Female sex steroids: receptors and function.
Female sex steroids: receptors and function.
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发表时间：
1979
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通讯作者：
J. H. Clark;E. Peck
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作者：
J. H. Clark;E. Peck
I. 简介。- 1. 类固醇激素作用的历史方面。- 2. 类固醇受体概念的一般考虑。- II。类固醇受体表征和测量。- 1. 受体标准。- a) 有限结合能力。- b) 高亲和力。- c) 类固醇特异性。- d) 组织特异性。- e) 与生物反应的相关性。- 2. 受体参数：理论与实践。- a) 非特异性结合较大时的受体测量。- b) 通过 Scatchard 分析解释饱和参数。- 1)存在非特异性结合时受体数量的估计。- 2) 具有不同亲和力的两个特定位点。- c) 解析混合结合系统。- d) 当受体浓度大大超过反应的解离常数时受体测定。- e) 类固醇结合特异性。- 1) 竞争性与非竞争性相互作用。- 2) 竞争性结合分析：问题和解释。- f) 斯卡查德图中的钩子和曲线。- 1) 配体或受体位点的高浓度。- 2) 非平衡条件。- 3) 配体或受体位点的不稳定。- 4) 放射性稀释。- 5) 相互作用的物种。- 3. 受体状态和 3H-类固醇交换。- a) 交换理论与实践技术。- b) 类固醇交换的时间和温度。- c) 受体位点结合状态的测定。- 4. 受体测定方法。- a) 细胞质受体。- 1) 活性炭吸附程序。- 2) 羟基磷灰石程序。- 3) 硫酸鱼精蛋白沉淀法。- 4) DEAE 过滤法。- b) 核受体。- 1) 核受体-雌激素复合物的 3H-雌二醇交换。- 2) 3H-类固醇交换测定的改进。- 3) 受体-激素复合物的核结合和保留。- III。细胞区室和受体-类固醇复合物的易位。- 1. 受体的细胞质或核定位。- 2. 核偏好的证据。- 3. 细胞质受体是必要的吗？- 4. 不涉及受体的类固醇积累机制。- IV。细胞质和核受体形式的特征。- 1. 雌激素和孕激素受体的细胞质形式。- a) 蔗糖密度梯度分析。- b) 色谱和电泳分析。- c) 子宫胞质中的 II 型结合位点。- 2. 雌激素和孕激素受体的核结合。- a) 受体形式和核结合。- b) 子宫核中两种类型的雌激素结合位点。- 3. 核受体位点和核结合。- V. 核结合和生物反应。- 1. 核占据和反应。- a) 雌激素受体的核保留。- b) 早期促子宫反应和核雌激素受体的保留。- c) 晚期子宫反应和 RnE 的保留复合物。- 2. 核受体和长期核保留。- 3. 雌激素受体的亲宫反应和核保留。- 4. 子宫中核受体结合和转录事件的控制。- a) RNA 聚合酶活性。- b) 子宫中的 RNA 聚合酶起始位点。- 5. 早期和晚期子宫反应之间的相互关系。- 6. 鸡输卵管中的核结合和 RNA 转录。- 7. 鸡肝中核结合以及 RNA 和蛋白质合成的控制。- a) 鸡肝细胞核与雌激素的结合。- b) 核结合、RNA 聚合酶活性和聚合酶起始位点之间的关系。- c) 核雌激素受体与 VLDL 和血浆甘油三酯合成之间的关系。- VI。类固醇受体水平的控制和类固醇拮抗作用。- 1. 雌激素受体浓度的控制。- 2. 雌激素受体细胞质补充与生物反应的关系。- 3. 雌激素对孕酮受体的控制。- 4. 孕酮对孕酮受体控制的影响。- 5. 雌激素受体水平的控制黄体酮的作用及其与雌激素拮抗作用的关系。- a) 受体补充。- b) 受体-雌激素复合物的核积累和保留。- c) 成年大鼠子宫中黄体酮对雌激素受体的拮抗作用。- 6. 雌三醇和其他短效雌激素对雌二醇的拮抗作用。- a) 雌三醇对细胞质补充的影响雌激素受体。- b) 雌三醇对 RnE2 保留和子宫生长的影响。- 7. 三苯乙烯衍生物和雌激素拮抗作用。- a) 三苯乙烯衍生物对子宫生长的影响。- b) 抗雌激素对雌激素受体细胞质补充和核保留的影响。- c) 三苯乙烯衍生物和分化细胞刺激。- 8. 类固醇拮抗作用和激素效力的一般考虑。- a) 雌激素激动剂和拮抗剂的分类。- b) 短效和长效雌激素激动剂和拮抗剂的生物学意义。- c) 剂量反应曲线、雌激素效力和受体占有率。- VII．类固醇激素和肿瘤。- 1. 雌激素和癌症。- 2. 三苯乙烯衍生物、雌激素过多和生殖道癌症。- 3. 雌激素过多和核体形成。- 4. 类固醇受体和肿瘤。- a) 雌激素依赖性生长。- b) 雌激素和黄体酮受体的相互作用。- c) 雌激素非依赖性成长.- VIII.生理关系和类固醇受体结合。- 1. 血液结合和类固醇代谢。- 2. 发育过程中的类固醇受体。- a) 雌激素受体和子宫发育。- b) 禽类输卵管发育过程中的雌激素受体。- 3. 生殖周期中的类固醇受体结合。- a) 卵巢中的受体结合。- b) 卵巢中的类固醇受体子宫和垂体。- 1) 雌激素受体。- 2) 黄体酮受体。- c) 怀孕和哺乳期间类固醇受体结合。- 1) 子宫。- 2) 卵巢。- 3) 乳腺。- 4) 胎盘和胎儿。- IX。性腺类固醇和脑功能。- 1. 中枢神经系统内靶标的分布。- a) 3H-类固醇的体内摄取和保留。- b) 雌激素和孕激素受体位点的放射自显影定位。- 2. 中枢神经系统中雌激素和孕激素的细胞质受体。- 3. 雌激素受体易位至核区室。- 4. 受体含量或功能与年龄和性别相关的差异。- 5. 性腺类固醇和神经系统功能。- a) 雌激素和下丘脑 RNA 聚合酶。- b) 下丘脑对促性腺激素分泌的控制。- X. 推测和结论。- 1. 低亲和力和高亲和力类固醇受体位点的相互作用。- 2. 备用受体和激素诱导的反应。- 3. 核受体和盐不溶性受体。- 4. 受体-雌激素复合物的核加工。- 5. 稳态与生长调节类固醇激素。- 6. 结论。- a) 激素递送至靶细胞。- b) 激素与细胞质中的受体结合。- c) 受体-激素复合物的核结合和激素刺激事件。- d) 激素作用的拮抗。- e) 肿瘤和雌激素。- 7. 结语。- 参考文献。
I. Introduction.- 1. Historical Aspects of Steroid Hormone Action.- 2. General Consideration of the Steroid Receptor Concept.- II. Steroid Receptor Characterization and Measurement.- 1. Receptor Criteria.- a) Finite Binding Capacity.- b) High Affinity.- c) Steroid Specificity.- d) Tissue Specificity.- e) Correlation with Biologic Response.- 2. Receptor Parameters: Theory and Practice.- a) Receptor Measurement when Nonspecific Binding is Large.- b) Interpretation of Saturation Parameters by Scatchard Analysis.