bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of the Post‐Translational Processing of Chromogranin A in Rat Neuroendocrine Tissue Employing an N‐Terminal Site‐Specific Antiserum
Authors: McVicar C. M. , Cunningham R. T. , Harriott P. , Johnston C. F. , Buchanan K. D. , Curry W. J. 
Published: March 2003

AbstractChromogranin A (CgA) is a complex prohormone expressed as a constituent of the regulated secretory pathway of numerous neuroendocrine cells. Recent investigations have demonstrated that CgA is selectively cleaved to generate distinct peptides in different neuroendocrine tissues. This investigation employed a site‐specific antiserum that detects residues 98–106 rat CgA to examine the amino‐terminal processing of CgA to generate β‐granin and related peptides in rat neuroendocrine tissues. Immunohistochemistry revealed moderate to intense β‐granin‐like immunostaining in cells scattered throughout the anterior pituitary, thyroid, in the islets of Langerhans and in the mucosa of the gastrointestinal tract. Variable intensities of immunostaining were observed in distinct clusters of chromaffin cells. Quantitatively, the highest concentration of β‐granin‐like immunoreactivity was detected in pituitary extracts. Significantly lower concentrations were detected in adrenal and thyroid glands, brain, ventral and dorsal pancreatic lobes and gastrointestinal tissue extracts. Chromatography resolved three distinct β‐granin‐like immunoreactants; a large CgA‐like form, an intermediate molecular form presumably corresponding to β‐granin (rat CgA1−128) and small immunoreactants that coeluted with the synthetic peptide. Two β‐granin‐like immunoreactants, 21 and 22 kDa, were detected following immunoblot analysis of pituitary extracts. This study has demonstrated that chromogranin A is subject to distinct amino‐terminal patterns of tissue‐and cell‐specific processing to generate a β‐granin‐like immunoreactant which is additionally cleaved in pancreatic, fundic and colonic tissue to generate previously unidentified peptides.
Antagonism of Central Vasopressin Receptors Blocks Hypoglycemic Stress Induced Inhibition of Luteinizing Hormone Release in Male Rhesus Macaques
Authors: Lado‐Abeal J. , Clapper J. A. , Norman R. L. 
Published: March 2003

AbstractThe first objective of this study was to investigate whether the inhibitory effect of insulin‐induced hypoglycemia (IIH) on luteinizing hormone (LH) secretion was the same in unrestrained adult male rhesus macaques as has been previously reported in restrained female macaques. Since IIH did inhibit pulsatile LH secretion in adult male macaques, and some previous studies have implicated arginine vasopressin (AVP) as a central mediator of this inhibition, the second objective was to investigate whether antagonism of AVP action could reverse the IIH‐induced inhibition of LH release in males. Ten adult male rhesus macaques (Macaca mulatta) were studied during 15‐h periods (07.00–22.00 h), with blood samples collected every 15‐min. There were three experimental groups; controls (n = 5), IIH (n = 6) and IIH plus vasopressin antagonist (AVPa; n = 6). During the hypoglycemia studies, the first 5 h served as a control for that occasion and an insulin bolus of 1 U/kg was administered intravenously at 12.00 h. During the IIH plus AVPa, the vasopressin antagonist was infused intravenously from 12.00 h to 17.00 h. LH and testosterone decreased progressively after the insulin bolus in the IIH group reaching a minimum value at 4 h after the infusion. However, compared to the preinfusion levels, secretion of LH and testosterone was not suppressed by hypoglycemia in the group treated with the AVP antagonist. The present study shows that in male macaques not subjected to the psychological stress of restraint, IIH suppresses LH and testosterone secretion. This inhibition of LH release can be blocked in some animals by antagonism of central vasopressin receptors, suggesting that vasopressin is involved in the suppression of gonadotropin releasing hormone/LH release induced by hypoglycemia.
Absence of Androgen Receptor in the Growth Hormone Releasing Hormone‐Containing Neurones in the Rat Mediobasal Hypothalamus
Authors: Fodor M. , Oudejans C. B. M. , Delemarre‐van de Waal H. A. 
Published: March 2003

