WordNet

to a lower intensity; "he slowly phased down the light until the stage was completely black"
soft fine feathers (同)down feather
(American football) a complete play to advance the football; "you have four downs to gain ten yards"
fine soft dense hair (as the fine short hair of cattle or deer or the wool of sheep or the undercoat of certain dogs) (同)pile
(usually plural) a rolling treeless highland with little soil
understood perfectly; "had his algebra problems down" (同)down pat, mastered
extending or moving from a higher to a lower place; "the down staircase"; "the downward course of the stream" (同)downward
spatially or metaphorically from a higher to a lower level or position; "dont fall down"; "rode the lift up and skied down"; "prices plunged downward" (同)downwards, downward, downwardly
cause to come or go down; "The policeman downed the heavily armed suspect"; "The mugger knocked down the old lady after she refused to hand over her wallet" (同)knock down, cut_down, push down, pull down
shoot at and force to come down; "the enemy landed several of our aircraft" (同)shoot down, land
away from a more central or a more northerly place; "was sent down to work at the regional office"; "worked down on the farm"; "came down for the wedding"; "flew down to Florida"
becoming progressively lower; "the down trend in the real estate market"
being or moving lower in position or less in some value; "lay face down"; "the moon is down"; "our team is down by a run"; "down by a pawn"; "the stock market is down today"
being put out by a strikeout; "two down in the bottom of the ninth"
bring down or defeat (an opponent)
from an earlier time; "the story was passed down from father to son"
in an inactive or inoperative state; "the factory went down during the strike"; "the computer went down again"
not functioning (temporarily or permanently); "we cant work because the computer is down"
paid in cash at time of purchase; "put ten dollars down on the necklace"
shut; "the shades were down"
travel or traverse (a distance); "This car does 150 miles per hour"; "We did 6 miles on our hike every day"
the syllable naming the first (tonic) note of any major scale in solmization (同)doh, ut
proceed or get along; "How is she doing in her new job?"; "How are you making out in graduate school?"; "Hes come a long way" (同)fare, make_out, come, get along
create or design, often in a certain way; "Do my room in blue"; "I did this piece in wood to express my love for the forest" (同)make
carry on or function; "We could do with a little more help around here" (同)manage
get (something) done; "I did my job" (同)perform
prescribed by or according to regulation; "regulation army equipment"
(embryology) the ability of an early embryo to continue normal development after its structure has been somehow damaged or altered
the state of being controlled or governed
the act of bringing to uniformity; making regular (同)regularization, regularisation
the act of controlling or directing according to rule; "fiscal regulations are in the hands of politicians" (同)regulating
an authoritative rule (同)ordinance
a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response
English physician who first described Downs syndrome (1828-1896) (同)John L. H. Down

PrepTutorEJDIC

(高い所から)『下へ』,降りて,地面へ / (地理・地図上)南へ,下町へ;(風・流れなどが)『下(しも)手へ』;《英》(都会・大学から)地方へ,離れて / (価格・品質・温度などが)『下がって』,(数量・スピードなどが)少なく,減じて,(濃度が)薄く / (健康・風の勢いなどが)『衰えて』,気分が沈んで / (時代などが)下がって,…に至るまで / (身分・地位が)下がって / (紙面に)書き留めて,記録して / (頭金を)現金で,即金で / 最後まで,徹底的に / しっかりと,動けないように / (高い所から)…『を下がって』;…『に沿って』;…の向こうに / …の下流に / …以来 / 《名詞の前にのみ用いて》『下りの』,下への / 《名詞の前にのみ用いて》(列車・バスなどが)下りの / 《補語にのみ用いて》下に,下がって / 《補語にのみ用いて》弱まった,おさまった;落胆した,元気のない / 《補語にのみ用いて》(勝負で)負けて,すって / 《補語にのみ用いて》《おもに米話》(野球で)アウト / …‘を'打倒する,負かす,撃ち落とす / …‘を'飲み干す,飲み込む / 下り,下降 / 《複数形で》不運,逆境
(鳥の)綿毛,うぶ毛,下羽 / (植物・果実の表面の)柔らかい毛
なだらかな草原地,丘陵地帯(特にイングランド南部の小高い白亜質の草原地the Downsを言う)
《疑問文・否定文を作る》 / 《否定命令文を作る》 / 《助動詞とbe動詞のどちらも含まない文に用いて付加疑問を作る》 / 《強意語として》 / 《文》《助動詞とbe動詞のどちらも含まない文に用いて倒置文を作る》 / 《あいづちを打つ場合に》 / 《先行する動詞またはそれを含む述部の代用》 / 《so,nor,neitherで始まる簡略文で》 / …‘を'『する』,行う,果たす / 《通例have done,時にbe doneの形で》…‘を'『終える』,済ませる / …‘を'作る,作り出す / …‘を'『処理する』,整える,片付ける / 〈学課〉‘を'『勉強する』,専攻する / 〈利益・害など〉‘を'与える,もたらす / 〈人〉‘に'『役立つ』,用が足りる(serve) / …の速度で進む,距離を行く / …‘を'見物する / 〈劇〉‘を'上演する;…‘の'役を演じる / …の役目(仕事)をする / 《おもに英》…‘を'だます,かつぐ / 《話》…をへとへとにさせる / 『する』;活動する / 《通例have done,時にbe doneの形で》(…を)『終える』,済ます《+『with』+『名』》 / 〈事が〉『運ぶ』;〈人が〉暮らしていく,健康である / 〈物が〉(…に)『間に合う』,十分である;〈人が〉(…に)役に立つ,向く《+『for』+『名』》 / 《複数形で》すべきこと / 〈C〉《おもに英》大宴会,大パーティー / 〈C〉《英話》詐欺,ぺてん
ド(全音階の第1音)
〈C〉『規則』,『規定』;法規,条例 / 〈U〉(…の)『規制』,『調整』《+『of』+『名』》 / 正規の,規定どおりの
=sense organ / 受信装置

