bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of Substance P‐immunoreactivity by Estrogen in Neurons Containing Estrogen Receptors in the Anterovental Periventricular Nucleus of Female but not Male Rats
Authors: Okamura Hiroaki , Yokosuka Makoto , Hayashi Shinji 
Published: September 2006

AbstractEffects of gonadal steroids on numbers of neurons containing estrogen receptor (ER) and/or substance P (SP) were examined in the anteroventral periventricular nucleus (AVPV) of female and male rats by double‐labeling immunohistochemistry employing antibodies specific for ER and SP. Animals were gonadectomized and received subcutaneously either oil alone (Control group), sequential injections of estradiol benzoate and oil (EB + Oil group), or those of EB and progesterone (EB + P group). In the female control rat, a large population of ER‐immunoreactive (IR) cells were found clustered throughout the AVPV. They were counted more than 2,000 in total of 4 sections in this nucleus. On the contrary, SP‐IR neurons were scarcely observed in the same area of this group. Administration of estrogen to female animals decreased the total number of ER‐IR cells to 67% of the control group. In contrast to the supressive effect of estrogen to its own receptor, it induced SP‐IR neurons in the AVPV of the female. Approximately 50–80 SP‐IR neurons were counted in the 4 sections, and 59% of these neurons expressed ER‐IR material in their nuclei. In the female EB + P group, the number of ER‐IR neurons also decreased to 79% of the control group. Although the number of SP‐IR neurons in this group decreased to 32% of that in the EB + Oil group, a ratio of coexistence of ER‐IR material in these neurons increased to 75%. The male control group contained a smaller population of ER‐IR cells relative to the female control (1497 vs 2143). SP‐IR neurons were rarely observed as were in the female control. Administration of estrogen to the male also decreased the number of ER‐IR cells in a manner similar to that in the female. However, unlike the female, the steroid failed to induce the SP‐IR neurons in the male.These results demonstrate sexual dimorphism in the AVPV not only in the number of ER‐IR neurons but also in the responsiveness of SP neurons to estrogen. They further provide anatomical evidence that a subset of SP neurons are regulated by estradiol in estrogen sensitive neurons in the female rat. The data also suggest that this peptide is involved in mechanisms of luteinizing hormone surge by mediating actions of gonadal steroids in the AVPV.
Glucocorticoid Regulation of c‐fos, c‐jun and Transcription Factor AP‐1 in the AtT‐20 Corticotrope Cell
Authors: Autelitano Dominic J. 
Published: September 2006

AbstractGlucocorticoids (GC) are potent repressers of both basal and corticotropin releasing factor (CRF) stimulated transcription of the proopiomelanocortin (POMC) gene in corticotrope cells of the anterior pituitary. Despite the finding of a novel, high affinity glucocorticoid receptor (GR) binding site within the proximal region of the POMC promoter, the mechanism by which GC inhibit POMC transcription is still uncertain. Recent studies have described mechanisms whereby GC inhibit transcription of other genes via a direct interaction with components of the transcription factor AP‐1. Since it has been shown that CRF stimulates c‐fos in AtT‐20 corticotrope cells, and that c‐fos over‐expression elevates POMC transcription, the current study has investigated whether GC can repress c‐fos and c‐jun gene expression and AP‐1 DMA binding activity in AtT‐20 corticotrope cells. Acute treatment with doses of dexamethasone (DEX) that markedly inhibited nuclear POMC hnRNA had no effect on basal c‐fos mRNA expression, but resulted in a transient down regulation of c‐jun. In addition, acute DEX pretreatment significantly lowered CRF stimulation of POMC gene expression and attenuated the CRF stimulation of c‐fos mRNA by 25%. Although DEX treatment of AtT‐20 cells did not affect AP‐1 DNA binding capacity of nuclear extracts, DEX pretreatment blunted the stimulation of AP‐1 binding in response to CRF. In further studies, nuclear extracts from CRF‐treated cells were coincubated with nuclear extracts from control or DEX treated cells. High levels of DEX treated extracts led to a relative repression of CRF‐induced AP‐1 binding, suggesting that ligand‐activated GR may lower available AP‐1 levels by direct protein: protein interaction. Finally, the composition of AP‐1 in AtT‐20 nuclear extracts was found to be heterogeneous, with the variation dependent upon hormonal treatment. These data suggest that in the corticotrope cell relatively high levels of activated GR may influence CRF‐induced AP‐1 DNA binding via transient genomic actions on basal c‐jun and stimulated c‐fos and/or via direct protein: protein interactions.
Endogenous Glucocorticoids and the Induction and Spread of Monoarthritis in the Rat
Authors: Donaldson Lucy F. , McQueent Daniel S. , Seckl Jonathan R. 
Published: September 2006

