bluuebunny/crossref_metadata_2025_split huggingface dataset:
Central Orexin‐A Activates Hypothalamic‐Pituitary‐Adrenal Axis and Stimulates Hypothalamic Corticotropin Releasing Factor and Arginine Vasopressin Neurones in Conscious Rats
Authors: Al‐Barazanji K. A. , Wilson S. , Baker J. , Jessop D. S. , Harbuz M. S. 
Published: March 2003

AbstractThe effects of centrally injected orexin‐A on plasma adrenocorticotropin (ACTH) and corticosterone levels and corticotropin releasing factor (CRF) and arginine vasopressin (AVP) mRNA in the parvocellular cells of the paraventricular nucleus (PVN) of the rat were investigated. In animals implanted previously with a lateral brain ventricle and femoral artery cannula, a single i.c.v. injection of orexin‐A (10 µg/rat) resulted in a rapid, significant increase in plasma ACTH and corticosterone concentrations. Plasma ACTH reached a peak (12.5‐fold greater than basal levels) at 30 min, which was maintained over 120 min before declining towards control levels by 240 min. Plasma corticosterone concentrations reached a peak (6.7‐fold greater than basal levels) at 30 min. Orexin‐A at a higher dose (30 µg/rat) also produced a rapid increase in plasma ACTH and corticosterone concentrations. The area under the curve for plasma levels of ACTH was similar for both doses of orexin‐A. In a second study, orexin‐A (10 µg/rat) was injected i.c.v. and brains and pituitaries were rapidly removed after 240 min. In situ hybridization histochemistry revealed that CRF and AVP mRNA levels were significantly increased in the parvocellular cells of the PVN. Pro‐opiomelanocortin mRNA levels in the pituitary gland were not significantly elevated in response to orexin‐A. These results suggest that orexin‐A is able to act centrally to activate the hypothalamic‐pituitary‐adrenal axis involving stimulation of both CRF and AVP expression.
Microinfusion of a Nitric Oxide Donor in Discrete Brain Regions Activates the Hypothalamic‐Pituitary‐Adrenal Axis
Authors: Seo D. O. , Rivier C. 
Published: March 2003

AbstractWe previously showed that the intracerebroventricular injection of the nitric oxide (NO) donor 3‐morpholino‐sydnonimine (SIN‐1) released adrenocorticotropic hormone (ACTH) and upregulated transcripts for corticotropin‐releasing factor (CRF) and vasopressin in the paraventricular nucleus (PVN) of the rat hypothalamus. In the present work, we microinfused SIN‐1 into the PVN itself, the amygdala, the hippocampus or the frontal cortex to identify the brain regions that modulate the influence of NO on the hypothalamic‐pituitary‐adrenal (HPA) axis. Microinfusion into the PVN, which contains most of the CRF and vasopressin neurones that control HPA axis activity, significantly released ACTH. Microinfusion into the amygdala or the hippocampus, areas which also regulate HPA axis activity, similarly increased plasma ACTH levels. However, these responses were smaller and showed a delayed onset, compared to that observed following PVN treatment. In contrast, microinfusion of SIN‐1 into the frontal cortex, which is not believed to exert a major direct influence on the HPA axis, was without effect. The observation that compared to microinfusion into the PVN, peak ACTH levels were both smaller and delayed when SIN‐1 was microinfused into the amygdala or the hippocampus, and that SIN‐1 only increased NO levels when injected into the PVN, suggests that the NO donor injected outside the PVN activates this nucleus by targeting pathways that connect it to these other regions rather than by leakage. Collectively, our results provide important clues regarding the putative role of these regions in modulating the influence of NO on the HPA axis.
Polyamine Regulation of the Rat Pro‐Opiomelanocortin Gene Expression in AtT‐20 Cells
Authors: Yamamori E. , Iwasaki Y. , Aoki Y. , Nomura A. , Tachikawa K. , Ariyoshi Y. , Mutsuga N. , Morishita M. , Yoshida M. , Asai M. , Oiso Y. , Saito H. 
Published: March 2003

