scholarly journals Autoregulation of central and peripheral growth hormone receptor mRNA in domestic fowl

1998 ◽  
Vol 156 (2) ◽  
pp. 323-329 ◽  
Author(s):  
KL Hull ◽  
S Harvey
Keyword(s):  
Growth Hormone ◽  
Domestic Fowl ◽  
Gene Transcript ◽  
Central Administration ◽  
Systemic Injection ◽  
Peripheral Tissues ◽  
Tissue Specific ◽  
Ghr Gene ◽  
Tissue Sensitivity ◽  
The Brain

Growth hormone (GH) regulates numerous cellular functions in many different tissues. A common receptor is believed to mediate these tissue-specific effects, suggesting that post-receptor signalling molecules or tissue sensitivity to GH may differ between tissues. Tissue sensitivity depends upon the abundance of GH receptors (GHRs), thus tissue-specific GHR regulation could enable tissue-specific GH actions. The comparative autoregulation of GHR gene transcription in central (whole brain or hypothalami) and peripheral (liver, bursa, spleen and thymus) tissues was therefore examined in domestic fowl. In all tissues, a 4.4 kb GHR gene transcript that encodes the full-length GHR was identified. The abundance of this transcript was inversely related to endogenous GH status; it was lower in males with high circulating concentrations of GH and higher in females with lower basal concentrations of plasma GH. The abundance of this transcript was also rapidly downregulated in response to a bolus systemic injection of recombinant chicken GH, designed to mimic an episodic burst of endogenous GH release. This autoregulatory response was observed within 2 h of GH administration and was of greater magnitude in the brain than in peripheral tissues. Intracerebroventricular injections of GH also downregulated GHR gene expression in the brain, although hepatic GHR transcripts were unaffected 24 h after central administration of GH. In contrast, the induction of hyposomatotropism by passive GH immunoneutralization increased the abundance of the GHR transcript in the thymus, but not in other central (brain) or peripheral (bursa, liver) tissues. GH is not the sole regulator of GHR abundance, however; hypersomatropism induced by hypothyroidism was associated with an increase in GHR mRNA. The expression of the GHR gene in the domestic fowl would thus appear to be autoregulated by GH in a tissue-specific way.

scholarly journals Synaptic and epidermal accumulations of human acetylcholinesterase are encoded by alternative 3'-terminal exons.

1995 ◽  
Vol 15 (6) ◽  
pp. 2993-3002 ◽  
Author(s):  
S Seidman ◽  
M Sternfeld ◽  
R Ben Aziz-Aloya ◽  
R Timberg ◽  
D Kaufer-Nachum ◽  
...  
Keyword(s):  
Neuromuscular Junctions ◽  
Gene Transcript ◽  
Dna Encoding ◽  
Tissue Specific ◽  
Evolutionarily Conserved ◽  
Low Salt ◽  
Catalytically Active ◽  
Specific Accumulation ◽  
The Brain ◽  
Muscle Ache

Tissue-specific heterogeneity among mammalian acetylcholinesterases (AChE) has been associated with 3' alternative splicing of the primary AChE gene transcript. We have previously demonstrated that human AChE DNA encoding the brain and muscle AChE form and bearing the 3' exon E6 (ACHE-E6) induces accumulation of catalytically active AChE in myotomes and neuromuscular junctions (NMJs) of 2- and 3-day-old Xenopus embryos. Here, we explore the possibility that the 3'-terminal exons of two alternative human AChE cDNA constructs include evolutionarily conserved tissue-recognizable elements. To this end, DNAs encoding alternative human AChE mRNAs were microinjected into cleaving embryos of Xenopus laevis. In contrast to the myotomal expression demonstrated by ACHE-E6, DNA carrying intron 14 and alternative exon E5 (ACHE-I4/E5) promoted punctuated staining of epidermal cells and secretion of AChE into the external medium. Moreover, ACHE-E6-injected embryos displayed enhanced NMJ development, whereas ACHE-I4/E5-derived enzyme was conspicuously absent from muscles and NMJs and its expression in embryos had no apparent effect on NMJ development. In addition, cell-associated AChE from embryos injected with ACHE-I4/E5 DNA was biochemically distinct from that encoded by the muscle-expressible ACHE-E6, displaying higher electrophoretic mobility and greater solubility in low-salt buffer. These findings suggest that alternative 3'-terminal exons dictate tissue-specific accumulation and a particular biological role(s) of AChE, associate the 3' exon E6 with NMJ development, and indicate the existence of a putative secretory AChE form derived from the alternative I4/E5 AChE mRNA.

