bluuebunny/crossref_metadata_2025_split huggingface dataset:
Partial Characterization of Circulating Inhibin-B and Pro-αC During Development in the Male Rhesus Monkey1
Authors: Winters Stephen J. , Plant Tony M. 
Published: January 2014

AbstractGel filtration chromatography and ELISAs for inhibin-B and pro-αC were used to examine the circulating forms of inhibin in the neonatal (age 2–6 weeks), juvenile (age 1–2 yr), and adult male rhesus monkey. In all samples, isoforms of inhibin-B of 26–36K and 150K were found. Both forms were significantly greater in the adult. Theα -subunit assay detected major peaks at 45–60 and 29–31K, and a minor peak of greater than 100K. As for inhibin-B, the major forms of inhibin pro-αC were highest in adulthood. Inhibin-B and pro-αC were measurable in peripheral plasma at age 1 week, increased with the neonatal rise in plasma FSH, and then decreased but remained detectable through age 1 yr. Values in adult males were higher than at any time during the first year of life. Finally, mean values of plasma inhibin-B and pro-αC in five monkeys, based on multiple blood samples drawn between age 1 week and 1 yr, were rank ordered and were found to be highly positively correlated (r = 0.96), suggesting that inhibin levels in the first year of life may be a marker of Sertoli cell number, and may predict the spermatogenic capacity of the testis in adulthood.
Endotoxin Stimulates Nitric Oxide Production in the Paraventricular Nucleus of the Hypothalamus through Nitric Oxide Synthase I: Correlation with Hypothalamic-Pituitary-Adrenal Axis Activation1
Authors: Uribe Rosa Maria , Lee Soon , Rivier Catherine 
Published: January 2014

AbstractNitric oxide (NO) is an unstable gas that is produced in brain tissues involved in the control of the activity of the hypothalamus-pituitary-adrenal (HPA) axis. Transcripts for constitutive neuronal NO synthase (NOS I), one of the enzymes responsible for NO formation in the brain, is up-regulated by systemic endotoxin[ lipopolysaccharide (LPS)] injection. However, this change is delayed compared with LPS induced-ACTH release, which makes it difficult to determine whether it is functionally important for the hormonal response. To obtain a more resolutive time course of the NO response, we first measured NO in microdialysates of the paraventricular (PVN) nucleus of the hypothalamus. The iv injection of 100 μg/kg LPS induced a rapid and short-lived increase in concentrations of this gas, which corresponded to the initiation of the ACTH response. LPS-induced Ca2+-dependent NOS activity in the PVN as well as the number of PVN cells expressing citrulline (a compound produced stoichiometrically with NO) also increased significantly over a time course that corresponded to ACTH and corticosterone release. Finally, blockade of NO production with the arginine derivative Nω-nitro-l-arginine-methylester (L-NAME; 50 mg/kg, sc), which attenuated the ACTH response to LPS, virtually abolished basal NOS activity in the PVN, as well as anterior and neurointermediate lobes of the pituitary, and prevented the appearance of citrulline in the PVN of rats injected with LPS.Collectively, these results show that LPS-induced activation of the HPA axis correlates with the activation of the PVN NOergic system, and supports a stimulatory role for NO in the modulation of the HPA axis in response to immune challenges.
Central Administration of Leptin to Ovariectomized Ewes Inhibits Food Intake without Affecting the Secretion of Hormones from the Pituitary Gland: Evidence for a Dissociation of Effects on Appetite and Neuroendocrine Function*
Authors: Henry Belinda A. , Goding James W. , Alexander Warren S. , Tilbrook Alan J. , Canny Benedict J. , Dunshea Frank , Rao Alexandra , Mansell Ashley , Clarke Iain J. 
Published: January 2014

Abstract
We have studied the effect of leptin on food intake and neuroendocrine function in ovariectomized ewes. Groups (n = 5) received intracerebroventricular infusions of either vehicle or leptin (20μ g/h) for 3 days and were blood sampled over 6 h on days −1, 2, and for 3 h on day 3 relative to the onset of the infusion. The animals were then killed to measure hypothalamic neuropeptide Y expression by in situ hybridization. Plasma samples were assayed for metabolic parameters and pituitary hormones. Food intake was reduced by leptin, but did not change in controls. Leptin treatment elevated plasma lactate and nonesterified fatty acids, but did not affect glucose or insulin levels, indicating a state of negative energy balance that was met by the mobilization of body stores. Pulse analysis showed that the secretion of LH and GH was not affected by leptin treatment, nor were the mean plasma concentrations of FSH, PRL, or cortisol. Expression of messenger RNA for neuropeptide Y in the arcuate nucleus was reduced by the infusion of leptin, primarily due to reduced expression per cell rather than a reduction in the number of cells observed. Thus, the action of leptin to inhibit food intake is dissociated from neuroendocrine function. These results suggest that the metabolic effects of leptin are mediated via neuronal systems that possess leptin receptors rather than via endocrine effects.
Prostaglandin E2 Cooperates with TRANCE in Osteoclast Induction from Hemopoietic Precursors: Synergistic Activation of Differentiation, Cell Spreading, and Fusion
Authors: Wani Mohan R. , Fuller Karen , Kim Nack Sung , Choi Yongwon , Chambers Tim 
Published: January 2014