AbstractGrowth hormone (GH) secretory patterns are influenced by gonadal steroids, at least in part, through modulation of hypothalamic somatostatin and GH releasing hormone (GHRH) secretion. In the adult male rat, testosterone appears to stimulate somatostatin gene expression by acting directly on androgen receptors in somatostatin neurones. The mechanism by which gonadal status influences hypothalamic GHRH gene expression is less clear. Gonadectomy reduces GHRH mRNA expression in rats, and this reduction can be prevented by the administration of testosterone or partly by a nonaromatizable androgen. While these observations suggest that androgen receptors mediate the actions of gonadal steroids on GHRH gene expression, they do not provide any information about the location of the androgen receptors involved in this process. To determine whether GHRH neurones themselves express androgen receptors, we double immunolabelled hypothalamic sections from colchicine‐pretreated male rats. Although there was an overlap in the anatomical distribution of GHRH and androgen receptor‐containing cell bodies, none of the nearly 900 GHRH immunolabelled cells we examined in each mediobasal hypothalamus appeared to contain androgen receptors. These results suggest that GHRH‐expressing neurones are not direct targets for androgens and therefore the effects of testosterone on GHRH gene expression must be produced indirectly by some other neural or endocrine intermediary process.
Crosstalk Between Oestrogen Receptors and Thyroid Hormone Receptor Isoforms Results in Differential Regulation of the Preproenkephalin Gene
Authors: Vasudevan N. , Zhu Y.‐S. , Daniel S. , Koibuchi N. , Chin W. W. , Pfaff D. 
Published: March 2003

AbstractNuclear receptors are ligand‐activated transcription factors, which have the potential to integrate internal metabolic events in an organism, with consequences for control of behaviour. Previous studies from this laboratory have shown that thyroid hormone receptor (TR) isoforms can inhibit oestrogen receptor (ER)α‐mediated induction of preproenkephalin (PPE) gene expression in the hypothalamus. Also, thyroid hormone administration inhibits lordosis, a behaviour facilitated by PPE expression. We have examined the effect of multiple ligand‐binding TR isoforms on the ER‐mediated induction of the PPE gene in transient transfection assays in CV‐1 cells. On a natural PPE gene promoter fragment containing two putative oestrogen response elements (EREs), both ERα and β isoforms mediate a four to five‐fold induction by oestrogen. Cotransfection of TRα1 along with ERα inhibited the ERα transactivation of PPE by approximately 50%. However, cotransfection with either TRβ1 or TRβ2 expression plasmids produced no effect on the ERα or ERβ mediated induction of PPE. Therefore, under these experimental conditions, interactions with a single ER isoform are specific to an individual TR isoform. Transfection with a TRα1 DNA‐binding mutant could also inhibit ERα transactivation, suggesting that competition for binding on the ERE may not be the exclusive mechanism for inhibition. Data with the coactivator, SRC‐1, suggested that coactivator squelching may participate in the inhibition. In dramatic contrast, when ERβ is cotransfected, TRα1 stimulated ERβ‐mediated transactivation of PPE by approximately eight‐fold over control levels. This is the first study revealing specific interactions among nuclear receptor isoforms on a neuroendocrine promoter. These data also suggest that the combinatorics of ER and TR isoforms allow multiple forms of flexible gene regulations in the service of neuroendocrine integration.
Centrally Regulated Blood Pressure Response to Vasoactive Peptides is Modulated by Corticosterone
Authors: Van Acker S. A. B. E. , Oitzl M. S. , Fluttert M. F. J. , De Kloet E. R. 
Published: March 2003

AbstractTo investigate the role of brain glucocorticoid (GR) and mineralocorticoid receptors (MR) in centrally evoked blood pressure responses, the effects of intracerebroventricular (i.c.v.) administration of angiotensin II and vasopressin were studied in adrenalectomized rats with and without corticosterone or aldosterone replacement. Five groups were examined: (i) Adrenalectomy (ADX); (ii) ADX + a subcutaneously implanted 20‐mg corticosterone pellet (low corticosterone); (iii) ADX + 100 mg corticosterone pellet (high corticosterone); (iv) ADX + 6 µg/24 h aldosterone via Alzet minipump (Aldo); and (v) Sham adrenalectomy (Sham). Pressor responses to 150 ng angiotensin II and 50 ng vasopressin i.c.v. were determined in freely moving rats using biotelemetry. The results show that, compared to sham rats, ADX rats showed significantly reduced pressor responses. This reduction of the pressor response to angiotensin II could be reversed and even further enhanced by replacement of the ADX rats with high corticosterone concentrations. In contrast, with aldostosterone, a depressor type response was observed. Corticosterone replacement could not restore the pressor response to vasopressin. We conclude that the pressor response to centrally administered vasoactive substances is substantially attenuated by removal of the adrenals and that, in the case of angiotensin II, this is due to the lack of high concentrations of circulating corticosterone occupying both MR and GR. However, predominant MR occupancy appears to play an opposite role and attenuates the angiotensin II‐induced pressor response.
Maternal Regulation of the Hypothalamic‐Pituitary‐Adrenal Axis in the 20‐Day‐Old Rat: Consequences of Laboratory Weaning
Authors: Schmidt M. , Okimoto D. K. , Dent G. W. , Gordon M. K. , Levine S. 
Published: March 2003

