bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct Action of Serotonin on Prolactin, Growth Hormone, Corticotropin and Luteinizing Hormone Release in Cocultures of Anterior and Posterior Pituitary Lobes: Autocrine and/or Paracrine Action of Vasoactive Intestinal Peptide
Authors: Balsa José Antonio , Sánchez-Franco Franco , Pazos Fernando , Lara José Ignacio , Lorenzo María Jesús , Maldonado Gonzalo , Cacicedo Lucinda 
Published: April 2003

There is extensive evidence that serotonin (5-HT) is implicated in the neuroendocrine control regulating the secretion of several anterior pituitary hormones. It has also been reported that the posterior pituitary is necessary for prolactin (PRL) response to 5-HT as well as to suckling, in which 5-HT implication has been demonstrated. As we have previously shown that vasoactive intestinal peptide (VIP) mediates through an autocrine or paracrine action the PRL release induced by insulin-like growth factor I, thyrotropin-releasing hormone (TRH) and dopamine withdrawal, the aim of the present work was to determine whether 5-HT has a direct action on pituitary secretion and to study the possible role of pituitary VIP in this situation. Cells from the anterior pituitary lobe (AP) were cultured either alone or together with cells from the posterior pituitary lobe (PP). As melanotropes from PP express glucocorticoid receptors in vitro, both AP cultures and cocultures of AP/PP cells were incubated in the presence or absence of corticosterone (0.1 µg/ml), thus designing four experimental conditions. Then both AP and mixed cultures were incubated with 5-HT (100 n<i>M</i>) for 20, 45 and 180. The release of PRL, growth hormone (GH), corticotropin (ACTH) and luteinizing hormone (LH) was stimulated by 5-HT, but only in cocultures of AP/PP cells preincubated with corticosterone, whereas follicle-stimulating hormone and thyroid-stimulating hormone release was not modified. As AP cultures did not show any response to 5-HT, both in the presence or absence of corticosterone, and as melanotropes are the main cellular type present in the PP cultures, we studied the response of α-melanocyte-stimulating hormone (αMSH) to 5-HT in PP cells cultured with or without corticosterone. Serotonin did not modify αMSH release either in the absence or the presence of corticosterone. VIP release was also stimulated by 5-HT in the cocultures, and the time response profile was only similar to that of PRL. In order to study whether pituitary VIP is implicated in 5-HT action, cocultures preincubated with corticosterone were incubated in the presence of 5-HT, a VIP-receptor antagonist (VIP-At) or simultaneously with 5-HT plus VIP-At. PRL response to 5-HT was abolished by the simultaneous presence of VIP-At, whereas GH, ACTH and LH response remained unchanged. These data demostrate that: (1) 5-HT stimulates the secretion of PRL, GH, ACTH, LH and VIP acting directly at pituitary level on PP, probably by releasing an unidentified mediator from melanotropes; (2) glucocorticoids make the response of AP cells to 5-HT possible due to the presence of PP cells in the coculture; (3) PRL response to 5-HT is mediated through an autocrine and/or paracrine action of VIP.
Hyporesponsiveness of the Pituitary to CRH during Slow Wave Sleep Is Not Mimicked by Systemic GHRH
Authors: Antonijevic Irina A. , Murck Harald , Frieboes Ralf-Michael , Holsboer Florian , Steiger Axel 
Published: April 2003

During slow wave sleep (SWS) pituitary responsiveness to CRH is reduced. Since GHRH is involved in the promotion of SWS in humans and rats, it was examined whether the blunted CRH-induced ACTH and cortisol release during SWS could be mimicked by systemic GHRH. Young healthy men (n = 7) participated in 4 sleep-endocrine protocols: (A) lights off at 23.00 h, intravenous injection of 50 µg CRH during the first SWS period; (B) lights off at 01.00 h, injection of 100 µg GHRH at 23.00 h, followed by 50 µg CRH at 23.30 h; (C) lights off at 01.00 h, injection of 50 µg CRH at 23.30 h, and (D) lights off at 23.00 h, saline treatment only (= baseline condition). The sleep EEG was recorded during the lights off period and blood samples, collected every 20 min between 22.00 and 07.00 h, were assayed for GH, cortisol and ACTH. There was no significant difference in the sleep-associated GH peak between protocols. Plasma ACTH was significantly higher following CRH administration during wakefulness compared with CRH administration during SWS (protocols B and C vs. A; area under the curve (AUC) 23.00–03.00 h: 9.6 ± 4.8 and 7.3 ± 2.0 vs. 6.1 ± 1.1 ng/ml × min; p < 0.05), while there was no significant difference in plasma ACTH concentration between the baseline condition and protocol A (CRH administration during SWS). Similarly, cortisol was significantly enhanced compared with baseline following CRH during wakefulness only. CRH induced an increase in EEG activity in the sigma frequency range, both when it was administered during wakefulness and SWS, while this effect was reduced by pre-treatment with GHRH. In summary, our data suggest that (1) the blunted CRH-induced release of ACTH and cortisol during SWS is not mimicked by systemic GHRH administration, and (2) CRH enhances sigma EEG activity possibly via modulation of afferent pathways from the median eminence to the thalamus and this effect is reduced by pre-treatment with GHRH.
Effect of Selective Blockade of Catecholaminergic Alpha and Beta Receptors on Histamine-Induced Release of Corticotropin and Prolactin
Authors: Willems Edwin , Knigge Ulrich , Jørgensen Henrik , Kjær Andreas , Warberg Jørgen 
Published: April 2003