Site-specific modulation of LPS-induced fever and interleukin-1β expression in rats by interleukin-10

2002 ◽  
Vol 282 (6) ◽  
pp. R1762-R1772 ◽  
Author(s):  
Annemarie Ledeboer ◽  
Rob Binnekade ◽  
John J. P. Brevé ◽  
John G. J. M. Bol ◽  
Fred J. H. Tilders ◽  
...  
Keyword(s):  
Brain Stem ◽  
Interleukin 10 ◽  
Primary Site ◽  
Central Administration ◽  
Febrile Response ◽  
Peripheral Tissues ◽  
Site Specific ◽  
Intracerebroventricular Infusion ◽  
The Brain ◽  
Anti Inflammatory Cytokine

Bacterial lipopolysaccharide (LPS) induces fever that is mediated by pyrogenic cytokines such as interleukin (IL)-1β. We hypothesized that the anti-inflammatory cytokine IL-10 modulates the febrile response to LPS by suppressing the production of pyrogenic cytokines. In rats, intravenous but not intracerebroventricular infusion of IL-10 was found to attenuate fever induced by peripheral administration of LPS (10 μg/kg iv). IL-10 also suppressed LPS-induced IL-1β production in peripheral tissues and in the brain stem. In contrast, central administration of IL-10 attenuated the febrile response to central LPS (60 ng/rat icv) and decreased IL-1β production in the hypothalamus and brain stem but not in peripheral tissues and plasma. Furthermore, intravenous LPS upregulated expression of IL-10 receptor (IL-10R1) mRNA in the liver, whereas intracerebroventricular LPS enhanced IL-10R1 mRNA in the hypothalamus. We conclude that IL-10 modulates the febrile response by acting in the periphery or in the brain dependent on the primary site of inflammation and that its mechanism of action most likely involves inhibition of local IL-1β production.

scholarly journals Functional Role of c-Jun-N-Terminal Kinase in Feeding Regulation

Endocrinology ◽  
2010 ◽  
Vol 151 (2) ◽  
pp. 671-682 ◽  
Author(s):  
Elizabeth K. Unger ◽  
Merisa L. Piper ◽  
Louise E. Olofsson ◽  
Allison W. Xu
Keyword(s):  
Functional Role ◽  
Central Administration ◽  
Peripheral Tissues ◽  
Immunological Responses ◽  
Feeding Regulation ◽  
Central Inhibition ◽  
The Brain ◽  
Nuclear Immunoreactivity ◽  
Deficient Mice

c-Jun-N-terminal kinase (JNK) is a signaling molecule that is activated by proinflammatory signals, endoplasmic reticulum (ER) stress, and other environmental stressors. Although JNK has diverse effects on immunological responses and insulin resistance in peripheral tissues, a functional role for JNK in feeding regulation has not been established. In this study, we show that central inhibition of JNK activity potentiates the stimulatory effects of glucocorticoids on food intake and that this effect is abolished in mice whose agouti-related peptide (AgRP) neurons are degenerated. JNK1-deficient mice feed more upon central administration of glucocorticoids, and glucocorticoid receptor nuclear immunoreactivity is enhanced in the AgRP neurons. JNK inhibition in hypothalamic explants stimulates Agrp expression, and JNK1-deficient mice exhibit increased Agrp expression, heightened hyperphagia, and weight gain during refeeding. Our study shows that JNK1 is a novel regulator of feeding by antagonizing glucocorticoid function in AgRP neurons. Paradoxically, JNK1 mutant mice feed less and lose more weight upon central administration of insulin, suggesting that JNK1 antagonizes insulin function in the brain. Thus, JNK may integrate diverse metabolic signals and differentially regulate feeding under distinct physiological conditions.

scholarly journals Modeling temperature- and Cav3 subtype-dependent alterations in T-type calcium channel mediated burst firing

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Fernando R. Fernandez ◽  
Mircea C. Iftinca ◽  
Gerald W. Zamponi ◽  
Ray W. Turner
Keyword(s):  
Calcium Channel ◽  
Neuronal Excitability ◽  
Neuronal Firing ◽  
Mammalian Brain ◽  
Peripheral Tissues ◽  
Window Current ◽  
Modeling Data ◽  
The Brain ◽  
Firing Neuron ◽  
Cav3 Channel

AbstractT-type calcium channels are important regulators of neuronal excitability. The mammalian brain expresses three T-type channel isoforms (Cav3.1, Cav3.2 and Cav3.3) with distinct biophysical properties that are critically regulated by temperature. Here, we test the effects of how temperature affects spike output in a reduced firing neuron model expressing specific Cav3 channel isoforms. The modeling data revealed only a minimal effect on baseline spontaneous firing near rest, but a dramatic increase in rebound burst discharge frequency for Cav3.1 compared to Cav3.2 or Cav3.3 due to differences in window current or activation/recovery time constants. The reduced response by Cav3.2 could optimize its activity where it is expressed in peripheral tissues more subject to temperature variations than Cav3.1 or Cav3.3 channels expressed prominently in the brain. These tests thus reveal that aspects of neuronal firing behavior are critically dependent on both temperature and T-type calcium channel subtype.

scholarly journals Understanding Quantitative Circadian Regulations Are Crucial Towards Advancing Chronotherapy

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 883 ◽  
Author(s):  
Debajyoti Chowdhury ◽  
Chao Wang ◽  
Ai-Ping Lu ◽  
Hai-Long Zhu
Keyword(s):  
Circadian Rhythms ◽  
Molecular Mechanisms ◽  
Temporal Stability ◽  
Biological Rhythms ◽  
Integrative Approach ◽  
Peripheral Tissues ◽  
Innovative Strategies ◽  
Neural Connections ◽  
Core Components ◽  
The Brain