AbstractUsing mono ‐ and bilateral tarsal arthritic models in the rat, we have previously shown increases in the expression of mRNAs encoding substance P and calcitonin gene‐related peptide (CGRP) in primary sensory neurons innervating inflamed joints. Dorsal root ganglion (DRG) neuropeptide content in rats is altered by glucocorticoids, and since glucocorticoids regulate the expression of preprotachykinin (PPT) gene, the substance P precursor in other tissues, these effects may be mediated at the level of transcription. Indeed adrenalectomy potentiates disease in polyarthritis although the relationship to joint disease itself is unclear. Secretion of corticosterone in both mono ‐and bilaterally inflamed rats showed a loss of the normal diurnal nadir with no elevation of evening values. However, there were no changes in glucocorticoid target organs (adrenal gland, thymus and spleen) suggesting the stress was intermittent. Adrenalectomy in mono ‐ and bilaterally inflamed rats did not significantly alter either the severity of inflammation or its spread. Bilaterally inflamed animals did, however, show reduced weight gain. Adrenalectomy had no effect on the induction of PPT and CGRP mRNA expression in innervating DRG neurons in monoarthritis (14 days after adjuvant injection), the unilateral increase in both PPT and CGRP mRNA expression in ADX animals being similar to SHAM arthritic rats. (PPT: ADX 140 ± 13 left; 99 ± 6 right % control; SHAM 160 ± 22 left, 100 ± 5 right % control. CGRP: ADX 177 ± 6 left, 97 ± 3 right % control; SHAM 147 ± 21 left, 100 ± 5 right % control). In bilaterally arthritic rats adrenalectomy potentiated the increase in CGRP mRNA expression (SHAM 168 ± 6% left, 271 ± 23% right; ADX 217 ± 38% left, 193 ± 4% right; control 100 ± 5%) but significantly attenuated the contralateral (right) increase in PPT mRNA expression seen in sham‐operated rats (SHAM 136 ± 21% left; 140 ± 11% right; ADX 145 ± 28% left, 86 ± 15% right; control 100 ± 5%). Inflammation‐associated changes in somatostatin mRNA expression were similar in sham‐operated and adrenalectomized rats. We conclude, therefore, that whilst adrenalectomy exerts subtle effects on the expression of PPT and CGRP mRNAs in DRG neurons in bilateral arthritis, the presence or absence of high circulating endogenous corticosteroids in these animals, with limited arthritis, do not modulate the arthritic process.
Detection of Neutral Endopeptidase (NEP, Enkephalinase, E.C.3.4.24.11) in Relation to Dopaminergic and Gonadoliberinergic Nerve Endings in the Median Eminence of the Male Rat: A Double Labeling Ultrastructural Study
Authors: Vandenbulcke Franck , Ciofi Philippe , Beauvillain Jean Claude 
Published: September 2006

AbstractThe existence of neutral endopeptidase (Enkephalinase, NEP, E.G.3.4.24.11) in membranes of nerve endings in the rat median eminence suggests that some neuropeptides have paracrine and/or autocrine actions in this region. In vitro, neutral endopeptidase is capable of hydrolysing a variety of regulatory peptides but in vivo, many works indicate that in the central nervous system this enzyme is highly implicated in the biological inactivation of enkephalins and tachykinins. In addition there is evidence that NEP is also involved in the inactivation of neurotensin in vivo.The modulation of the release of gonadotrophin releasing hormone (GnRH) is one of the documented actions of enkephalins within the median eminence. However, it is at present unclear whether enkephalins act on dopamine endings, on GnRH endings or on both.As the technical parameters and particularly the tissue fixation used to detect neutral endopeptidase are compatible with immunocytochemical detection of GnRH and tyrosine‐hydroxylase (the rate limiting enzyme in the synthesis of catecholamines), two double immunolabelings were realised at the ultrastructural level to determine if GnRH and dopamine nerve endings have the enzyme inserted within their plasma membrane.Our study shows the presence of neutral endopeptidase on tyrosine‐hydroxylase‐immunoreactive nerve endings while presence of the enzyme on GnRH‐immunoreactive nerve endings is not demonstrated. Consequently, our results provide morphological arguments for possibilities of paracrine and/or autocrine actions by neuropeptides inactivated by neutral endopeptidase on tuberoinfundibular dopa‐minergic nerve endings. Conversely, action of the same peptides on GnRH boutons seems more unlikely.
Adenylyl Cyclase mRNA Expression does not Reflect the Predominant Ca2+/Calmodulin‐Stimulated Activity in the Hypothalamus
Authors: Mons Nicole , Cooper Dermot M. F. 
Published: September 2006