AbstractIt was recently found that osteoblastic cells express TRANCE (tumor necrosis factor-related activation-induced cytokine), a newly identified member of the tumor necrosis factor superfamily, and that expression was increased by calciotropic hormones. Furthermore, soluble recombinant TRANCE induces osteoclast formation and resorption in stroma-free populations of hemopoietic precursor cells. However, overexpression of the decoy receptor osteoprotegerin in vivo shows that there are substantial differences in the sensitivity of different sites to resorption-inhibition, suggesting that either alternative ligands exist or the sensitivity of osteoclasts to TRANCE can be modified by cofactors. We therefore tested the possibility that cofactors might enhance osteoclast formation by TRANCE. We found that the number of tartrate-resistant acid phosphatase-positive and calcitonin receptor-positive cells was increased by a factor of 10 by the presence of PGE2 in the absence of stromal cells. Moreover, although the tartrate-resistant acid phosphatase-positive cells that formed in TRANCE alone were typically mononuclear and poorly spread, the addition of PGE2 induced the formation of large, well spread multinuclear cells. There was an increase in bone resorption that corresponded with the increase in osteoclast number. PGE2 did not synergize with TRANCE for resorption-stimulation in mature cells. 8-Bromo-cAMP showed a similar syngergistic effect on osteoclastic differentiation. Thus, PGE2 appears to stimulate bone resorption through a direct effect on hemopoietic precursors, primarily through a synergistic effect on the ability of TRANCE to induce osteoclastic differentiation.
Evidence for Stanniocalcin Gene Expression in Mammalian Bone*
Authors: Yoshiko Yuji , Son Aoi , Maeda Shuji , Igarashi Akira , Takano Shoichi , Hu Jianguo , Maeda Norihiko 
Published: January 2014

AbstractStanniocalcin (STC) acts as a regulator of calcium and phosphate homeostasis in an endocrine manner in bony fish. Recently, complementary DNAs encoding human and mouse STC have been characterized, and the messenger RNA (mRNA) expression was identified in various tissues, such as kidney, small intestine, prostate, thyroid, and ovary. Because previous studies concerning the effects of fish STC on mammalian bone have been discussed, there is a good possibility that mammalian STC is a local factor in bone. Here, we demonstrated STC mRNA expression in neonatal mouse calvaria, the primary cultured mouse osteoblast-rich fractions, and human and mouse osteoblastic cell lines. We also mapped the cellular distribution of the STC mRNA in femur and calvaria in developing mice. Several transcripts with a major 4-kb band were detected in all samples. The cellular distribution of the mRNA expression corresponded closely to osteoblasts in both femur and calvaria. Significant labeling of the STC mRNA was also identified in chondrocytes but not in osteoclasts and other bone marrow elements. These results are the first evidence that hormone may be actually expressed in osteoblasts and chondrocytes, and they strongly implicate the involvement of local STC in both endochondral and membrane bone as an autocrine/paracrine factor.
Differential Posttranscriptional Regulation of Androgen Receptor Gene Expression by Androgen in Prostate and Breast Cancer Cells*
Authors: Yeap Bu B. , Krueger Romano G. , Leedman Peter J. 
Published: January 2014