- 1) Estimates of Receptor Number in the Presence of Nonspecific Binding.- 2) Two Specific Sites with Different Affinities.- c) Resolving Mixed Binding Systems.- d) Receptor Determination when the Concentration of Receptor Greatly Exceeds the Dissociation Constant of the Reaction.- e) Steroid Binding Specificity.- 1) Competitive vs. Noncompetitive Interactions.- 2) Competitive Binding Analysis: Problems and Interpretations.- f) Hooks and Curves in Scatchard Plots.- 1) High Concentration of Ligand or Receptor Sites.- 2) Nonequilibrium Conditions.- 3) Instability of Ligand or Receptor Sites.- 4) Dilution of Radioactivity.- 5) Interacting Species.- 3. Receptor States and 3H-Steroid Exchange.- a) Exchange Techniques in Theory and Practice.- b) Time and Temperature of Steroid Exchange.- c) Determination of the Binding State of Receptor Sites.- 4. Methods of Receptor Assay.- a) Cytoplasmic Receptors.- 1) Charcoal Adsorption Procedure.- 2) Hydroxylapatite Procedure.- 3) Protamine Sulfate Precipitation Method.- 4) DEAE Filter Method.- b) Nuclear Receptors.- 1) 3H-Estradiol Exchange of Nuclear Receptor-Estrogen Complexes.- 2) Modifications of 3H-Steroid Exchange Assay.- 3) Nuclear Binding and Retention of Receptor-Hormone Complexes.- III. Cellular Compartments and Translocation of Receptor-Steroid Complexes.- 1. Cytoplasmic or Nuclear Localization of Receptors.- 2. Evidence for Nuclear Preference.- 3. Are Cytoplasmic Receptors Necessary?.- 4. Mechanisms for Steroid Accumulation not Involving Receptors.- IV. Characteristics of Cytoplasmic and Nuclear Receptor Forms.- 1. Cytoplasmic Forms of Estrogen and Progesterone Receptors.- a) Sucrose Density Gradient Analysis.- b) Chromatographic and Electrophoretic Analysis.- c) Type II Binding Sites in Uterine Cytosol.- 2. Nuclear Binding of Estrogen and Progesterone Receptors.- a) Receptor Forms and Nuclear Binding.- b) Two Types of Estrogen Binding Sites in Uterine Nuclei.- 3. Nuclear Acceptor Sites and Nuclear Binding.- V. Nuclear Binding and Biologic Response.- 1. Nuclear Occupancy and Response.- a) Nuclear Retention of the Estrogen Receptor.- b) Early Uterotropic Responses and the Retention of Nuclear Estrogen Receptor.- c) Late Uterotropic Responses and the Retention of RnE Complexes.- 2. Nuclear Acceptors and Long-Term Nuclear Retention.- 3. Uterotropic Response and Nuclear Retention of the Estrogen Receptor.- 4. Nuclear Receptor Binding and the Control of Transcriptional Events in the Uterus.- a) RNA Polymerase Activity.- b) RNA Polymerase Initiation Sites in the Uterus.- 5. Interrelationships Between Early and Late Uterotropic Responses.- 6. Nuclear Binding and RNA Transcription in the Chick Oviduct.- 7. Nuclear Binding and the Control of RNA and Protein Synthesis in the Chicken Liver.- a) Binding of Estrogen by Chick Liver Nuclei.- b) Relationship Between Nuclear Binding, RNA Polymerase Activity, and Polymerase Initiation Sites.- c) Relationship Between Nuclear Estrogen Receptor and the Synthesis of VLDL and Plasma Triglycerides.- VI. Control of Steroid Receptor Levels and Steroid Antagonism.- 1. Control of Estrogen Receptor Concentrations.- 2. The Relationship of Cytoplasmic Replenishment of the Estrogen Receptor to Biologic Response.- 3. Control of the Progesterone Receptor by Estrogen.