AbstractThere is a large body of evidence that the development of the hypothalamic‐pituitary‐adrenal (HPA) system in the rat is under maternal regulation. One method used to study the influence of the dam–pup interaction in neonates and weanlings is the separation of mother and litter for 24 h. Previous studies showed that, even at the time of weaning, maternal deprivation results in a dysregulation of the HPA axis at multiple levels. However, the maternal deprivation paradigm usually includes deprivation of food and water, and it was not clear to which extent the observed effects are due to either maternal cues or dehydration and fasting. The primary purpose of the present study was to determine the role of fasting and/or maternal separation on the HPA axis at the time of weaning. Pups at 20 days after parturition are capable of self‐feeding and no longer require tactile stimulation to induce eliminative functions. The results indicated that 24 h of fasting led to increased basal levels and further increases in stress induced corticosterone secretion. Fasting also appeared to contribute to the down regulation of basal glucocorticoid receptor mRNA in the hippocampus. In contrast, abrupt weaning irrespective of fasting or dehydration resulted in a suppressed adrenocorticotropin hormone response to an injection of isotonic saline. Although there was an effect of maternal separation on corticotropin‐releasing factor mRNA in the paraventricular nucleus, this effect was further exacerbated by the absence of food. Finally, all rats that were separated from their dams showed more efficient negative‐feedback. Thus, different aspects of the HPA system appear to respond differentially to either the absence of food or the absence of the mother or both.
Vasoactive Intestinal Polypeptide Contacts on Gonadotropin‐Releasing Hormone Neurones Increase Following Puberty in Female Rats
Authors: Kriegsfeld L. J. , Silver R. , Gore A. C. , Crews D. 
Published: March 2003

AbstractSuccessful reproduction requires precise temporal coordination among various endocrine and behavioural events. The circadian system regulates daily temporal organization in behaviour and physiology, including neuroendocrine rhythms. The main circadian pacemaker in mammals is located in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. The SCN sends direct efferents to the reproductive axis via monosynaptic projections to gonadotropin‐releasing hormone (GnRH) neurones. This communication generates circadian endocrine rhythms as well as the preovulatory luteinizing hormone (LH) surge necessary for successful ovulation. One SCN peptide thought to be important for the regulation of oestrous cycles is vasoactive intestinal polypeptide (VIP). VIP neurones from the SCN contact GnRH cells, and these cells are preferentially activated during an LH surge in rats. Unlike adult rats, prepubertal females do not exhibit oestrous cycles, nor do they exhibit an LH surge in response to oestradiol positive‐feedback. The present study was undertaken to determine the extent to which the development of a ‘mature’ reproductive axis in female rats is associated with modifications in VIP contacts on GnRH neurones. The brains of diestrus adult (approximately 60 days of age) and prepubertal (21 days of age) female rats were examined using double‐label fluorescence immunohistochemistry for VIP and GnRH, with light and confocal microscopy. Although the total number of GnRH‐immunoreactive neurones did not differ between adult and prepubertal females, adults had a significant increase in the percentage of GnRH cells receiving VIP contacts compared to juveniles. These data suggest that the development of reproductive hormone rhythms and oestrous cyclicity may be, in part, due to modifications of VIP input to the GnRH system.
Plasma Agouti‐Related Protein Level: A Possible Correlation with Fasted and Fed States in Humans and Rats
Authors: Shen C.‐P. , Wu K. K. , Shearman L. P. , Camacho R. , Tota M. R. , Fong T. M. , Van der Ploeg L. H. T. 
Published: March 2003