AbstractPolyamines are a ubiquitous group of amines that play diverse biological roles. In the anterior pituitary, intracellular polyamine levels are reported to show diurnal changes, although the biological significance remains to be elucidated. In this study, we examined the effects of polyamines on the transcriptional activity of the rat pro‐opiomelanocortin (POMC) gene using AtT20PL, a clone of the AtT20 cell line in which an approximately 0.7 kb of the rat POMC 5′ promoter‐luciferase fusion gene was stably incorporated. The results showed that three representative polyamines (putrescine, spermidine and spermine) all stimulated POMC promoter activity in a time‐ and dose‐related manner, spermine showing the most potent effect (maximum approximate three‐fold increase). This effect was not observed under treatment with actinomycin D, suggesting the effect of polyamine at the transcriptional level. On the other hand, methylglyoxal bis (guanylhydrazone), an inhibitor of polyamine synthesis, showed the opposite effect, further supporting the positive role of intracellular polyamines. Taken together, our findings suggest that polyamines are involved in the regulation of POMC gene expression (especially in terms of diurnal changes) in corticotroph cells. The precise molecular mechanisms of polyamine effects await further research.
Action of Glucocorticoids on Survival of Nerve Cells: Promoting Neurodegeneration or Neuroprotection?1
Authors: Ábrahám I. M. , Harkany T. , Horvath K. M. , Luiten P. G. M. 
Published: March 2003

AbstractExtensive studies during the past decades provided compelling evidence that glucocorticoids (GCs) have the potential to affect the development, survival and death of neurones. These observations, however, reflect paradoxical features of GCs, as they may be critically involved in both neurodegenerative and neuroprotective processes. Hence, we first address different aspects of the complex role of GCs in neurodegeneration and neuroprotection, such as concentration dependent actions of GCs on neuronal viability, anatomical diversity of GC‐mediated mechanisms in the brain and species and strain differences in GC‐induced neurodegeneration. Second, the modulatory action of GCs during development and ageing of the central nervous system, as well as the contribution of altered GC balance to the pathogenesis of neurodegenerative disorders is considered. In addition, we survey recent data as to the possible mechanisms underlying the neurodegenerative and neuroprotective actions of GCs. As such, two major aspects will be discerned: (i) GC‐dependent offensive events, such as GC‐induced inhibition of glucose uptake, increased extracellular glutamate concentration and concomitant elevation of intracellular Ca2+, decrease in GABAergic signalling and regulation of local GC concentrations by 11β‐hydroxysteroid dehydrogenases; and (ii) GC‐related cellular defence mechanisms, such as decrease in after‐hyperpolarization, increased synthesis and release of neurotrophic factors and lipocortin‐1, feedback regulation of Ca2+ currents and induction of antioxidant enzymes. The particular relevance of these mechanisms to the neurodegenerative and neuroprotective effects of GCs in the brain is discussed.
Role for the Pineal and Melatonin in Glucose Homeostasis: Pinealectomy Increases Night‐Time Glucose Concentrations
Authors: La Fleur S. E. , Kalsbeek A. , Wortel J. , Van Der Vliet J. , Buijs R. M. 
Published: March 2003

AbstractThe effects of melatonin on glucose metabolism are far from understood. In rats, the biological clock generates a 24‐h rhythm in plasma glucose concentrations, with declining concentrations in the dark period. We hypothesized that, in the rat, melatonin enhances the dark signal of the biological clock, decreasing glucose concentrations in the dark period. We measured 24‐h rhythms of plasma concentrations of glucose and insulin in pinealectomized rats fed ad libitum and subjected to a scheduled feeding regimen with six meals equally distributed over the light/dark cycle and compared them with previous data of intact rats. Pinealectomy dampened the amplitude of the 24‐h rhythm in plasma glucose concentrations in rats fed ad libitum, and abolished it completely in rats subjected to the scheduled feeding regimen, while plasma insulin concentrations did not change under both conditions. Pinealectomy abolished the nocturnal decline in plasma glucose concentrations irrespective of whether rats were fed ad libitum or subjected to the scheduled feeding regimen. Melatonin replacement restored 24‐h mean plasma glucose concentrations in pinealectomized rats that were subjected to the scheduled feeding regimen but, interestingly, it did not restore the 24‐h rhythm. Melatonin treatment also resulted in higher meal‐induced insulin responses, probably mediated via an increased sensitivity of the β‐cells. Taken together, our data demonstrate that the pineal hormone, melatonin, influences both glucose metabolism and insulin secretion from the pancreatic β‐cell. The present study also demonstrates that removal of the pineal gland cannot be compensated by mimicking plasma melatonin concentrations only.
Salsolinol is a Putative Endogenous Neuro‐intermediate Lobe Prolactin‐Releasing Factor
Authors: Tóth B. E. , Homicskó K. , Radnai B. , Maruyama W. , DeMaria J. E. , Vecsernyés M. , Fekete M. I. K. , Fülöp F. , Naoi M. , Freeman M. E. , Nagy G. M. 
Published: March 2003