AbstractAndrogens, via the androgen receptor (AR), modulate the growth and proliferation of prostate and breast cancer cells. However, the molecular mechanisms underlying the regulation of AR gene expression by androgen in these cells remain to be fully elucidated. To explore differences in AR gene expression between these hormone-responsive tumor cell types, we studied androgen-responsive LNCaP prostate cancer and AR positive MDA453 breast cancer cells. Dihydrotestosterone (DHT) 10 nm increased LNCaP cell proliferation and the proportion of LNCaP cells in S-phase of the cell cycle but inhibited MDA453 cell proliferation and reduced the proportion of MDA453 cells in S-phase of cell cycle. In both these cell lines, DHT decreased total AR messenger RNA (mRNA) but increased AR protein. In LNCaP cells, DHT down-regulated AR mRNA transcription but stabilized AR mRNA. In contrast, in MDA453 cells, DHT had no effect on AR mRNA transcription but destabilized AR mRNA. In summary, transcriptional down-regulation induced by androgens in LNCaP cells results in down-regulation of steady-state AR mRNA despite an androgen-induced increase in AR mRNA stability. However, in MDA453 cells, posttranscriptional destabilization of AR mRNA appears to be the predominant mechanism resulting in down-regulation of AR mRNA by androgen. These results demonstrate cell-specific and divergent regulation of AR mRNA turnover by androgen and identify a novel pathway of androgen-induced posttranscriptional destabilization and down-regulation of AR mRNA in human breast cancer cells. Furthermore, these data establish an important role for posttranscriptional pathways in the regulation of AR gene expression by androgen in human prostate and breast cancer cells.
Histaminergic and Catecholaminergic Interactions in the Central Regulation of Vasopressin and Oxytocin Secretion*
Authors: Knigge Ulrich , Willems Edwin , Kjær Andreas , Jørgensen Henrik , Warberg Jørgen 
Published: January 2014

Abstract
Activation of histaminergic and noradrenergic/adrenergic neurons in the brain stimulates the release of the neurohypophysial hormones arginine vasopressin (AVP) and oxytocin (OT) and are involved the mediation of the hormone responses to physiological stimuli such as dehydration and suckling. We therefore investigated whether the two neuronal systems interact in their regulation of AVP and OT secretion in conscious male rats. When administered intracerebroventricularly (icv), histamine (HA) as well as the H1 receptor agonist 2-thiazolylethylamine or the H2 receptor agonist 4-methylHA stimulated AVP and OT secretion. Prior icv infusion of antagonists specific to α or β adrenergic receptors or their subtypes did not significantly affect the hormone response to HA or the histaminergic agonists. Infused icv norepinephrine (NE) or epinephrine (E) increased AVP and OT secretion. Prior icv infusion of the H1 receptor antagonist mepyramine or the H2 receptor antagonist cimetidine significantly inhibited the AVP and OT responses to NE and the AVP response to E, whereas only cimetidine inhibited the OT response to E significantly. Systemic pretreatment with imetit, which by activation of presynaptic H3 receptors inhibits neuronal synthesis and release of HA, decreased the AVP and OT responses to NE and E significantly. In the doses used, HA and E had no significant effect on mean arterial blood pressure. NE increased mean arterial blood pressure 10% at 1 and 2.5 min, whereafter the blood pressure returned to basal level within 10 min. The results indicate that noradrenergic and adrenergic neurons stimulate AVP and OT secretion via an involvement of histaminergic neurons, which may occur at magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus. The stimulatory effect of the amines on neurohypophysial hormone secretion seems to be independent of a central action on blood pressure. In contrast, a functionally intact noradrenergic and adrenergic neuronal system seems not to be a prerequisite for a HA-induced release of AVP and OT. The present findings further substantiate the role of histaminergic neurons in the central regulation of neurohypophysial hormone secretion.
Parathyroid Hormone-Related Peptide Is a Potent Tumor Angiogenic Factor
Authors: Akino Kozo , Ohtsuru Akira , Kanda Kazuaki , Yasuda Akiko , Yamamoto Toshinori , Akino Yuki , Naito Shinji , Kurokawa Mamoru , Iwahori Nobuharu , Yamashita Shunichi 
Published: January 2014

Abstract
Rat pituitary malignant tumor cells; mGH3, show hypervascularization in in vivo xenografts and overexpress parathyroid hormone-related peptide (PTHrP) compared to original GH3 cells. To elucidate whether PTHrP is involved in tumor-derived angiogenesis, we examined the effect of PTHrP on vascular endothelial cells both in vitro and in vivo. Results of in vivodiffusion chamber assay showed a clear hypervascularization on the outer surface of diffusion chambers containing mGH3 tumor cell implants but not in those containing GH3 cells. Co-incubation with antisense PTHrP oligonucleotide (10 μM), but not sense or mismatched PTHrP oligonucleotide, suppressed hypervascularization in diffusion chambers. To further examine the role of PTHrP on endothelial cell function, PTHrP(1–34) was added at various concentrations to cultured bovine endothelial cells (BAECs) harvested from the aorta. PTHrP(1–34) did not alter the proliferation or migration of endothelial cells, but rather dose-dependently increased capillary formation by endothelial cells on the collagen gel matrix. Furthermore, 0.1 mM of 8-bromo-cAMP caused a similar increase in tube formation, which was dose-dependently inhibited by H89, a protein kinase A inhibitor. Our results indicate for the first time that PTHrP is a potential paracrine factor acting via the PKA pathway to enhance angiogenesis through capillary tube formation by endothelial cells in malignant pituitary tumors.
The Acute and Chronic Stimulatory Effects of Endothelin-1 on Glucose Transport Are Mediated by Distinct Pathways in 3T3-L1 Adipocytes**This work was supported by NIH Grant DK-33651.
Authors: Ishibashi Ken-ichi , Imamura Takeshi , Sharma Prem M. , Ugi Satoshi , Olefsky Jerrold M. 
Published: January 2014