AbstractWe measured plasma concentrations of agouti‐related protein (AGRP) in humans and rats and determined whether these were affected by ingestion of a meal after fasting. In 17 healthy human subjects, the mean plasma concentration of AGRP was lower in the fed state than in the fasted state. Two hours after a breakfast meal, AGRP levels dropped by 39%. By contrast, a continued fast for 2 h increased the average AGRP concentration by 73%. In rats with diet‐induced obesity, refeeding resulted in a 50% decrease in plasma AGRP concentrations following a fasting‐refeeding protocol. Our results support the notion that plasma AGRP may serve as a biomarker for the transition from a fasted to the satiated state.
Lamprey Gonadotropin Hormone‐Releasing Hormone‐III has No Selective Follicle‐Stimulating Hormone‐Releasing Effect In Rats
Authors: Kovacs M. , Seprodi J. , Koppan M. , Horvath J. E. , Vincze B. , Teplan I. , Flerko B. 
Published: March 2003

AbstractLamprey gonadotropin releasing‐hormone (LGnRH)‐III, a hypothalamic neurohormone recently isolated from sea lamprey, was reported to have a selective stimulatory effect on follicle‐stimulating hormone (FSH) release in rats and suggested to be the mammalian FSH‐releasing factor. In this study, we determined the relative luteinizing hormone (LH)‐ and FSH‐releasing potency of LGnRH‐III compared to mammalian gonadotropin‐releasing hormone (LHRH) in normal female rats, ovariectomized (OVX) and oestrogen/progesterone substituted rats and the superfused rat‐pituitary cell system. The specificity of LGnRH‐III for the mammalian LHRH receptor was investigated by blocking the receptor with an LHRH antagonist, MI‐1544. In vitro, LGnRH‐III dose‐dependently stimulated both LH and FSH secretion from rat pituitary cells at 10−7 to 10−5 M concentrations, while LHRH stimulated gonadotropin secretion at a 1000‐fold lower doses (10−10 to 10−8 M). The difference between its LH‐ and FSH‐releasing potency was similar to that of LHRH. LGnRH‐III bound to high affinity binding sites on rat pituitary cells with a Kd of 6.7 nm, Bmax=113±27 fmol/mg protein. In vivo, LGnRH‐III also stimulated both LH and FSH secretion in a dose‐dependent manner and, similar to LHRH, induced a greater rise in the serum LH than the FSH level. In normal cycling rats, it showed 180–650‐fold weaker potency than LHRH in stimulating LH secretion and 70–80‐fold weaker effect in stimulating FSH secretion. In OVX rats, LGnRH‐III demonstrated a similarly weak effect on both gonadotropins. It was found to be 40–210‐fold less potent than LHRH regarding LH release and 50–160‐fold weaker regarding FSH release. LHRH‐receptor antagonist MI‐1544 prevented both the LH‐ and the FSH‐releasing effect of LGnRH‐III both in vitro and in vivo. These results do not support the hypothesis that LGnRH‐III might be the mammalian FSH‐releasing factor but demonstrate that it is a weak agonist for the pituitary LHRH receptor and stimulates both gonadotropins in a dose‐dependent fashion.
Expression of cAMP Response Element Binding Protein‐Binding Protein in the Song Control System and Hypothalamus of Adult European Starlings (Sturnus vulgaris)
Authors: Auger C. J. , Bentley G. E. , Auger A. P. , Ramamurthy M. , Ball G. F. 
Published: March 2003

AbstractIn songbirds, the initiation of song behaviour and the neural substrate of this system are highly influenced by gonadal steroids. Receptors for gonadal steroid hormones, such as androgens and oestrogens, have been localized within select nuclei of the song system. An important step in steroid receptor action is the recruitment of nuclear receptor coactivators. The coactivator, cAMP response element binding protein (CREB)‐binding protein (CBP), has been implicated in both androgen and oestrogen receptor transactivation. Although the role of CBP in transcriptional mechanisms has been widely studied, little is known about CBP expression in the brain. The association between the distribution of CBP and oestrogen receptors in the hippocampus has been related to long‐term memory. However, the distribution of brain CBP has not been related to the expression of gonadal steroid receptors in a system as relevant to reproductive behaviour as the avian song system. Western immunoblotting of European starling (Sturnus vulgaris) brain tissue reveals a band at 265 kDa. Immunohistochemical localization of CBP in starling brain indicates wide, but heterogeneous expression. CBP‐immunoreactive (CBP‐ir) cells define the boundaries of song control nuclei. In HVc (sometimes called the High Vocal Center) and the robust nucleus of the archistriatum (RA), there is a higher density of CBP‐ir cells within the boundaries of these nuclei than in adjacent neostriatum or archistriatum, for HVc and RA, respectively. We also report that the distribution of CBP‐ir cells varies among different nuclei within the song control system. CBP‐ir cells within area X (also a part of the song system) and HVc are densely packed into clusters, whereas cells can be easily discriminated in RA. CBP is also highly expressed in hypothalamic areas, indicating that areas rich in steroid receptors also contain CBP. These data suggest that CBP is important for modulating transcriptional activities in the song system and other sites in the songbird brain that express gonadal steroid receptors.
The Effects of the Phytoestrogen, Coumestrol, on Gonadotropin‐Releasing Hormone (GnRH) mRNA Expression in GT1‐7 GnRH Neurones
Authors: Bowe J. , Li X. F. , Sugden D. , Katzenellenbogen J. A. , Katzenellenbogen B. S. , O'Byrne K. T. 
Published: March 2003