AbstractThe isolation and identification of a prolactin‐releasing factor (PRF) from the neuro‐intermediate lobe of the pituitary gland has been pursued for over a decade. Using high‐pressure liquid chromatography with electrochemical detection (HPLC‐ECD) and gas chromatography/mass spectrometry (GC/MS) (R)‐salsolinol (SAL) (a dopamine‐related stereo‐specific tetrahydroisoquinoline) was found to be present in neuro‐intermediate lobe as well as median eminence extracts of male, intact‐, and ovariectomized female rats. Moreover, analysis of SAL concentrations in neuro‐intermediate lobe revealed parallel increases with plasma prolactin in lactating rats exposed to a brief (10 min) suckling stimulus following 4‐h separation. SAL appears to be a selective and potent stimulator of prolactin secretion in vivo and it was without effect on the secretion of other pituitary hormones. We have also found that SAL can elevate prolactin release, although to a lesser extent, in pituitary cell cultures as well as in hypophysectomized rats bearing anterior lobe transplants under the kidney capsule. Lack of interference of SAL with [3H]‐spiperone binding to AP homogenates indicates that SAL does not act at the dopamine D2 receptor. Moreover, [3H]‐SAL binds specifically to homogenate of AL as well as neuro‐intermediate lobe obtained from lactating rats. Taken together, our data clearly suggest that SAL is synthesized in situ and this compound can play a role in the regulation of pituitary prolactin secretion.
The Affinity and Activity of the Multiple Hormone Response Element in the Proximal Promoter of the Human Oxytocin Gene
Authors: Stedronsky K. , Telgmann R. , Tillmann G. , Walther N. , Ivell R. 
Published: March 2003

Abstract In vivo there appears to be a marked association between oestrogen levels and the expression of the oxytocin (OT) gene in most tissues. Transfection and DNA‐protein binding experiments using high levels of either oestrogen receptor (ER)α or ERβ imply a direct interaction of these transcription factors with the multiple hormone response element (HRE) at approximately −160 from the transcription start site of the OT gene in most species. In an extensive set of experiments, we show, using both transfection and protein‐DNA binding, that low to moderate amounts of either oestrogen receptor, while being able to interact directly with a classic oestrogen response element (ERE) fail to interact with the human OT −160 HRE. Instead, this element, similar to its bovine counterpart, has a high affinity for the orphan receptors steroidogenic factor 1 and chicken ovalbumin upstream promoter transcription factor. Second, the human and bovine OT promoter can be made artificially responsive towards oestrogen in a cotransfection system over‐expressing ERα or ERβ, but not in cells expressing natural levels of these steroid receptors. Interestingly, nuclear extracts from both ERα‐positive MCF7 cells and ERα‐negative MDA‐MB231 cells both contain a transcription factor which binds specifically to both the hOT‐HRE element and to a classic ERE, and which has orphan receptor‐like binding properties rather than those of an oestrogen receptor. Together, these and other results suggest that oestrogen action in vivo on the OT gene in all species is more likely to involve a DNA‐independent mechanism than classic direct interactions with dimeric oestrogen receptors.
Penetration of Endogenous Steroid Hormones Corticosterone, Cortisol, Aldosterone and Progesterone into the Brain is Enhanced in Mice Deficient for Both mdr1a and mdr1b P‐Glycoproteins
Authors: Uhr M. , Holsboer F. , Müller M. B. 
Published: March 2003

AbstractNumerous investigations have confirmed an important role for multidrug‐resistance gene 1‐type P‐glycoproteins (MDR1‐type P‐gps) in the blood–brain barrier, protecting the brain against the accumulation of a wide range of toxic xenobiotics and drugs. Several studies have provided evidence in vitro that certain steroid hormones are transported by MDR1‐type P‐gps; however, the question of whether this might also apply to the situation in vivo still remained to be determined. We used mice deficient for both murine mdr1a and mdr1b P‐gps [mdr1a/1b(−/−)] to determine the uptake of [3H]‐cortisol, [3H]‐corticosterone, [3H]‐aldosterone and [3H]‐progesterone into the plasma, brain, testes, liver, spleen, pituitary and adrenal glands. We provide evidence that the access of the endogenous steroid hormones corticosterone, cortisol and aldosterone is regulated by MDR1‐type P‐gps in vivo. As peripherally administered steroid hormones accumulate in the brain of mice deficient for MDR1‐type P‐gps, mdr1a/1b proteins are likely to transport these hormones out of the brain, providing a kinetic barrier to their entry. Intracerebral progesterone concentrations are influenced by MDR1‐type P‐gp function as well; however, the effects are only small. In addition, all four endogenous glucocorticoid hormones accumulated in the testes of mdr1a/1b(−/−) mice. Our findings underline the importance of MDR1‐type P‐gps as an endogenous barrier system controlling the access of endogenous steroid hormones at the blood–brain barrier to maintain homeostatic control and to protect central nervous system neurones.
Localization of Oestrogen Receptors in the Sensory and Motor Areas of the Spinal Cord in Japanese Quail (Coturnix japonica)
Authors: Evrard H. C. , Balthazart J. 
Published: March 2003

