MODE OF ACTION & SYNTHESIS OF PROGESTATIONAL HORMONES

行动方式

• 批准号: 3150768
• 负责人: HILTON A SALHANICK
• 金额: $ 12.7万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-04-01 至 1987-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3150768
• 关键词: adrenocorticotropic hormone; aminoglutethimide; chemical cleavage; corpus luteum; cytochrome P450; heme; hormone inhibitor; hormone regulation /control mechanism; human subject; menstrual cycle; pituitary gonadal axis; pregnenolone; progesterone; spectrometry; steroid hormone biosynthesis

This proposal deals with the synthesis of pregnenolone, the precursor to progesterone and its inhibition in vitro and in vivo. The in vitro studies will involve the purification and characterization of corpus luteum cytochrome P-450. The interactions at the active site will be studied by equilibrium binding, optic and paramagnetic spectral techniques with radioactive and spin-labeled substrate and inhibitor analogs. Other studies will deal with the target effects of the progesterone molecule including its binding energies and those of monosubstituted congeners. Appropriate substances of potential pharmacologic significance will be assessed further by bioassay. Purification of placental aromatase will also be undertaken and characteristics of the purified protein and its substrate and inhibitor sites will be studied.

这项建议涉及孕烯醇酮的合成，孕烯醇酮是 孕酮及其在体内外的抑制作用。体外研究将 涉及黄体细胞色素P-450的纯化和性质。 活性部位的相互作用将通过平衡结合来研究， 放射性和自旋标记的光学和顺磁光谱技术 底物和抑制剂类似物。其他研究将涉及目标 孕酮分子的作用，包括它的结合能和 单取代的同系物。具有潜在药理作用的适当物质 意义将通过生物测定进一步评估。胎盘的纯化 还将进行芳香化酶和纯化蛋白的特性研究 并对其底物和抑制剂位置进行了研究。

项目成果

Molecular interactions of progesterone analogues with rabbit uterine cytoplasmic receptor.

孕酮类似物与兔子宫细胞质受体的分子相互作用。

• 发表时间: 1982
• 期刊: The Journal of biological chemistry
• 作者: Seeley,DH;Wang,WY;Salhanick,HA
• 通讯作者: Salhanick,HA

Inhibition of iron-sulfur protein-mediated reduction of cytochrome P-450SCC by specific antibodies.

通过特异性抗体抑制铁硫蛋白介导的细胞色素 P-450SCC 还原。

• DOI: 10.1210/endo-116-5-2008
• 发表时间: 1985
• 期刊: Endocrinology
• 影响因子: 4.8
• 作者: Seeley,DH;Wolfson,AJ;Hourihan,J;Schleyer,H;Kashiwagi,K;Salhanick,HA
• 通讯作者: Salhanick,HA

Effects of cholesterol side chain cleavage inhibitors on 11 beta-hydroxylation: linkage of mitochondrial oxygenase systems.

胆固醇侧链裂解抑制剂对 11 β-羟基化的影响：线粒体加氧酶系统的连接。

• DOI: 10.1016/s0039-128x(81)90209-9
• 发表时间: 1981
• 期刊: Steroids
• 影响因子: 2.7
• 作者: Whipple,CA;Grodzicki,RL;Hourihan,J;Salhanick,HA
• 通讯作者: Salhanick,HA

Amino acid composition of cytochrome P-450scc from bovine corpus luteum.

牛黄体细胞色素 P-450scc 的氨基酸组成。

• DOI: 10.1016/s0006-291x(82)80017-x
• 发表时间: 1982
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: Kashiwagi,K;Carraway,RE;Salhanick,HA
• 通讯作者: Salhanick,HA

Temperature dependence of kinetic interactions between progesterone and the uterine cytoplasmic receptor.

黄体酮和子宫细胞质受体之间的动力学相互作用的温度依赖性。

• DOI: 10.1016/0304-4165(80)90330-x
• 发表时间: 1980
• 期刊: Biochimica et biophysica acta
• 作者: Seeley,DH;Wang,WY;Salhanick,HA
• 通讯作者: Salhanick,HA