AbstractOnly three (Types I, II, V) of the six currently‐described subtypes of adenylyl cyclase are prominently expressed in the rat brain. These species are differently sensitive to Ca2+, βγ subunits of G‐proteins and protein kinase C. A knowledge of the susceptibility of the cAMP‐signalling system in particular brain regions to these diverse modes of regulation can shed light on the mechanism of action of the neurotransmitters that modify neuronal activity in such regions. Cyclic AMP is extensively involved in the physiological functions of the hypothalamus. We have used in situ hybridization histochemistry with synthetic oligonucleotides to examine the expression in the rat hypothalamus of the three major brain subtypes of adenylyl cyclase‐Ca2+/calmodulin‐stimulable (Type I), Ca2+‐insensitive (Type II) and Ca2+ ‐inhibitable (Type V). The hypothalamus expresses high levels only of Type II mRNA, particularly in the supraoptic and paraventricular nuclei. Curiously, the strong expression of the Ca2+‐insensitive Type II mRNA and the lack of expression of the major brain specific Type I mRNA does not correlate with the adenylyl cyclase activity, which is largely Ca2+/calmodulin stimulable in plasma membranes prepared from the hypothalamus.
Stress‐Specific Regulation of Corticotropin Releasing Hormone Receptor Expression in the Paraventricular and Supraoptic Nuclei of the Hypothalamus in the Rat
Authors: Luo Xun , Kiss Alexander , Makara Gabor , Lolait Stephen J , Aguilera Greti 
Published: September 2006

AbstractCorticotropin releasing hormone (CRH), a major regulator of pituitary ACTH secretion, also acts as a neurotransmitter in the brain. To determine whether CRH is involved in the regulation of hypothalamic function during stress, CRH receptor binding and CRH receptor mRNA levels were studied in the hypothalamus of rats subjected to different stress paradigms: immobilization, a physical‐psychological model; water deprivation and 2% saline intake, osmotic models; and i.p. hypertonic saline injection, a combined physical‐psychological and osmotic model. In agreement with the distribution of CRH receptor binding in the brain, in situ hybridization studies using 35S‐labeled cRNA probes revealed low levels of CRH receptor mRNA in the anterior hypothalamic area, which were unaffected after acute or chronic exposure to any of the stress paradigms used. Under basal conditions, there was no CRH binding or CRH receptor mRNA in the supraoptic (SON) or paraventricular (PVN) nuclei. However, 2 h after the initiation of acute immobilization, CRH receptor mRNA hybridization became evident in the parvicellular division of the PVN, with levels substantially increasing from 2 to 4 h, decreasing at 8 h and disappearing by 24 h. Identical hybridization patterns of CRH receptor mRNA were found in the parvicellular PVN after repeated immobilization; levels were similar to those after 2 h single stress following immobilization at 8‐hourly intervals for 24 h (3 times), and very low, but clearly detectable 24 h after 8 or 14 days daily immobilization for 2 h. On the other hand, water deprivation for 24 or 60 h and intake of 2% NaCI for 12 days induced expression of CRH receptor mRNA in the SON and magnocellular PVN, but not in the parvicellular pars of the PVN. Both parvicellular and magnocellular hypothalamic areas showed CRH receptor mRNA following i.p. hypertonic saline injection, single (4 h after) or repeated at 8‐hourly intervals for 24 h (3 injections), or one injection daily for 8 or 14 days. Consistent with the expression of CRH receptor mRNA, autoradiographic studies showed binding of 125I‐Tyr‐oCRH in the parvicellular division of the PVN after immobilization; in the magnocellular division of the PVN after osmotic stimulation, and in the PVN and SON after i.p. hypertonic saline injection. The data show that stress‐specific activation of the parvicellular and magnocellular systems is associated with CRH receptor expression, and suggest a role for CRH in the autoregulation of hypothalamic function.
Limbic Regions Mediating Central Actions of Oxytocin on the Milk‐Ejection Reflex in the Rat
Authors: Ingrarn C. D. , Adams T. S. T. , Jiang Q. B. , Terenzi M. G. , Lambert R. C. , Wakerley J. B. , MOOS F. 
Published: September 2006