We investigated the role of adrenergic receptors in histamine (HA)-induced release of corticotropin (ACTH) and prolactin (PRL) in conscious male rats. Specific α- or β-receptor antagonists were administered intracerebroventricularly in doses of 1 mmol at time –20 min, and HA (270 nmol), the H<sub>1</sub> receptor agonist 2-thiazolylethylamine (2-TEA; 2,180 nmol) or the H<sub>2</sub> receptor agonist 4-methylHA (4-MeHA; 790 nmol) were administered intracerebroventricularly at –15 min. The animals were decapitated at 0 min, and plasma was analyzed for ACTH and PRL. Administration of HA and the histaminergic agonists stimulated ACTH secretion equally, while only HA and the H<sub>2</sub> receptor agonist stimulated PRL secretion. Pretreatment with the adrenergic receptor antagonists had no effect on the ACTH response to the histaminergic compounds. In contrast, the PRL response to HA or 4-MeHA was inhibited or prevented by the α-receptor antagonists phenoxybenzamine and phentolamine, the α<sub>1</sub>-receptor antagonist prazocin, the β-receptor antagonist propranolol and the β<sub>1</sub>-receptor antagonist atenolol, whereas the α<sub>2</sub>-receptor antagonist yohimbine or the β<sub>2</sub>-receptor antagonist ICI-118-551 had no effect. The study indicates that histaminergic neurons interact with the catecholaminergic neuronal system in regulation of PRL secretion, and that this interaction is dependent upon activation of α<sub>1</sub>- and β<sub>1</sub>-receptors. In contrast, histaminergic neurons stimulate ACTH secretion independently of adrenergic receptor activation.
Role of Glucocorticoids in the Response of the Hypothalamo-Corticotrope, Immune and Adipose Systems to Repeated Endotoxin Administration
Authors: Chautard Thierry , Spinedi Eduardo , Voirol Marie-Jeanne , Pralong François P. , Gaillard Rolf C. 
Published: April 2003

The present study was designed to determine whether the glucocorticoid inhibitory feedback mechanism plays a role in the well-known tolerance of the neuroendocrine-immune axis response to repeated endotoxemia. Adult male rats underwent adrenalectomy (ADX) and were implanted with a subcutaneous corticosterone (compound B, CB, 75 mg) pellet, or sham operated and implanted with a placebo pellet. On the morning of day 8 after surgery (experimental day, D1), all rats received an intravenous injection of lipopolysaccharide (LPS) (25 µg/kg body weight) which was repeated daily until D5. Blood was drawn via intravenous indwelling catheters before (sample time zero) as well as 1, 2, 3 and 4 h after LPS treatment on D1, 3 and 5 for measurements of corticotropin (ACTH), CB, tumor necrosis factor-α (TNF-α) and leptin. In sham animals, tolerance to repeated LPS administration was complete by D5 for the corticotrope axis and the immune response. In addition, LPS was found to stimulate leptin secretion on day 1 in intact rats, an effect that also disappeared thereafter. ADX + CB rats showed only a partial tolerance of the corticotrope axis on D5, whereas tolerance of the immune response was similar to that found in sham animals. Interestingly, the acute stimulation of leptin secretion by LPS in ADX + CB rats was qualitatively similar to that of intact controls on D1, but plasma leptin levels were significantly reduced on D3 and 5 compared to controls. Our results demonstrate that the adrenal response tolerance of the hypothalamo-pituitary-adrenal axis to repeated endotoxemia. In addition, our finding that TNF-α secretion follows the same pattern in sham-operated and in adrenalectomized animals suggests that unlike the corticotrope axis, tolerance of the immune response does not depend upon stimulated CB levels. The decrease in circulating levels of leptin following ADX is consistent with the stimulatory effects of glucocorticoids on leptin secretion. However, our finding of an acute stimulation of leptin secretion by LPS in ADX + CB animals demonstrates that this effect of endotoxemia is at least partially glucocorticoid independent.
PC18, a Specific Aminopeptidase N Inhibitor, Induces Vasopressin Release by Increasing the Half-Life of Brain Angiotensin III
Authors: Réaux Annabelle , de Mota Nadia , Zini Sylvie , Cadel Sandrine , Fournié-Zaluski Marie-Claude , Roques Bernard P. , Corvol Pierre , Llorens-Cortès Catherine 
Published: April 2003

