and TRH. For this purpose, we used a dual immunostaining procedure that employed antibodies to CRF and SRIF and peroxidase-labeled goat anti-rabbit IgG as a first sequence, and antibodies to a cryptic fragment (Phe178-Glu199) of pro-TRH (to label TRH neurons) and alkaline phosphatase-labeled goat anti-rabbit IgG as the second sequence. A rich innervation of the paraventricular nucleus by immunoreactive CRF and SRIF fibers was observed. A large number of CRF and SRIF nerve endings were seen intimate anatomic proximity and often appeared to surround TRH-containing cell bodies. These results strongly suggest that TRH neurons might be regulated by both CRF and SRIF. These interactions might be the neuroanatomical basis for the already observed inhibitory effects of CRF and SRIF on TRH release. 相似文献
17.
最近的大量研究表明,促肾上腺皮质激素释放激素(CRF)和CRF类似肽广泛分布于脑、脊髓和内脏器官。CRF和CRF类似肽均可与CRF受体结合。CRF受体(CRFR)可分为CRFR1、CRFR2和CRFR3三种类型。CRFR2又分为A、B、C三个亚型。各种CRF受体激活时,对细胞产生相应的功能调节。CRF参与机体多层次的痛觉调节,CRF、CRF类似肽及与CRF有关的生物活性物质都有可能成为新一代的镇痛药。 相似文献
18.
GnRH in physiological concentrations is highly degradable by both soluble and particulate fractions of rat ovarian homogenate in vitro. The two proteolytic enzyme activities differ strongly by the soluble activity showing a dithiothreitol optimum, high inhibition by diisopropyl fluorophospate (ki=0.7 μM), and a relatively high affinity (Km=1.1 μM) as opposed to the particulate fraction (Ki=3.5 mM and Km=150 μM, respectively). The results of this study show that the rat ovary is differently endowed with GnRH-degrading activity at different sites. The involvement of these in terminating the biological activity of the hormone on the ovary may possibly depend on its exact pathway in this GnRH-target organ. 相似文献
19.
Summary The morphological interrelationship between the central serotonergic and hypothalamic corticotropin-releasing factor (CRF) synthesizing systems was studied in the hypothalamic paraventricular nucleus (PVN) of colchicine pretreated male rats. The simultaneous immunocytochemical localization of the transmitter and peptide employed the peroxidase-antiperoxidase complex (PAP) technique using the silver-gold intensified (SGI) and non-intensified forms of the oxidized 3,3-diaminobenzidine (DAB) chromogen.The paraventricular nucleus received a moderate serotonergic innervation as compared with other diencephalic structures. The distribution and arborization of serotonergic axons were more prominent in the parvocellular subnuclei than in the magnocellular units of the nucleus. Serotonin containing axons formed terminal bouton and en passant type synapses with dendrites and somata of parvocellular neurons. The immunocytochemical double labelling technique revealed the overlapping of serotonergic axons and CRF-immunoreactive neurons. Vibratome (40 m) and semithin (1 m) sections indicated that the interneuronal communication may take place on both dendrites and cell bodies of CRF-immunoreactive neurons. Ultrastructural analysis demonstrated that serotonin-containing terminals formed axo-dendritic and axo-somatic synapses with CRF-immunoreactive neurons. These findings indicate that the central serotonergic neuronal system can influence the function of the pituitary-adrenal endocrine axis via a direct action upon the hypophysiotrophic CRF synthesizing neurons.Supported by NIH Grant NS19266 相似文献
20.
Acute effects of Ace, Meth and IL-1 on AChE activity, ACh and CRF mRNA levels in, and CRF-release from the hypothalamus were studied in vitro. The hypothalamus samples were dissected from the rat brain and were incubated in vitro with IL-1, Ace or Meth in the presence or absence of Dex, Atrop, PTL, PROP and GABA. Ace and Meth, but not IL-1, inhibited AChE activity, while all three compounds; (1) increased ACh and CRF mRNA levels in and CRF release from; (2) activated the CRE promoter region of CRF-gene in: and (3) increased cFos binding to the AP-1 region of the CRF-gene in the hypothalamus. Dex suppressed the effects of IL-1, possibly by inducing the nGRE regulatory sites of the CRF-gene. Dex, however, did not modulate the effects of Ace and Meth on the hypothalamus, which may be attributed to the failure of Dex to modulate the CRF-gene's nGRE regulatory sites. Atrop caused 80-90% inhibition of the effects of IL-1, but caused only 50-65% inhibition of the effects of Ace or Meth on CRF mRNA levels in and CRF release from the hypothalamus. PTL did not affect, while PROP slightly attenuated the effects of IL-1 and the insecticides on the hypothalamus. GABA attenuated the effects of the insecticides but not the effects of IL-1 on the hypothalamus. This suggests that the IL-1-induced augmentation of CRF synthesis in and release from the hypothalamus is mediated through a cholinergic pathway, while the insecticide-induced augmentation of CRF synthesis in and release from the hypothalamus is mediated through the cholinergic and GABAergic pathways. The insecticides, but not IL-1, disrupt feedback regulation of CRF synthesis in and release from the hypothalamus. 相似文献