• Title/Summary/Keyword: Metabolic Hormones

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Metabolic Engineering of the Brassinosteroid Biosynthetic Pathways (Brassinosteroid의 대사공학)

  • Lee, Mi-Ock;Song, Ki-Hong;Lee, Hyun-Kyung;Jung, Ji-Yoon;Choe, Vit-Nary;Choe, Sung-Hwa
    • Journal of Plant Biotechnology
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    • v.29 no.2
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    • pp.139-144
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    • 2002
  • Sterols play two major roles in plants: a bulk component in biological membranes and precursors of plant steroid hormones. Physiological effects of plant steroids, brassinosteroids (BRs), include cell elongation, cell division, stress tolerance, and senescence acceleration. Arabidopsis mutants that carry genetic defects in BR biosynthesis or its signaling display characteristic phenotypes, such as short robust inflorescences, dark-green round leaves, and sterility. Currently there are more than 100 dwarf mutants representing 7 genetic loci in Arabidopsis. Mutants of 6 loci, dwf1/dim1/cbb1, cpd/dwf3, dwf4, dwf5, det2/dwf6, dwf7 are rescued by exogenous application of BRs, whereas bri1/dwf2 shares phenotypes with the above 6 loci but are resistant to BRs. These suggest that the 6 loci are defective in BR biosynthesis, and the one locus is in BR signaling. Biochemical analyses, such as intermediate feeding tests, examining the levels of endogenous BR, and molecular cloning of the genes revealed that dwf7, dwf5, and dwf1 are defective in the three consecutive steps of sterol biosynthesis, from episterol to campesterol via 5-dehydroepisterol. Similarly, det2/dwf6, dwf4, and cpd /dwf3 were shown to be blocked in D$^4$reduction, 22a-hydroxylation, and 23 a-hydroxylation, respectively. A signaling mutant bril/dwf2 carries mutations in a Leucine-rich repeat receptor kinase. Interestingly, the bri1 mutant was shown to accumulate significant amount of BRs, suggesting that signaling and biosynthesis are dynamically coupled in Arabidopsis. Thus it is likely that transgenic plants over-expressing the rate-limiting step enzyme DWF4 as well as blocking its use by BRIl could dramatically increase the biosynthetic yield of BRs. When applied industrially, BRs will boost new sector of plant biotechnology because of its potential use as a precursor of human steroid hormones, a novel lead compound for cholesterol-lowering effects, and a various application in plant protection.

Radiopharmaceuticals for the Therapy of Metastatic Bone Pain (뼈전이의 방사성동위원소 통증치료)

  • Ahn, Byeong-Cheol
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.2
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    • pp.82-89
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    • 2006
  • Bone metastasis is a common sequelae of solid malignant tumors such as prostate, breast, lung, and renal cancers, which can lead to various complications, including fractures, hypercalcemia, and bone pain, as well as reduced performance status and quality of life it occurs as a result of a complex pathophysiologic process between host and tumor cells leading to cellular invasion, migration adhesion, and stimulation of osteoclastic and osteoblastic activity. Several sequelae occur as a result of osseous metastases and resulting bone pain can lead to significant debilitation. A multidisciplinary approach is usually required not only to address the etiology of the pain and its complicating factors but also to treat the patient appropriately. Pharmaceutical therapy of bone pain, includes non-steroidal analgesics, opiates, steroids, hormones, bisphosphonates, and chemotherapy. While external beam radiation therapy remains the mainstay of pain palliation of a solitary lesions, bone seeking radiopharmaceuticals have entered the therapeutic armamentarium for the treatment of multiple painful osseous lesions. $^{32}P,\;^{89}SrCl,\;^{153}Sm-EDTMP,\;^{188}Re/^{186}Re-HEDP,\;and\;^{177}Lu-EDTMP$ can be used to treat painful osseous metastases. These various radiopharmaceuticals have shown good efficacy in relieving bone pain secondary to bone metastasis. This systemic form of metabolic radiotherapy is simple to administer and complements other treatment options. This has been associated with improved mobility in many patients, reduced dependence on narcotic and non-narcotic analgesics, improved performance status and quality of life, and, in some studios, improved survival. All of these agents, although comprising different physical and chemical characteristics, offer certain advantages in that they are simple to administer, are well tolerated by the patient if used appropriately, and can be used alone or in combination with the other forms of treatment. This article illustrates the salient features of these radiopharmaceuticals, including the usual therapuetic dose, method of administration, and indications for use and also describe about the pre-management checklists, and jndication/contraindication and follow-up protocol.