AbstractWe have recently shown that pretreatment with endothelin-1 (ET-1) for 20 min stimulates GLUT4 translocation in a PI3-kinase-dependent manner in 3T3-L1 adipocytes (Imamura, T. et al., J Biol Chem 274:33691–33695). This study presents another pathway by which ET-1 potentiates glucose transport in 3T3-L1 adipocytes. ET-1 treatment (10 nm) leads to approximately 2.5-fold stimulation of 2-deoxyglucose (2-DOG) uptake within 20 min, reaching a maximal effect of ∼4-fold at ∼6 h, and recovering almost to basal levels after 24 h. Insulin treatment (3 ng/ml) results in an approximately 5-fold increase in 2-DOG uptake at 1 h, and recovering to basal levels after 24 h. The ETA receptor antagonist, BQ 610, inhibited ET-1 induced glucose uptake both at 20 min and 6 h, whereas the ETB receptor antagonist, BQ 788, was without effect. Interestingly, ET-1 stimulated 2-DOG uptake at 6 h, not at 20 min, was almost completely blocked by the protein-synthesis inhibitor, cycloheximide and the RNA-synthesis inhibitor, actinomycin D, suggesting that the short-term (20 min) and long-term (6 h) effects of ET-1 involve distinct mechanisms. GLUT4 translocation assay showed that 20 min, but not 6 h, exposure to ET-1 led to GLUT4 translocation to the plasma membrane. In contrast, 6 h, but not 20 min, exposure to ET-1 increased expression of the GLUT1 protein, without affecting expression of GLUT4 protein. ET-1 induced 2-DOG uptake and GLUT1 expression at 6 h were completely inhibited by the MEK inhibitor, PD 98059, and partially inhibited by the PI3-kinase inhibitor, LY 294002, and the Gαi inhibitor, pertussis toxin. The PLC inhibitor, U 73122, was without effect. These findings suggest that ET-1 induced GLUT1 protein expression is primarily mediated via MAPK, and partially via PI3K in 3T3-L1 adipocytes.
Molecular Cloning and Expression of a Functionally Different Alternative Splice Variant of Prointerleukin-1α from the Rat Testis*
Authors: Sultana Taranum , Svechnikov Konstantin , Weber Günther , Söder Olle 
Published: January 2014

AbstractWe report here the characterization of an alternative splice variant of prointerleukin-1α (proIL-1α), constitutively expressed by the normal adult rat testis. In addition to the classical 32K proIL-1α (32proIL-1α) messenger RNA, the testis produced a shorter variant encoding a putative protein of 24K (24proIL-1α). In situ hybridization demonstrated constitutive expression of the splice transcript in the seminiferous tubules. This alternative complementary DNA lacked the fifth exon, harboring the calpain cleavage site essential for generation of mature 17K IL-1α. This was verified by calpain treatment, producing the expected cleavage products of recombinant 32proIL-1α, but not of 24proIL-1α. Similarly, expression in COS-7 cells demonstrated processing of 32proIL-1α to the mature 17K form and secretion, whereas 24proIL-1α remained unprocessed. Both 32proIL-1α and 24proIL-1α showed a dose-dependent stimulatory effect in a thymocyte proliferation assay, although at lower potency than mature 17K IL-1α. In contrast, when tested on hCG-stimulated Leydig cells in vitro, a dose-dependent inhibition of testosterone production was obtained with mature 17K IL-1α and at a lower potency with 32proIL-1α, whereas 24proIL-1α was inactive. In conclusion, the three IL-1 bioactive proteins described here contribute to IL-1 protein heterogeneity and may serve as constitutive paracrine mediators in the testis.
Neuroendocrine Aging in the Female Rat: The Changing Relationship of Hypothalamic Gonadotropin-Releasing Hormone Neurons and N-Methyl-d-Aspartate Receptors**Preliminary versions of this work were presented at the 28th and 29th Annual Meetings of the Society for Neuroscience (Abstracts 110.11 and 777.10). This work was supported by the Brookdale Foundation (to A.C.G.), NIH Grant 1-PO1-AG16765–01 (to A.C.G. and J.H.M.).
Authors: Gore Andrea C. , Yeung Glendy , Morrison John H. , Oung Twethida 
Published: January 2014