AbstractCentral oxytocin administration has a profound facilitatory effect on the patterning of the milk‐ejection reflex in the lactating rat. Lesion and microinjection studies indicate that this action is, in part, mediated via a population of limbic neurones in the bed nuclei of the stria terminalis and ventrolateral septum, which have been shown to possess oxytocin receptors and to be activated by selective oxytocin‐receptor agonists in vitro. In vivo electro‐physiological recordings reveal that some of these neurones display cyclical activity which is highly correlated to each milk ejection, and are rapidly activated following i.c.v. administration of oxytocin. coincident with the facilitation of milk ejection activity. A hypothetical model is proposed in which this population of limbic neurones serves to gate the activity of a pacemaker which, in turn, coordinates the bursting of hypothalamic magnocellular neurones. The oxytocin innervation of these neurones and their expression of oxytocin receptors increases in the post‐partum period, and the resultant enhanced sensitivity leads to a greater facilitatory response during lactation. Inhibitory opioid and noradrenergic inputs which converge on these oxytocin‐sensitive neurones may function to switch off the facilitatory circuit during periods of stress. Thus, this population of limbic neurones participates in the regulation of neuroendocrine activity during lactation by providing an appropriate degree of feedback to alter the patterning of the milk‐ejection reflex.
Naloxone Disinhibits Magnocellular Responses to Osmotic and Volemic Stimuli in Chronically Hypoosmolar Rats
Authors: Dohanics Janos , Verbalis Joseph G. 
Published: September 2006

AbstractNormonatremic and chronically hyponatremic rats were pretreated with naloxone (5 mg/kg) or isotonic (1 50 mM) NaCI, then were given i.v. injections of 2 M NaCl (2 ml) or were hemorrhaged (20 ml/kg). Baseline and post‐stimulus blood samples were withdrawn through indwelling jugular venous catheters. Baseline levels of plasma vasopressin (AVP) and oxytocin (OT) were similar in both normonatremic and hyponatremic rats and did not change after naloxone pretreatment. Increases in plasma AVP and OT levels in response to both hypertonic saline and hemorrhage were markedly blunted in the hyponatremic rats compared to the normonatremic rats. Naloxone pretreatment caused augmented AVP and OT secretion in response to hypertonic saline stimulation and hemorrhage in both the normonatremic and hyponatremic rats; the magnitude of the naloxone augmentations in the hyponatremic rats were sufficient to normalize the OT response to hypertonic saline and both the OT and AVP responses to hemorrhage. Our results therefore suggest that endogenous opioids are likely involved in the inhibition of stimulus‐induced AVP and OT release that accompanies chronic hypoosmolality.
Hypothalamic Site‐Dependent Effects of Neuropeptide Y on Gonadotropin‐Releasing Hormone Secretion in Rhesus Macaques
Authors: Francis Pau K.‐Y. , Berria Matthew , Hess David L. , Spies Harold G. 
Published: September 2006

AbstractIn rodents and rabbits, neuropeptide Y (NPY) has a bimodal effect on gonadotropin‐releasing hormone (GnRH) secretion. lntracerebroventricular (icv) administration or direct infusion of NPY into the median eminence (ime) suppresses GnRH release in ovariectomized (OVX) animals, but stimulates GnRH release in intact or OVX animals treated with ovarian steroids. Specific ovarian steroiddependent NPY effects are, however, not obvious in non‐human primates. In OVX rhesus monkeys, icv administration of NPY has been shown to suppress luteinizing hormone (LH) secretion whereas ime infusion of NPY stimulates GnRH pulses. In such animals, estrogen replacement does not reverse the inhibitory NPY effect on LH release, although estrogen enhances the stimulatory NPY effect on GnRH secretion. These observations led us to speculate that the bimodal NPY effects in non‐human primates may depend on either the site of NPY action or the nature of the steroid milieu. This study utilized the push‐pull perfusion (PPP) technique to examine the effects of either ime or icv infusion of NPY on GnRH release in OVX monkeys treated with or without both ovarian steroids. Without exception, irne infusion of NPY increased GnRH concentrations in push‐pull perfusates regardless of the steroid status of the animals. In contrast, GnRH levels were reduced during icv infusion of NPY in both untreated and estrogen/progesterone‐treated, OVX monkeys. These results indicate that, unlike other mammalian species, in the rhesus monkey the stimulatory and inhibitory effects of NPY on GnRH release depend on the site of NPY infusion within the brain rather than the ovarian steroidal environment.
The Effect of Long‐Term Castration on the Neuronal and Physiological Responses to Acute or Repeated Restraint Stress: Interactions with Opioids and Prostaglandins
Authors: Chen Xihua , Herbert J. 
Published: September 2006