Effects of a β-Adrenergic Agonist on Growth Performance and Protein Metabolism in Broilers Treated with or without an Antithyroid Substance

  • Hamano, Y.;Yamazaki, S.;Miyahara, M.;Hamada, Y.;Kobayashi, S.;Terashima, Y.
    • Asian-Australasian Journal of Animal Sciences
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    • v.12 no.5
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    • pp.788-793
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    • 1999
  • To determine the interrelationship between thyroid status and the reparitioning action of clenbuterol (CLE) in broilers, two-week-old female chickens were fed diets containing an antithyroid substance, propylthiouracil (PTU, 0 or 0.3%), CLE (0 to 1 mg/kg), or both for 18 days in a $2{\times}2$ factorial design experiment. Muscle weights (breast muscle, gastrocnemius and peroneus longus) increased only in the normal chickens fed CLE. As absolute mass, protein of leg muscle quantitatively increased in the CLE-fed normal birds. In contrast, inhibition of the CLE-induced protein accretion, especially of peroneus longus, occurred in the PTU group. A quantitative increase in DNA was observed in leg muscles of the normal chickens, but no DNA response to CLE was shown in the PTU-treated chickens. The decreased RNA in leg muscles of the PTU group was more reduced by CLE feeding. Although not statistically significant, the reduced degradation rate of whole muscle protein in normal chickens fed CLE was not confirmed in the PTU-fed group. The present study, therefore, concluded that metabolic action of thyroid hormones was a prerequisite for the hypertrophic effect of ${\beta}$-agonist in broilers.

Technical and clinical aspects of cortisol as a biochemical marker of chronic stress

  • Lee, Do Yup;Kim, Eosu;Choi, Man Ho
    • BMB Reports
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    • v.48 no.4
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    • pp.209-216
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    • 2015
  • Stress is now recognized as a universal premorbid factor associated with many risk factors of various chronic diseases. Acute stress may induce an individual's adaptive response to environmental demands. However, chronic, excessive stress causes cumulative negative impacts on health outcomes through "allostatic load". Thus, monitoring the quantified levels of long-term stress mediators would provide a timely opportunity for prevention or earlier intervention of stressrelated chronic illnesses. Although either acute or chronic stress could be quantified through measurement of changes in physiological parameters such as heart rate, blood pressure, and levels of various metabolic hormones, it is still elusive to interpret whether the changes in circulating levels of stress mediators such as cortisol can reflect the acute, chronic, or diurnal variations. Both serum and salivary cortisol levels reveal acute changes at a single point in time, but the overall long-term systemic cortisol exposure is difficult to evaluate due to circadian variations and its protein-binding capacity. Scalp hair has a fairy predictable growth rate of approximately 1 cm/month, and the most 1 cm segment approximates the last month's cortisol production as the mean value. The analysis of cortisol in hair is a highly promising technique for the retrospective assessment of chronic stress. [BMB Reports 2015; 48(4): 209-216]