Angiotensin III (AngIII), which is metabolized in vivo by aminopeptidase N (APN), was previously shown to be one of the main effector peptides of the brain renin-angiotensin system (RAS) in the control of vasopressin release. Recently, a potent APN inhibitor, PC18 (2-amino-4-methylsulfonyl butane thiol, methionine thiol), has been developed. In this study, we first checked the in vitro selectivity of PC18 towards APN, aminopeptidase A (APA) and aminopeptidase B (APB), three zinc metalloproteases with significant identity between their amino acid sequences. The K<sub>i</sub> values of this compound on APN were found to be in the nanomolar range (K<sub>i</sub> = 8.0 ± 1.7 n<i>M</i>) but it was 2,150 and 125 times less active on APA and APB, respectively. Secondly, we evaluated in vivo the effect of brain APN inhibition with PC18 on the inactivation of brain AngIII and on vasopressin secretion in mice. For this purpose, mice received [<sup>3</sup>H]AngII intracerebroventricularly in the presence or absence of the APN inhibitor PC18 (30 µg). At different times after the injection, [<sup>3</sup>H]AngIII levels were evaluated from hypothalamus homogenates after separation by cation-exchange chromatography. PC18 induced an accumulation of [<sup>3</sup>H]AngIII, increasing its half-life 3.9 times as compared with control values. In addition, the effect of PC18 on vasopressin release was studied in mice. PC18 (10–100 µg) was injected intracerebroventricularly, and plasma vasopressin levels were estimated by radioimmunoassay. PC18 increased vasopressin levels in a dose-dependent manner. The maximal increase in vasopressin release (+220%) is observed for a dose of PC18 of 100 µg and was inhibited 75% by the coadministration of the AngII receptor antagonist (Sar<sup>1</sup>–Ala<sup>8</sup>)-AngII (0.5 µg). These results indicate that in vivo, in the mouse brain, APN inhibition by PC18 increases the half-life of endogenous AngIII, resulting in an enhanced vasopressin release.
Cloning of Proopiomelanocortin from the Brain of the African Lungfish, <i>Protopterus annectens</i>, and the Brain of the Western Spadefoot Toad, <i>Spea multiplicatus</i>
Authors: Lee Jenny , Lecaude Stephanie , Danielson Phillip , Sollars Cristina , Alrubaian Jasem , Propper Catherine R. , Lihrmann Isabelle , Vaudry Hubert , Dores Robert M. 
Published: April 2003

A degenerate primer, specific for the opioid core sequence YGGFM, was used to clone and sequence proopiomelanocortin (POMC) cDNAs from the brain of the African lungfish, <i>Protopterus annectens</i>, and from the brain of the western spadefoot toad, <i>Spea multiplicatus</i>. In addition, the opioid-specific primer was used to clone and sequence a 3′RACE product corresponding to a portion of the open reading frame of <i>S. multiplicatus</i> proenkephalin. For both species, cDNA was made from a single brain and a degenerate opioid-specific primer provided a reliable probe for detecting opioid-related cDNAs. The African lungfish POMC cDNA was 1,168 nucleotides in length, and contained regions that are similar to tetrapod POMCs and fish POMCs. The African lungfish POMC encodes a tetrapod-like γ-MSH sequence that is flanked by sets of paired basic amino acid proteolytic cleavage sites. The γ-MSH region in ray-finned fish POMCs either has degenerate cleavage sites or is totally absent in some species. However, the African lungfish γ-MSH sequence does contain a deletion which has not been observed in tetrapod γ-MSH sequences. The β-endorphin region of lungfish POMC has the di-amino acid sequence tryptophan-aspartic acid in the N-terminal region and an additional glutamic acid residue in the C-terminal region of β-endorphin – features found in fish β-endorphin, but not tetrapod β-endorphins. The western spadefoot toad POMC was 1,186 nucleotides in length, and exhibited an organizational scheme typical for tetrapod POMCs. However, the toad POMC did lack a paired basic amino acid proteolytic cleavage site N-terminal to the β-MSH sequence. Thus, like rat POMC, it is doubtful that β-MSH is an end product in either the toad brain or intermediate pituitary. At the amino acid level, the toad POMC had 76% sequence identity with <i>Xenopus laevis</i> POMC and 68% sequence identity with <i>Rana ribidunda</i> POMC. The use of these POMC sequences to assess phylogenetic relationships within anuran amphibians will be discussed. With respect to the fragment of <i>S. multiplicatus</i> proenkephalin cDNA, two metenkephalin sequences and the metenkephalin-RF sequence were found encoded in this fragment. As seen for <i>X. laevis</i> and <i>R. ridibunda</i> proenkephalin, a leuenkephalin sequence was not detected in the C-terminal region of the <i>S. multiplicatus</i> proenkephalin. The absence of a leuenkephalin sequence may be a common feature of anuran amphibian proenkephalins.
Differential Effects of Pregnancy on Mineralocorticoid and Glucocorticoid Receptor Availability and Immunoreactivity in Cortisol Feedback Sites
Authors: Roesch Darren M. , Keller-Wood Maureen 
Published: April 2003

