REGULATION OF STEROID HORMONE RECEPTOR ACTIVITY

雌激素作用机制的几个方面 雌激素受体（ER）的数量和功能将被研究， 使用大鼠的子宫、肝脏、垂体前叶和下丘脑， 小鼠乳腺组织。 波动分布的总体动力学 受体将被研究作为一个功能的占用和未占用ER 在细胞内室，包括微粒体， 在施用各种类固醇激素刺激后的时间间隔。 影响 ATP和/或ATP酶、蛋白质/RNA合成抑制剂，以及剂量相关的 将评估ER处理。 将确定LH释放模式 在这些受体动力学研究的过程中。 ER受体 微粒体的能力将被探索作为一种可能的检测手段 ER复合物的差异“激活”响应结合 抗雌激素、雄激素和4-汞雌二醇（4 ME）。 4 ME的效果， 吡哆醛-5 '磷酸和雌二醇对微粒体RNP颗粒的作用， 将检查胞质溶胶起始因子的剂量和时间依赖性。 小鼠乳腺雌激素受体性质和类固醇特异性在 将在以下条件下研究对雌激素治疗的反应： 蛋白酶抑制剂，并着眼于雌酮的存在 受体的 将检测催乳素增强和抑制， 使用乳腺组织的ER和孕酮受体活性调节剂 来自MTV+和MTV品系的小鼠。 在LHRH-ER相互作用的持续研究中 在垂体前叶中，将使用分离的富含ER的促性腺激素。 钙和环鸟苷酸将作为该作用的介体进行检查，并且 将重新评估对LHRH激动剂/拮抗剂的反应动力学 在这些细胞的悬浮液或培养物中。 LHRH受体分布和 将研究微粒体组分的参与。 ER复合物激活 以各种方式排除配体结合将被评估为竞争者 3 H-雌二醇-受体复合物与DNA的结合，以测量贡献 类固醇分子本身的相互作用。 激活的复合物 将进行物理化学比较，以确定它们是否符合 不同. 嵌入剂，抗雌激素受体复合物， 雄激素受体复合物和未标记的雌二醇受体复合物将 被用作DNA结合的假定竞争者。 各种来源的 核苷酸序列，包括克隆的雌激素诱导的 将检查基因的结合特异性。 这些研究 有望有助于我们理解激素 反应性受细胞内急性或慢性变化的影响， 环境

Several aspects of the mechanism of estrogen action dealing with regulation of estrogen receptor (ER) number and functionality will be investigated, using uteri, liver, anterior pituitary and hypothalamus from rats and mammary tissue of mice. The overall dynamics of fluctuating distribution of receptors will be studied as a function of occupied and unoccupied ER species in the intracellular compartments, including microsomes, at intervals after administration of various steriod hormone stimuli. Effects of ATP and/or molybdate, protein/RNA synthesis inhibitors, and dose-related ER processing, will be assessed. LH release patterns will be determined over the course of these receptor dynamics studies. The ER acceptor capability of microsomes will be explored as a possible means of detecting differences in ER complexes "activated" in response to binding of antiestrogens, androgens and 4-mercuriestradiol (4ME). The effects of 4ME, pyridoxal-5' phosphate and estradiol on microsomal RNP particles and cytosol initiation factors will be examined for dose- and time-dependency. Differences in mouse mammary gland ER nature and steroidal specificity in response to estrogen treatment will be investigated in the presence of protease inhibitors and with an eye toward existence of an estrone receptor. Prolactin augmentation and suppression will be tested as modifiers of ER and progesterone receptor activity, using mammary tissue from MTV+ and MTV strains of mice. In continued study of LHRH-ER interplay in the anterior pituitary, isolated ER-rich gonadotropes will be used. Calcium and cGMP will be examined as mediators of the action, and the kinetics of responsiveness to LHRH agonist/antagonist will be re-evaluated in these cells in suspension or culture. LHRH receptor distribution and microsomal component involvement will be studied. ER complexes activated in various ways excluding ligand binding will be assessed as competitors of 3H-estradiol-receptor complex binding to DNA, to measure the contribution of the steroid molecule itself to the interaction. The activated complexes will be physicochemically compared to see whether they are discernibly different. Intercalating agents, antiestrogen-receptor complexes, androgen-receptor complexes and unlabeled estradiol-receptor complexes will be used as putative competitors for DNA binding. Various sources of nucleotide sequences, including fragments of cloned estrogen-inducible genes, will be examined for binding specificity. These studies are expected to contribute to our understanding of the ways in which hormone responsiveness is subject to acute or chronic changes in the cellular environment.