The Relationship between Serum Ferritin and Bone Mineral Density

  • Jo, Yoon-Kyung;Seok, Ju-Won;Kim, Jung-Ha
    • Biomedical Science Letters
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    • v.16 no.4
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    • pp.293-298
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    • 2010
  • Several risk factors for osteoporosis are known relatively well. Some nutrients are directly or indirectly needed for metabolic processes related to bone. Recently, an increased prevalence of osteoporosis has been reported in patients with hemochromatosis, an iron overload disease. Thus, the aim of this study was to find out if there was any relationship between serum ferritin and T-score of bone mineral density in healthy women. We recruited 1,101 subjects females aged between 39 and 85 years. We measured serum ferritin, glucose tolerance indices, lipid profiles, inflammatory indices, hormones, calcium, alkaline phosphatase. Also, anthropometric, blood pressure, and bone mineral density measurements were performed. T-score was negatively correlated with age (r=-0.425; P<0.01), systolic (r=-0.109; P<0.01) and diastolic (r=-0.093; P<0.01) pressure, follicular stimulation hormone (r=-0.190; P<0.01), alkaline phosphatase (r=-0.235; P<0.01), and serum ferritin (r=-0.090; P<0.05) and positively with body mass index (r=0.050; P=0.01), HDL-cholesterol (r=0.314; P<0.01), and estradiol (r=0.200; P<0.01). After adjustment for age, alkaline phosphatase, body mass index, HDL-cholesterol, estradiol, and follicular stimulation hormone, serum ferritin was independently inversely correlated with T-score (${\beta}$=-0.001; P<0.05). It is possible that an increase of serum ferritin in females be risk to osteoporosis.

Daily Profiles of Blood Insulin, Insulin-Like Growth Factor-I, Thyroxine and Triiodothyronine in Ewes Under Three Levels of Feed Intake

  • Caldeira, R.M.;Vasques, M.I.;Vaz Portugal, A.
    • Asian-Australasian Journal of Animal Sciences
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    • v.13 no.8
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    • pp.1121-1126
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    • 2000
  • Daily variation in the serum concentrations of insulin and insulin-like growth factor-I and in the plasma concentrations of thyroxine and triiodothyronine were evaluated in ewes fed 30%, 100% and 200% of theoretical maintenance energy requirements. The single daily meal has had significant effects (p<0.05) on almost all profiles. In general, serum or plasma hormone concentrations have increased after the meal, in particular at the two higher levels of energy intake. In the group submitted to the lowest level of energy intake, the consequences of the meal on circulating levels were almost imperceptible. The effects of feeding levels on serum or plasma concentrations have widely varied among hormones, not showing any objective pattern or relationship. Because these variations may affect the interpretation of these blood indicators, knowledge of daily profiles and of the effect of feed level must be considered. In order to maximize the diagnostic value of those indicators, the most suitable times for blood collection seem to be 16 h after the meal and (or) just before the meal. The collection 16 h after the meal apparently allows the characterization of a relatively steady metabolic state, intermediate between the close effects of food intake and the final phase of the intensification of body reserves mobilization. The collection just before the meal will give a good indication of the level of activity of those mobilization mechanisms.

IL-2-enhanced NK Cell Cytotoxicity is Regulated by Adiponectin from Hypothalamo-pituitary-adrenal Axis (Adiponectin에 의한 IL-2 증가 자연살해세포 독성의 조절)

  • Kim, Keun-Young;Yang, Young
    • IMMUNE NETWORK
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    • v.6 no.1
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    • pp.6-12
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    • 2006
  • Background: The Hypothalamo-Pituitary-Adrenal (HPA) axis is an important regulator for the body's stress response. As a primary stress responsive system, HPA-axis secretes various neurotransmitters, hormones, and cytokines, which regulates the immune system. Natural killer (NK) cell which is plays an important role in the innate immune response, is specially decreased their numbers and loose cytolytic activity in response to stress. However, the effect of HPA-axis secreted proteins on NK cell activity has not been defined. Herein, we studied the effect of adrenal secreted adiponectin on NK cell cytotoxicity. Adiponectin which is well-known metabolic control protein, plays important roles in various diseases, including hypertension, cardiovascular diseases, inflammatory disorders, and cancer. Methods: Signal sequence trap was used to find stress novel secretory protein from HP A-axis. Selected adiponectin was treated mouse mature primary NK cells and then examined the effect of adiponectin to NK cell cytotoxicity and cytokine expression level. Results: We found that adiponectin which is secreted from adrenal gland, suppress IL-2 induced NK cell cytotoxicity. And also investigated cytolytic cytokines are suppressed by adiponectin. Conclusion: These data suggest that adiponectin inhibites NK cell cytotoxicity via suppression of cytotoxicity related target gene.