AbstractIn Japanese quail, the presence of aromatase (oestrogen synthase) in the dorsal horn of the spinal cord suggests that spinal sensory processes might be controlled by local actions of oestrogens. This is supported by the presence of oestrogen receptors and aromatase in the dorsal horn of the spinal cord in rats, and by the alteration of sensitivity by oestrogens in various mammalian species and also in canaries. We investigated whether oestrogens that are locally produced in the quail spinal cord can bind to specific receptors in the vicinity of their site of synthesis. We demonstrate the presence of numerous oestrogen receptor α‐immunoreactive (ERα‐ir) cell nuclei, predominantly in laminae II and, to a lesser extent, I and III of the dorsal horn of the spinal cord (i.e. in the area where aromatase was previously identified). ERα‐ir cells were also seen in various parts of the intermediate zone (laminae V–VII). This presence of ERα‐ir cells in the dorsal horn and intermediate zone fits in well with the distribution of ERα‐ir cells in homologous areas in mammals, including rats. Only a few labelled cells were found in the ventral horn in the cervical, brachial, thoracic and first lumbar segments, but a conspicuous dense group of large ERα‐ir cells was identified in lamina IX of the ventral horn in synsacral segments 8–10, which contain the motoneurones innervating the muscles of the cloacal gland. The presence of ERα‐ir cells in lamina IX of these synsacral segments in quail contrasts with the finding that motoneurones innervating penile muscles in rats contain androgen, but not oestrogen receptors, and are influenced by androgens rather than by oestrogens. Together, these data suggest that spinal actions of oestrogens may modulate the sensory and motor systems that participate in reproduction, as well as other nonreproductive functions in quail.
Lipopolysaccharide Endotoxin Potentiates the Effect of Osmotic Stimulation on Vasopressin Synthesis and Secretion in the Rat Hypothalamus
Authors: Grinevich V. , Ma X.‐M. , Jirikowski G , Verbalis J. , Aguilera G. 
Published: March 2003

AbstractVasopressin secreted by magnocellular neurones of the hypothalamic supraoptic and paraventricular nuclei is essential for water balance. In this study, we examined magnocellular neurone responses to osmotic stimulation in vehicle‐injected controls or rats receiving an intraperitoneal (i.p.) injection of 250 µg/100 g of lipopolysaccharide (LPS), 3 h or 6 h earlier. LPS injection had no effect on plasma vasopressin concentrations in control rats but it caused marked and transient potentiation of the responses to a single i.p. injection of hypertonic saline (five‐ and two‐fold, 3 and 6 h after LPS, respectively). The enhancement of plasma vasopressin responses was independent of plasma sodium concentrations or changes in blood pressure. Basal vasopressin mRNA expression in the paraventricular and supraoptic nuclei decreased slightly 6 h after LPS injection, without changes in vasopressin transcription as indicated by vasopressin heteronuclear (hn) RNA levels. Parvocellular neurones showed expected increases in vasopressin hnRNA expression following LPS injection and a further increase after i.p. hypertonic saline injection (due to the painful component). In contrast to magnocellular vasopressin mRNA expression, the effects of LPS and hypertonic saline injections in parvocellular neurones were additive and not synergistic. Light microscopic immunohistochemical examination revealed an increase in size of vasopressin but not oxytocin axonal terminals in the neural lobe 3 h after LPS injection. Osmotic stimulation caused marked depletion of vasopressin immunoreactivity in axonal terminals of the neural lobe in both control and LPS‐pretreated rats. The changes in vasopressin axon terminals were accompanied by induction of interleukin (IL)‐1β and IL‐6 in the posterior pituitary. The data show that endotoxemia causes morphological and functional alterations of the hypothalamic neurohypophyseal system, resulting in facilitation rather than inhibition of vasopressin synthesis, and secretion in response to osmotic stimulation.
Effect of Intracerebroventricular Administration of the Octadecaneuropeptide on the Expression of Pro‐Opiomelanocortin, Neuropeptide Y and Corticotropin‐Releasing Hormone mRNAs in Rat Hypothalamus
Authors: Compère V. , Li S. , Leprince J. , Tonon M. C. , Vaudry H. , Pelletier G. 
Published: March 2003