Abstract
The reproductive axis undergoes alterations during aging, resulting in acyclicity and the loss of reproductive function. In the hypothalamus, changes intrinsic to GnRH neurons may play a critical role in this process, as may changes in inputs to GnRH neurons from neurotransmitters such as glutamate. We investigated the effects of age and reproductive status on neuroendocrine glutamatergic NMDA receptors (NRs), their regulation of GnRH neurons, and their expression on GnRH neurons, in female rats. First, we quantified NR subunit messenger RNAs (mRNAs) in preoptic area-anterior hypothalamus (POA-AH) and medial basal hypothalamus (MBH), the sites of GnRH perikarya and neuroterminals, respectively. In POA-AH, NR1 mRNA levels varied little with age or reproductive status. NR2a and NR2b mRNA levels decreased significantly between cycling and acyclic rats. In MBH, NR mRNAs all increased with aging, particularly in acyclic animals. Second, we tested the effects of N-methyl-d,l-aspartate (NMA) on GnRH mRNA levels in POA-AH of aging rats. NMA elevated GnRH mRNA levels in young rats, but decreased them in middle-aged rats. Third, we quantified expression of the NR1 subunit on GnRH perikarya in aging rats using double label immunocytochemistry. NR1 expression on GnRH cell bodies varied with age and reproductive status, with 30%, 19%, and 46% of GnRH somata double labeled with NR1 in young proestrous, middle-aged proestrous, and middle-aged persistent estrous rats, respectively. Thus, 1) the expression of hypothalamic NR subunit mRNAs correlates with reproductive status; 2) changes in NR subunit mRNA levels, if reflected by changes in protein levels, may result in alterations in the stoichiometry of the NR during aging, with possible physiological consequences; 3) the effects of NR activation on GnRH mRNA switches from stimulatory to inhibitory during reproductive aging; and 4) expression of the NR1 subunit on GnRH perikarya changes with reproductive status. These molecular, physiological, and cellular neuroendocrine changes are proposed to be involved in the transition to acyclicity in aging female rats.
p38 Mitogen-Activated Protein Kinase Mediates Tumor Necrosis Factor-α-Induced Apoptosis in Rat Fetal Brown Adipocytes*
Authors: Valladares Amparo , Álvarez Alberto M. , Ventura Juan José , Roncero Cesar , Benito Manuel , Porras Almudena 
Published: January 2014

AbstractTumor necrosis factor-α (TNFα) induces apoptosis and cell growth inhibition in primary rat fetal brown adipocytes. Here, we examine the role played by some members of the mitogen-activated protein kinase (MAPK) superfamily. TNFα activates extracellular regulated kinase-1/2 (ERK1/2) and p38MAPK. Inhibition of p38MAPK by either SB203580 or SB202190 highly reduces apoptosis induced by TNFα, whereas ERK inhibition potentiates it. Moreover, cotransfection of an active MKK3 mutant and p38MAPK induces apoptosis. p38MAPK inhibition also prevents TNFα-induced cell cycle arrest, whereas MEK1 inhibition enhances this effect, which correlates with changes in proliferating cell nuclear antigen expression, but not in cyclin D1.c-Jun and activating transcription factor-1 are potential downstream effectors of p38MAPK and ERKs upon TNFα treatment. Thus, TNFα-induced c-Jun messenger RNA expression requires ERKs activation, whereas p38MAPK inhibition enhances its expression. In addition, TNFα-induced activating transcription factor-1 phosphorylation is extensively decreased by SB203580. However, TNFα- induced NF-κB DNA-binding activity is independent of p38MAPK and ERK activation. On the other hand, C/EBP homology protein does not appear to mediate the actions of TNFα, because its expression is almost undetectable and even reduced by TNFα.Finally, although TNFα induces c-Jun N-terminal kinase (JNK) activation, transfection of a dominant negative of either JNK1 or JNK2 had no effect on TNFα-induced apoptosis. These results suggest that p38MAPK mediates TNFα-induced apoptosis and cell cycle arrest, whereas ERKs do the opposite, and JNKs play no role in this process of apoptosis.