Anti-Obesity Drugs: A Current Research Insight

  • Son Eun-hwa;In San-Whan;Kim Byung-Oh;Pyo Suhkneung
    • Biomedical Science Letters
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    • v.11 no.2
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    • pp.89-101
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    • 2005
  • Obesity is increasing worldwide and has become a major health burden in Western societies affecting every third American and every fifth European. Obesity makes a major contribution to morbidity and mortality, predisposing individuals to cardiovascular disease and diabetes. Many new substances are currently being investigated for their usefulness in the pharmacotherapy of obesity. Most anti-obesity drugs can be divided into four groups: those that reduce food intake; those that alter metabolism; those that increase thermogenesis; and those that regulate hormone involved in feeding behavior. In this article we review these and other agents available in various countries for the treatment of obesity. Perhaps more importantly, we have focussed on areas of potential productivity in the future. Over the last 5 or so years, this impetus in obesity research has provided us with exciting new drugs targets involved in the regulation of feeding behavior and cellular mechanism involved in energy expenditure. Recent development in the quest for control of human obesity include the discovery of hormones, neuropeptides, receptors and transcription factors involved in feeding behavior, metabolic rate and adipocyte development. For developing new, perhaps even more specific pharmacological agents, further research is needed to understand the individual different genetic and physiological basis of obesity. It remains the hope of research scientists that in the not too distant future we shall see a new class of anti-obesity drugs arising logically from the molecular biology revolutions.

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Perspectives on the therapeutic potential of short-chain fatty acid receptors

  • Kim, Sunhong;Kim, Jeong-Hoon;Park, Bi Oh;Kwak, Young Shin
    • BMB Reports
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    • v.47 no.3
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    • pp.173-178
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    • 2014
  • There is rapidly growing interest in the human microbiome because of its implication in metabolic disorders and inflammatory diseases. Consequently, understanding the biology of short chain fatty acids and their receptors has become very important for identifying novel therapeutic avenues. GPR41 and GPR43 have been recognized as the cognate receptors for SCFAs and their roles in metabolism and inflammation have drawn much attention in recent years. GPR43 is highly expressed on immune cells and has been suggested to play a role in inflammatory diseases such as inflammatory bowel disease. Both GPR41 and GPR43 have been implicated in diabetes and obesity via the regulation of adipose tissue and gastrointestinal hormones. So far, many studies have provided contradictory results, and therefore further research is required to validate these receptors as drug targets. We will also discuss the synthetic modulators of GPR41 and GPR43 that are critical to understanding the functions of these receptors.

A Case Report of Severe Hypocalcemia and Hypothyroidism after Tyrosine Kinase Inhibitor Treatment (티로신키나아제 억제제 치료 후 발생한 중증 저칼슘혈증 및 갑상선기능저하증 1례)

  • Lee, Eun Kyung;Lee, Young Ki;Hwangbo, Yul;Lee, You Jin
    • International journal of thyroidology
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    • v.11 no.2
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    • pp.88-91
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    • 2018
  • After introducing tyrosine kinase inhibitors (TKIs) as promising treatments for radioactive iodine refractory advanced thyroid cancer patients, we more often meet patients with TKI-related hormone and electrolyte imbalances in clinics. Hypocalcemia associated with TKI is associated with an imbalance in calcium-vitamin D metabolism. TKI-related hypothyroidism is related to the metabolic rate of thyroid hormones. The two side effects usually occur in the early stages of TKI treatment, and if the imbalance is corrected appropriately, the effects are minor, but in severe cases, the TKI should be discontinued. The authors reported a case of severe hypocalcemia and thyroid dysfunction after TKI treatment. A 56-year-old man suffered from symptomatic hypocalcemia during TKI treatment, which was resolved after he stopped taking the TKI medication. Although calcium and vitamin D replacement have increased, hypocalcemia was recurred and TKI treatments have been permanently stopped due to serious weight loss in grade 3. After the interruption, his calcium levels normalized.