The suppression of plasma adrenocorticotropic hormone by very low levels of cortisol is reduced in pregnant adrenalectomized ewes, suggesting that pregnancy reduces the efficacy of the high-affinity corticosteroid receptor. This study was designed to determine the effects of pregnancy on the availability, immunoreactivity, and affinity of both corticosteroid receptors: the high-affinity mineralocorticoid receptor (MR) and the lower-affinity glucocorticoid receptor (GR). Availability was measured in the hypothalamus, pituitary, hippocampus and kidney using a saturation point radioligand binding assay. GR availability was significantly decreased in hippocampal cytosols obtained from pregnant ewes, but did not significantly change in other tissues. This finding is consistent with increased GR activation due to elevated circulating concentrations of cortisol. MR availability significantly increased from undetectable levels in hippocampal cytosols obtained from nonpregnant ewes to 2.8 ± 1.6 fmol/mg protein in pregnant ewes, suggesting a reduced MR activation in the hippocampus during pregnancy. MR availability tended to be greater in other tissues during pregnancy, but these differences were not significant. The amount of immunoreactive MR (<i>i</i>MR) and GR (<i>i</i>GR) protein was estimated by quantifying Western blots. <i>i</i>GR significantly increased in the pituitary, but did not significantly change in other tissues. In contrast, <i>i</i>MR was significantly increased during pregnancy in all tissues assayed, suggesting that an increased cytosolic MR protein amount contributes to the observed increase in MR availability. Since studies suggest that progesterone is a potent anticorticosteroid, we tested for evidence of endogenous inhibition of binding to MR and/or GR during pregnancy by determining MR and GR affinity in pituitary cytosols obtained from nonpregnant and pregnant ewes. Although there was a tendency towards a decreased affinity of the MR in pregnant ewes, there was no significant change in the K<sub>D</sub> of the pituitary MR or GR during pregnancy. We hypothesize that an alteration in activation and/or autoregulation of the MR during pregnancy, particularly in the hippocampus, may contribute to the observed changes in receptor availability and immunoreactivity and increase basal plasma cortisol levels during pregnancy.
Brain Potentials and Attention after Acute and Subchronic Intranasal Administration of ACTH 4–10 and Desacetyl-α-MSH in Humans
Authors: Smolnik Rüdiger , Mölle Matthias , Fehm Horst Lorenz , Born Jan 
Published: April 2003