AbstractIntracerebroventricular (i.c.v.) administration of the octadecaneuropeptide (diazepam‐binding inhibitor [33–50]; ODN) exerts a potent anorexigenic effect in the rat. We studied the effect of ODN on three neuropeptides involved in feeding behaviour: the orexigenic peptide neuropeptide Y (NPY) and two anorexigenic peptides, corticotropin‐releasing hormone (CRH) and the pro‐opiomelanocortin (POMC)‐derived peptide α‐melanocyte‐stimulating hormone. The effect of i.c.v. administration of ODN (0.1 µg/kg and 1 µg/kg) on mRNA expression of the peptides in male rat hypothalamus was evaluated by semiquantitative in situ hybridization. In the arcuate nucleus, NPY‐expressing neurones were mostly found in the inner zone in close proximity of the third ventricle. ODN at the dose of 0.1 µg/kg induced a significant decrease of 17.4% in NPY mRNA expression, while the depressing effect was more marked (31.4%) with the highest dose of ODN (1 µg/kg). POMC‐expressing neurones were more laterally located in the arcuate nucleus. Administration of ODN at 0.1 µg/kg and 1 µg/kg doses induced increases of 33.5% and 27.4% in POMC mRNA expression, respectively. Labelling obtained with the CRH cRNA probe was essentially distributed throughout the medial parvocellular area of the hypothalamic paraventricular nucleus. ODN, at doses of 0.1 and 1 µg/kg, resulted in 17.8% and 32.8% decreases in CRH mRNA expression, respectively. The present data suggest that ODN might exert its anorexigenic effect by increasing mRNA expression of POMC and decreasing mRNA expression of NPY in the arcuate nucleus.
The influence of war stress on the prevalence of signs and symptoms of temporomandibular disorders
Authors: Uhač I. , Kovač Z. , Valentić‐Peruzović M. , Juretić M. , Moro L. J. , Gržić R. 
Published: March 2003

summary  The aim of this study was to determine the prevalence of signs and symptoms of temporomandibular disorders in patients with post‐traumatic stress disorder (PTSD) occurring as a consequence of exposure to war stress. The examined group consisted of 100 male subjects, aged from 25 to 50 years, who had taken part in the War in Croatia, and in whom PTSD had previously been diagnosed. The control group comprised 100 subjects, without PTSD, of the same sex and age group, who had not taken part in the War. A functional evaluation of the stomatognathic system was performed using the Helkimo Anamnestic and Clinical Dysfunction Index.Eighty‐two per cent of the group with PTSD had at least one symptom, and 98% at least one sign of dysfunction. Eight per cent reported mild symptoms and 74% severe symptoms. Twenty‐eight per cent showed mild clinical signs, 22% had signs of moderate, and 48% of severe dysfunction.Twenty‐four per cent of the control group of subjects had at least one symptom, and 52% at least one clinical sign of dysfunction. Twenty‐two per cent reported mild and 2% severe symptoms. Mild clinical signs of dysfunction were found in 50% of subjects in the control group, moderate in 2% and none exhibited severe clinical signs. It is concluded that correlation exists between war stress and temporomandibular disorders.
Simple reaction time, duration of driving and sleep deprivation in young versus old automobile drivers
Authors: PHILIP P. , TAILLARD J. , QUERA‐SALVA M. A. , BIOULAC B. , ÅKERSTEDT T. 
Published: March 2003

SummaryCar accidents are one of the major causes of death in modern society and sleepiness is identified as one major risk factor. The purposes of the present study were: (1) to relate the sleep loss and driving time to a performance indicator and (2) to identify risk factors of performance decrement. We investigated 294 drivers (age < 30 years, n=100; age ≥ 30 years, n=194) who drove into a rest stop area. All were asked to fill out a questionnaire about the drive and previous sleep/wake pattern, and to carry out a 10 min, simple reaction time (RT) test. The level of performance is identified by the 10% slowest RTs. Multiple regression analysis, with the mean of the 10% Slowest RTs as the dependent variable, showed that age, duration of drive, and duration (shortness) of previous breaks were the main predictors. Our study suggests that public awareness may need to be raised with respect excessive length of driving, especially in young drivers.