- 4. Effects of Progesterone on the Control of Progesterone Receptor.- 5. Control of Estrogen Receptor Levels by Progesterone and Its Relationship to Estrogen Antagonism.- a) Receptor Replenishment.- b) Nuclear Accumulation and Retention of the Receptor-Estrogen Complex.- c) Antagonism of Estrogen Receptor by Progesterone in the Adult Rat Uterus.- 6. Estradiol Antagonism by Estriol and Other Short-Acting Estrogens.- a) Effects of Estriol on Replenishment of the Cytoplasmic Estrogen Receptor.- b) Estriol Effects on RnE2 Retention and Uterine Growth.- 7. Triphenylethylene Derivatives and Estrogen Antagonism.- a) Effects of Triphenylethylene Derivatives on Uterine Growth.- b) Effects of Anti-Estrogens on Cytoplasmic Replenishment and Nuclear Retention of Estrogen Receptors.- c) Triphenylethylene Derivatives and Differential Cell Stimulation.- 8. General Considerations of Steroid Antagonism and Hormone Potency.- a) Classification of Estrogen Agonists and Antagonists.- b) Biologic Implications of Short- and Long-Acting Estrogen Agonists and Antagonists.- c) Dose Response Curves, Estrogen Potency, and Receptor Occupancy.- VII. Steroid Hormones and Neoplasia.- 1. Estrogens and Cancer.- 2. Triphenylethylene Derivatives, Hyperestrogenization, and Reproductive-Tract Cancer.- 3. Hyperestrogenization and Nuclear Body Formation.- 4. Steroid Receptors and Neoplasia.- a) Estrogen-Dependent Growth.- b) Interactions of Estrogen and Progesterone Receptors.- c) Estrogen-Independent Growth.- VIII. Physiologic Relationships and Steroid Receptor Binding.- 1. Blood Binding and Metabolism of Steroids.- 2. Steroid Receptors During Development.- a) Estrogen Receptors and Uterine Development.- b) Estrogen Receptors During Avian Oviduct Development.- 3. Steroid Receptor Binding During the Reproductive Cycle.- a) Receptor Binding in the Ovary.- b) Steroid Receptors in the Uterus and Pituitary.- 1) Estrogen Receptor.- 2) Progesterone Receptor.- c) Steroid Receptor Binding During Pregnancy and Lactation.- 1) Uterus.- 2) Ovary.- 3) Mammary Gland.- 4) Placenta and Fetus.- IX. Gonadal Steroids and Brain Function.- 1. Distribution of Targets Within the Central Nervous System.- a) In Vivo Uptake and Retention of 3H-Steroid.- b) Autoradiographic Localization of Estrogen and Progesterone Receptive Sites.- 2. Cytoplasmic Receptors for Estrogens and Progestins in the Central Nervous System.- 3. Translocation of Estrogen Receptors to Nuclear Compartments.- 4. Age- and Sex-Related Differences in Receptor Content or Function.- 5. Gonadal Steroids and Nervous System Function.- a) Estrogens and Hypothalamic RNA Polymerases.- b) Hypothalamic Control of Gonadotropin Secretion.- X. Speculations and Conclusions.- 1. Interplay of Low-and High-Affinity Steroid Receptive Sites.- 2. Spare Receptors and Hormone-Induced Responses.- 3. Nuclear Acceptors and Salt-Insoluble Receptors.- 4. Nuclear Processing of the Receptor-Estrogen Complex.- 5. Homeostatic vs. Growth-Regulating Steroid Hormones.- 6. Conclusions.- a) Hormone Delivery to Target Cells.- b) Hormone Binding to Receptors in the Cytoplasm.- c) Nuclear Binding of Receptor-Hormone Complexes and Hormone-Stimulated Events.- d) Antagonism of Hormone Action.- e) Neoplasia and Estrogens.- 7. Epilogue.- References.