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/04/08 20:29:40」(JST)

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[Wiki en表示]

Downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external variable. An increase of a cellular component is called upregulation.

An example of downregulation is the cellular decrease in the number of receptors to a molecule, such as a hormone or neurotransmitter, which reduces the cell's sensitivity to the molecule. This phenomenon is an example of a locally acting negative feedback mechanism.

An example of upregulation is the increased number of cytochrome P450 enzymes in liver cells when xenobiotic molecules such as dioxin are administered (resulting in greater degradation of these molecules).

Some receptor agonists may cause downregulation of their respective receptor(s), while most receptor antagonists may temporally upregulate their respective receptor(s). The disequilibrium caused by these changes often causes withdrawal when the long-term use of a medication or drug is discontinued. However, the use of certain receptor antagonists may also damage receptors faster than they upregulate (internalization of receptors due to antagonism).^{[citation needed]}

Upregulation and downregulation can also happen as a response to toxins or hormones. An example of upregulation in pregnancy is hormones that cause cells in the uterus to become more sensitive to oxytocin.

Receptor downregulation

Insulin receptor mechanism

The process of downregulation occurs when there are elevated levels of the hormone insulin in the blood. When insulin binds to its receptors on the surface of a cell, the hormone receptor complex undergoes endocytosis and is subsequently attacked by intracellular lysosomal enzymes. The internalization of the insulin molecules provides a pathway for degradation of the hormone as well as for regulation of the number of sites that are available for binding on the cell surface. At high plasma concentrations, the number of surface receptors for insulin is gradually reduced by the accelerated rate of receptor internalization and degradation brought about by increased hormonal binding. The rate of synthesis of new receptors within the endoplasmic reticulum and their insertion in the plasma membrane do not keep pace with their rate of destruction. Over time, this self-induced loss of target cell receptors for insulin reduces the target cell’s sensitivity to the elevated hormone concentration. The process of decreasing the number of receptor sites is virtually the same for all hormones; it varies only in the receptor hormone complex.

Cases

This process is illustrated by the insulin receptor sites on target cells in a person with type 2 diabetes. Due to the elevated levels of blood glucose in an overweight individual, the β-cells (islets of Langerhans) in the pancreas must release more insulin than normal to meet the demand and return the blood to homeostatic levels. The near-constant increase in blood insulin levels results from an effort to match the increase in blood glucose, which will cause receptor sites on the liver cells to downregulate and decrease the number of receptors for insulin, increasing the subject’s resistance by decreasing sensitivity to this hormone. There is also a hepatic decrease in sensitivity to insulin. This can be seen in the continuing gluconeogenesis in the liver even when blood glucose levels are elevated. This is the more common process of insulin resistance, which leads to adult-onset diabetes.

Another example can be seen in diabetes insipidus, in which the kidneys become insensitive to arginine vasopressin.

Reversal

The process of downregulation can be counteracted in the above example. A person with type 2 diabetes can increase their sensitivity to insulin through proper diet and regular exercise, resulting in weight loss; some individuals may even return to their pre-diabetic state by following such a regimen.

