REGULATION OF STEROID HORMONE RECEPTOR ACTIVITY

类固醇激素受体活性的调节

• 批准号: 3152407
• 负责人: THOMAS G. MULDOON
• 金额: $ 7.3万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-04-01 至 1988-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3152407
• 关键词: androgens; bromocriptine; calcium; cyclic GMP; electrofocusing; estradiol; estrogen inhibitor; hormone analog; hormone regulation /control mechanism; luteinizing hormone; mammary gland; pituitary gland; prolactin; pyridoxal phosphate; radiotracer; steroid hormone biosynthesis; ultracentrifugation; uterus disorder

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.

雌激素作用的几个方面的机制处理调节