AbstractPhytoestrogens can produce inhibitory effects on gonadotropin secretion in both animals and humans, although little is known about the mechanisms and the role of direct action on oestrogen receptors (ER) in this process. We examined the effect of coumestrol, alone and combined with ER antagonists, on gonadotropin‐releasing hormone (GnRH) mRNA expression in GT1‐7 cells. Coumestrol was found to have an inhibitory effect compared to controls, which was blocked by R,R‐THC, a selective ERβ antagonist. These results suggest that ERβ is involved in the suppression of GnRH mRNA expression by coumestrol.
Recurrent headache in patients with temporomandibular disorders of mainly arthrogenous origin. A short‐ and long‐term evaluation of the treatment effect of occlusal appliance therapy. A randomized controlled trial
Authors: NILNER M. , EKBERG E. , VALLON D. 
Published: March 2003

Introduction:  In patient material recurrent headache has been presented in about 40–70%.Aim:  The aim of this study was to evaluate recurrent headache before and after treatment with a stabilization or control appliance. The effect of treatment should be evaluated both in a short and long time perspective.Materials and methods:  Sixty patients with TMD of mainly arthrogenous origin were selected from patients referred for treatment of TMD. The patients were randomly assigned to a treatment group (T), stabilization appliance, and a control group (C), control appliance. The study was performed as a randomized controlled trial evaluating the treatment effect after 10 weeks, 6 and 12 months. Patients who reported a negative treatment outcome and/or any discomfort associated with the appliances either had their appliances adjusted or received a stabilization appliance creating a new mixed group (M).Results:  In the T and C groups, 77 and 83% respectively, reported headache at least once a week before treatment. At the 10 week follow‐up a statistically significant difference was found regarding less frequent headache within the T‐group but not within the C‐group. Frequent headache was also found statistically significantly less often in the T‐group compared with the C‐group. At the 6 and 12 month follow‐ups the frequency of headache seemed to have diminished within groups.Conclusion:  Treatment with a stabilization appliance seems to have a positive effect on recurrent headache in a short‐ and long‐term perspective in patients with TMD of mainly arthrogenous origin.
Pharmacokinetics of cisapride in the horse
Authors: Steel  , Bolton  , Preechagoon  , Charles  
Published: March 2003

The purpose of this study was to determine the pharmacokinetics and absolute bioavailability of cisapride after intravenous (i.v.) and intragastric (i.g.) administration in healthy, adult horses. Five animals received single doses of 0.1 mg/kg, 0.2 mg/kg and 0.4 mg/kg cisapride by the i.g. route in an open, randomized fashion on different occasions separated by a washout period of at least 48 h. Four of these horses were also given a single i.v. dose of 0.1 mg/kg cisapride. Jugular venous blood was collected periodically up to 24 h after dosing. Plasma cisapride concentrations were measured by high‐performance liquid chromatography. There was considerable inter individual variability in pharmacokinetic parameters. The mean (SD) values for systemic clearance (Cl) and steady‐state volume of distribution (Vss) were 494 (43.6) mL/h/kg and 1471 (578) mL/kg, respectively. Although the rate of cisapride absorption was quite rapid, only about half the i.g. dose was absorbed systemically. The average terminal half‐life (t½) calculated over three i.g. doses was 2.06 h and that for i.v. administration was 2.12 h. The pharmacokinetics of cisapride from 0.1 mg/kg to 0.4 mg/kg were independent of the i.g. dose.