Circadian rhythms have a deep impact on most aspects of physiology. In most organisms, especially mammals, the biological rhythms are maintained by the indigenous circadian clockwork around geophysical time (~24-h). These rhythms originate inside cells. Several core components are interconnected through transcriptional/translational feedback loops to generate molecular oscillations. They are tightly controlled over time. Also, they exert temporal controls over many fundamental physiological activities. This helps in coordinating the body’s internal time with the external environments. The mammalian circadian clockwork is composed of a hierarchy of oscillators, which play roles at molecular, cellular, and higher levels. The master oscillation has been found to be developed at the hypothalamic suprachiasmatic nucleus in the brain. It acts as the core pacemaker and drives the transmission of the oscillation signals. These signals are distributed across different peripheral tissues through humoral and neural connections. The synchronization among the master oscillator and tissue-specific oscillators offer overall temporal stability to mammals. Recent technological advancements help us to study the circadian rhythms at dynamic scale and systems level. Here, we outline the current understanding of circadian clockwork in terms of molecular mechanisms and interdisciplinary concepts. We have also focused on the importance of the integrative approach to decode several crucial intricacies. This review indicates the emergence of such a comprehensive approach. It will essentially accelerate the circadian research with more innovative strategies, such as developing evidence-based chronotherapeutics to restore de-synchronized circadian rhythms.

Loss of tissue sensitivity to growth hormone during maternal deprivation in rats

Life Sciences ◽  
1979 ◽  
Vol 25 (24-25) ◽  
pp. 2089-2097 ◽  
Author(s):  
Cynthia M. Kuhn ◽  
Gary Evoniuk ◽  
Saul M. Schanberg
Keyword(s):  
Growth Hormone ◽  
Maternal Deprivation ◽  
Tissue Sensitivity

scholarly journals Tissue-specific distribution of cross-linked somatostatin receptor proteins in the rat

1992 ◽  
Vol 282 (2) ◽  
pp. 339-344 ◽  
Author(s):  
C B Srikant ◽  
K K Murthy ◽  
Y C Patel
Keyword(s):  
Exocrine Pancreas ◽  
Receptor Protein ◽  
Cross Linking ◽  
Molecular Heterogeneity ◽  
Dependent Manner ◽  
Tissue Specific ◽  
Receptor Proteins ◽  
Specific Distribution ◽  
A Minor ◽  
The Brain

Pharmacological studies have suggested that the somatostatin (SS) receptor is heterogeneous and exhibits SS-14-and SS-28-selective subtypes. Whether such subtypes arise from molecular heterogeneity of the receptor protein has not been definitively established. Previous reports characterizing the molecular properties of the SS receptor by the cross-linking approach have yielded divergent size estimates ranging from 27 kDa to 200 kDa. In order to resolve this discrepancy, as well as to determine whether SS-14 and SS-28 interact with specific receptor proteins, we have cross-linked radioiodinated derivatives of [125I-Tyr11]SS-14 (T*-SS-14) and [Leu8,D-Trp22,125I-Tyr25]SS-28 (LTT*-SS-28) to membrane SS receptors in rat brain, pituitary, exocrine pancreas and adrenal cortex using a number of chemical and photoaffinity cross-linking agents. The labelled cross-linked receptor proteins were analysed by SDS/PAGE under reducing conditions followed by autoradiography. Our findings indicate that the pattern of specifically labelled cross-linked SS receptor proteins is sensitive to the concentration of chemical cross-linking agents such as disuccinimidyl suberate and dithiobis-(succinimidyl propionate). Labelled high-molecular-mass complexes of cross-linked receptor-ligand proteins were observed only when high concentrations of these cross-linkers were employed. Using optimized low concentrations of cross-linkers, however, two major labelled bands of 58 +/- 3 kDa and 27 +/- 2 kDa were detected. These two bands were identified as specifically labelled SS receptor proteins subsequent to cross-linking with a number of photoaffinity cross-linking agents as well. We demonstrate here that the 58 kDa protein is the major SS receptor protein in the rat pituitary, adrenal and exocrine pancreas, whereas the 27 kDa moiety represents the principal form in the brain. Additionally, the presence of a minor specifically labelled band of 32 kDa was detected uniquely in the brain, and a minor labelled protein of 42 kDa was observed in the pancreas. The labelling pattern obtained with LTT*-SS-28 was identical to that observed with T*-SS-14. Labelling of the 27 kDa band by either ligand was inhibited by SS-14 and SS-28 in a dose-dependent manner. Densitometric quantification showed that SS-14 exhibited greater than 2-fold greater potency than SS-28 for inhibiting the labelling of the 27 kDa species. These findings emphasize the need for careful interpretation of cross-linking data obtained for SS receptors, and provide evidence for molecular heterogeneity and for a tissue-specific distribution of the two principal SS receptor proteins.

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