グルココルチコイドとプロゲステロン受容体は,2つのホルモン調節プロモーターの同じ部位に結合する
Nature
|February 21, 1985
まとめ
ステロイドホルモン受容体は,グルココルチコイド受容体と同様に,遺伝子プロモーターの同様のDNA配列を認識します. これは,共有された規制要素が複数のホルモンの遺伝子発現を制御することを示唆しています.
科学分野:
- 分子生物学は分子生物学である.
- エンドクリノロジー エンドクリノロジー
- 遺伝学 遺伝学とは
背景:
- ネズミの肝臓からのグルココルチコイド受容体 (GR) は,マウス乳腺腫瘍ウイルス (MMTV) プロモーターの近くのDNA配列と相互作用し,遺伝子転送研究におけるホルモン誘導に不可欠です.
- 同様のDNA配列は,ヒトのメタロチオニンIIA遺伝子と,エストロゲン,プロゲステロン,アンドロゲンに反応する鶏のリソジーム遺伝子で特定されています.
研究 の 目的:
- 異なるステロイドホルモン受容体によって認識されるDNAの調節要素の構造的類似性を調査する.
- 共有プロモーター配列が複数のステロイドホルモンに対する遺伝子発現反応を媒介するかどうかを判断する.
主な方法:
- ネズミの肝臓で認識されるMMTVプロモーター配列を特定するための遺伝子転送実験 GR.
- 鶏のリソ酵素プロモーターの特定の塩基対の削除を含むマイクロインジェクション実験.
- 精製されたネズミの肝臓GRとウサギの子宮のプロゲステロン受容体 (PR) を用いたエクソヌクレアゼIIIの足跡測定法.
主要な成果:
- 鶏のリソ酵素プロモーターの44塩基対 (-208〜-164) の削除は,プロゲステロンおよびグルココルチコイドに依存する遺伝子発現の調整された喪失につながった.
- 精製されたネズミの肝臓GRとウサギの子宮PRは,MMTVと鶏のリゾ酵素のプロモーター領域で,類似または重複するエクソヌクレアゼIIIの足跡を生成しました.
結論:
- 異なるステロイドホルモンの規制要素は,構造的に類似している可能性があります.
- これらの発見は,共有されたDNA認識配列を通じてステロイドホルモン媒介の遺伝子調節のための共通のメカニズムを示唆しています.
関連する概念動画
Intracellular Hormone Receptors
Lipid-soluble hormones diffuse across the plasma and nuclear membrane of target cells to bind to their specific intracellular receptors. These receptors act as transcription factors that regulate gene expression and protein synthesis in the target cell
Internal Receptors
Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
Types of Receptors: Internal Receptors
Many cellular signals are hydrophilic and cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind intracellular receptors that reside within the cell cytoplasm or nucleus. Many mammalian steroid hormones and nitric oxide (NO) gas use this cell signaling mechanism.
Similar to membrane-bound receptors, the binding of a ligand to the intracellular receptor of causes a conformational change in the...
Similar to membrane-bound receptors, the binding of a ligand to the intracellular receptor of causes a conformational change in the...
GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
Transducer Mechanism: Nuclear Receptors
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Target Cell Response to Hormones
Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...