AbstractSixty min supine restraint stress induced a marked, but transient, hypothermic response in intact male rats, which tended to recover towards pre‐stress levels or slightly overshoot during the later stages of restraint. Castration reduced the initial hypothermia but increased overshoots. Baseline (pre‐stress) core temperature was also higher in castrated than intact rats, but the reduction in stress‐induced hypothermia was still present even when this difference had been taken into account. The hypothermic response was not altered during the course of 10 sessions of daily repeated restraint in either intact or castrated rats. Castration did not alter cardiac responses to restraint. Both intact and castrated rats showed marked tachycardia during the initial 12 min of restraint, followed by a gradual fall towards baseline values. Repeated restraint accentuated the second phase of the cardiac response, without modifying the initial tachycardia, in both intact and castrated animals. The response of blood corticosterone levels to the first period of restraint was unaltered by castration but the attenuation observed after 10 sessions of stress was more complete in castrated rats.The neuronal c‐fos response 60 min after the last of the series of repeated restraints was less in the hypothalamic paraventricular nucleus, medial amygdala, and locus coeruleus compared with that following the first session, but not in the lateral septum or the bed nucleus of the stria terminalis. Castration did not change the c‐fos profile following the same number of restraint sessions. Castration depleted completely the vasopressinergic innervation in the lateral septum, diagonal band of Broca and medial amygdala.Five mg/kg naloxone i.p. prior to the onset of stress resulted in persistent hypothermic responses throughout the stress period in intact males. This was reduced in castrated rats. Blockade of prostaglandins synthesis by 12 mg/kg indornethacin i.p. 3 h prior to stress had little effect on hypothermic stress responses.The results of these experiments suggest that an androgen‐dependent process, possibly AVP‐containing systems in the forebrain, may regulate both baseline and stress‐induced levels of core temperature and have selective effects on components of the response to stress, including restraint‐induced hypothermia and the adaptation of corticoid responses to repeated restraint. Steroid‐dependent opioid systems may also be implicated in the hypotherrnic response to restraint stress.
Bilateral Lesions of the Suprachiasmatic Nuclei Alter the Nocturnal Melatonin Secretion in Sheep
Authors: Tessonneaud A. , Locatelli A. , Caldani M. , Viguier‐Martinez M. C. 
Published: September 2006

AbstractThe hypothalamic suprachiasmatic nuclei (SCN) constitute both the biological clock of many circadian rhythms, and the first relay in the transmission of light cues from the retina to the pineal gland, which releases, via nocturnal melatonin secretion, an endocrine expression of the daylength. The aim of the present work was to investigate the precise role of the SCN in the entrainment of the nocturnal rhythm of melatonin (MEL) in sheep. Bilateral lesions of the SCN were performed via a transsinusal surgical approach in 10 adult rams submitted to a constant photoperiod (16L:8D). Lesioned rams were compared to 4 sham and 2 control animals. Blood samples were collected 8 days before, 8 days after, and one month after surgery. Plasma MEL levels were estimated using direct radioimmunoassay. At the end of the experiment, histology and immunohistochemistry of the suprachiasmatic area were performed, and the extent of lesions was evaluated using a computerized image analysis system. Six rams exhibited a complete lesion of the SCN, and in the four remaining animals, the lesions were restricted to the anterior part of the SCN. For all animals, the nocturnal melatonin secretion was altered, but depending on the extent of the lesion, two types of results were observed:Eight days after surgery, in 3 of the 4 rams bearing anterior lesions of the SCN (SCNJ, a nocturnal increase in melatonin secretion still occurred at dusk, but the duration of this secretion extended beyond the end of the night. One month after surgery, melatonin profiles were once again normal, as compared to sham animals. The fourth SCN, ram exhibited a cyclic MEL secretion not synchronized with the light cycle 8 days after surgery, and synchronized with dusk but not dawn one month after surgery.Eight days after surgery, all the rams bearing complete lesions of the SCN (SCNZ) showed strongly altered MEL secretion. This secretion was continuous during the period of sampling, without any characteristic nocturnal peak. Nevertheless, one month after surgery, a nocturnal increase in melatonin secretion synchronized with the dusk was again observed, but the duration of the melatonin secretion was longer than the duration of the night.These results confirm that the SCN mediates the nocturnal pineal gland activity, demonstrate that the anterior part of the sheep SCN is the main drive for the inhibition of the melatonin secretion at dawn and suggest that a positive input to the pineal gland may stimulate MEL secretion at dusk. The partial recovery of the cyclic secretion of melatonin after complete lesioning of the SCN suggests the existence of other structure(s) involved in this rhythmic function.