Neuropeptides related to adrenocorticotropin (ACTH) are potent regulators of neurobehavioral functions. In humans, ACTH and its behaviorally active fragment ACTH 4–10 have been consistently found to diminish event-related brain potential (ERP) signs of focussing attention. This study aimed at (1) evaluating effects of ACTH 4–10 on ERP indicators of attention in healthy controls after intranasal administration of the peptide. This route of administration has been proposed to provide a more direct access to the brain than the intravenous administration of the peptide, (2) comparing acute effects and effects of a subchronic treatment with ACTH 4–10, and (3) comparing effects of ACTH 4–10 with those of desacetyl-α-MSH (corresponding to ACTH 1–13 amide) which like ACTH 4–10 binds to subgroups of the melanocortin receptor family. Double-blind placebo-controlled experiments were completed in 54 healthy young subjects. ERPs were recorded while the subject performed an auditory selective attention task. Moreover, a modified Stroop interference test including motivational (food, sex) and nonmotivational words was performed. Acute intranasal administration of ACTH 4–10 (1 mg) reduced the processing negativity (PN) of the ERP over frontal and central cortical areas (p < 0.05) indicating diminished focussing of attention. Moreover, on this condition subjects were more prone to interference on the Stroop task especially with motivational words (p < 0.05). Subchronic administration of ACTH 4–10 (1 mg/day over 6 weeks) did not affect PN and Stroop performance. Acute intranasal administration of desacetyl-α-MSH at equimolar doses (1.68 mg) also remained ineffective. However, some measures of Stroop performance appeared to improve after subchronic desacetyl-α-MSH treatment. Results confirm an acute decrease in focussing of attention after ACTH 4–10. These effects of intranasal administration are likely to reflect a direct action of the peptide on respective brain functions. Moreover, they were specific to ACTH 4–10 and were not obtained after equimolar doses of desacetyl-α-MSH, thus excluding a mediation via the known melanocortin receptors.
Activation of Arcuate Nucleus Neurons by Systemic Administration of Leptin and Growth Hormone-Releasing Peptide-6 in Normal and Fasted Rats
Authors: Luckman Simon M. , Rosenzweig Ivana , Dickson Suzanne L. 
Published: April 2003

Both leptin and growth hormone secretagogues are believed to have stimulatory effects on the hypothalamic growth hormone pulse generator, though whether these are achieved through the same pathway is unknown. Systemic administration of a normally maximal effective dose of the growth hormone secretagogue GHRP-6 to male rats causes the induction of c-Fos protein in the ventromedial aspect of the hypothalamic arcuate nucleus. The effect of the same dose of GHRP-6 is, however, much greater in animals that have been fasted for 48 h, suggesting that in the food-replete rat, arcuate neurons either show reduced sensitivity to endogenous growth hormone secretagogues or they are under the tonic inhibitory influences of other factors. The major populations of arcuate neurons activated by GHRP-6 have been shown to contain neuropeptide Y or growth hormone-releasing factor, while leptin is thought to be inhibitory to neuropeptide Y neurons. Leptin did not alter the response of the rats to GHRP-6. However, it was able by itself to induce c-Fos protein immunoreactivity in the ventral, including the ventrolateral, arcuate nucleus of fasted rats. This is a clear demonstration of the acute activation of arcuate neurons in the rat following systemic leptin injection and suggests that GHRP-6 and leptin act on the growth hormone axis via different pathways.
Evidence that Neuronal Nitric Oxide Synthase but Not Heme Oxygenase Increases in the Hypothalamus on Proestrus Afternoon
Authors: Lamar Charisee A. , Bhat Ganapathy K. , Mahesh Virendra B. , Brann Darrell W. 
Published: April 2003

Nitric oxide (NO) has been implicated in the control of the proestrus luteinizing hormone (LH) surge in the rat but to date no studies have attempted to measure neuronal nitric oxide synthase (nNOS) or NO production on proestrus in the hypothalamus in order to determine if endogenous NO is increased on proestrus afternoon to activate gonadotropin-releasing hormone (GnRH) neurons. To address this deficit in our knowledge, we measured nNOS mRNA and protein levels as well as NOS activity levels in rat preoptic area (POA) and medial basal hypothalamus (MBH) fragments at 12.00, 14.00, 16.00, and 18.00 h of proestrus. Serum LH levels were also assessed to determine whether NOS changes correlate to the LH surge. To determine the specificity of observed changes we also measured mRNA levels for the enzyme heme oxygenase-2, which is responsible for production of another putative gaseous transmitter, carbon monoxide. In all studies a metestrus 12.00 h control group was included since steroid and LH levels would be basal at this time as compared to proestrus. The results revealed that nNOS mRNA and protein levels, as well as NOS activity did not change significantly in the MBH on proestrus. In contrast, nNOS mRNA levels were significantly elevated in the POA at proestrus 12.00 and 14.00 h, as compared to metestrus 12.00 h. Likewise, at the protein and activity level, nNOS protein levels in the POA were significantly elevated on proestrus at 14.00 and 16.00 h, with NOS activity significantly increased at 16.00 h on proestrus. The elevation of nNOS protein and activity levels in the POA occurred at the time of initiation of the LH surge. The elevation of nNOS was specific as mRNA levels for the CO-synthetic enzyme heme oxygenase-2 did not change significantly on proestrus in the POA or MBH. As a whole, the current studies provide new evidence that nNOS is elevated in the POA on proestrus, and thus could play a role in the activation of GnRH neurons to produce the preovulatory LH surge.