References

Sherwood, L. (2004). “Human Physiology From Cells to Systems, 5th Ed” (p. 680). Belmont, CA: Brooks/Cole-Thomson Learning

Wilmore, J., Costill, D. (2004). Physiology of Sport and Exercise, 3rd Ed (p. 164). Champaign, IL: Human Kinetics

External links

Down-Regulation at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. インスリン受容体の構造および機能 structure and function of the insulin receptor
2. 赤血球産生調節 regulation of erythropoiesis
3. 甲状腺ホルモンの作用 thyroid hormone action
4. 鉄のバランス調節 regulation of iron balance
5. ペプチドホルモンのシグナル伝達および調節 peptide hormone signal transduction and regulation

English Journal

Metabolic and transcriptomic changes induced in host during hypersensitive response mediated resistance in rice against the Asian rice gall midge.

Agarrwal R1, Padmakumari AP2, Bentur JS3,4, Nair S5.
Rice (New York, N.Y.).Rice (N Y).2016 Dec;9(1):5. doi: 10.1186/s12284-016-0077-6. Epub 2016 Feb 19.
BACKGROUND: An incompatible interaction between rice (Oryza sativa) and the Asian rice gall midge (AGM, Orseolia oryzae Wood-Mason), that is usually manifested through a hypersensitive response (HR), represents an intricate relationship between the resistant host and its avirulent pest. We investiga
PMID 26892000

Human amniotic fluid stem cells labeled with up-conversion nanoparticles for imaging-monitored repairing of acute lung injury.

Xu Y1, Xiang J2, Zhao H1, Liang H3, Huang J1, Li Y1, Pan J1, Zhou H1, Zhang X3, Wang JH4, Liu Z2, Wang J5.
Biomaterials.Biomaterials.2016 Sep;100:91-100. doi: 10.1016/j.biomaterials.2016.05.034. Epub 2016 May 24.
Human amniotic fluid stem (hAFS) cells have generated a great deal of excitement in cell-based therapies and regenerative medicine. Here, we examined the effect of hAFS cells labeled with dual-polymer-coated UCNP-PEG-PEI nanoparticles in a murine model of acute lung injury (ALI). We observed hAFS ce
PMID 27244692

A novel monolithic controlled delivery system of resveratrol for enhanced hepatoprotection: nanoformulation development, pharmacokinetics and pharmacodynamics.

Singh A1,2, Ahmad I1, Ahmad S3, Iqbal Z1, Ahmad FJ1.
Drug development and industrial pharmacy.Drug Dev Ind Pharm.2016 Sep;42(9):1524-1536. Epub 2016 Mar 9.
The current investigation aims to present a novel solid lipid-based nanoparticulate system of resveratrol (RV) for the effective treatment of liver cirrhosis. A simplified solvent injection method was employed and the Box-Behnken experimental design was applied for optimization to get a window parti
PMID 26902951

Japanese Journal

Relationships between gill Na+,K+-ATPase activity and endocrine and local insulin-like growth factor-I levels during smoltification of masu salmon (Oncorhynchus masou)

Shimomura Takahiro,Nakajima Takuro,Horikoshi Moeri,Iijima Anai,Urabe Hirokazu,Mizuno Shinya,Hiramatsu Naoshi,Hara Akihiko,Shimizu Munetaka
General and Comparative Endocrinology 178(2), 427-435, 2012-09-01
… Expression of two IGF-I receptor (igf1r) subtypes in the gill decreased in June, which could account for the disruption by preventing circulating IGF-I from acting on the gill and retaining it in the blood. … The present study suggests that the increase in gill NKA activity in the course of smoltification of masu salmon was supported by both endocrine and local IGF-I, and the decrease during desmoltification in freshwater was due at least in part to the down-regulation of gill IGF-I receptors. …
NAID 120004710973

The Mechanism of Calcitonin Gene-Related Peptide-Containing Nerve Innervation

HASHIKAWA HOBARA Narumi,HASHIKAWA Naoya,ZAMAMI Yoshito,TAKATORI Shingo,KAWASAKI Hiromu
Journal of pharmacological sciences 119(2), 117-121, 2012-06-20
… In apolipoprotein E–knockout mice, which have atherosclerosis and peripheral sensory nerve defects, nerve growth factor (NGF)-mediated CGRP nerve facilitation was down-regulated, which may have been caused by the impairment of the Akt–NO–cGMP pathway. … Adrenomedullin, hepatocyte growth factor, and angiotensin II type 2 receptor activation induced CGRP nerve distribution in phenol-injured rats. …
NAID 10030828329