REGULATION OF CYTOCHROME P450'S IN ADRENAL

肾上腺细胞色素 P450 的调节

• 批准号: 3239552
• 负责人: VIRGINIA H BLACK
• 金额: $ 17.15万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-02-01 至 1993-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3239552
• 关键词: adrenal glands; adrenocorticotropic hormone; androgens; animal age group; antibody; biotransformation; cytochrome P450; gender difference; guinea pigs; hydroxylation; liver metabolism; messenger RNA; methylcholanthrene; microsomes; molecular cloning; oxygenases; pituitary gonadal axis; steroid metabolism; western blottings

In the guinea pig adrenal, the zona reticularis occupies over 50% of the cortical mass in adult males. The ability of the adrenal to metabolize foreign compounds is localized to the microsomes obtained from this zone. This capacity for xenobiotic metabolism increases with age, is greater in males than in females, and is suppressed by ACTH treatment, and is male- specific. This 52K protein does not react with antibodies against known adrenal microsomal steroid hydroxylases (P45021 and P45017alpha), but does react with antibody against methylcholanthrene-induced P450s in rat liver (P450c,d). Several hepatic cytochrome P450s have been shown to hydroxylate androgens at specific sites on the sterol ring, in addition to their capacity for xenobiotic metabolism. Some of these are sex-dependent. This is the first direct indication of a sex-dependent P450 in the adrenal. Whether it is specific for metabolism of foreign compounds or has functions in as yet undescribed male-specific steroid hydroxylation needs to be determined. Its relationship to P450c,d is of particular interest since neither of these proteins is known to be sex-dependent. The inner zone localization of this male-specific cytochrome P450 places it in an ideal position to modify steroids secreted by the outer zone. Its suppression by ACTH could provide an intraadrenal regulator of total steroid output. Analysis of its regulation by gonadal and pituitary hormones needs to be investigated. It is the purpose of this proposal: (1) To define the function of this male-specific P450 in xenobiotic vs steroid metabolism. (2) To investigate regulation of this P450 by gonadal and pituitary hormones at the protein and mRNA levels. (3) To investigate the relationship of this P450 to other members of this gene superfamily by cloning and sequence analysis.

在豚鼠肾上腺中，网状带占据了50%以上的面积

项目成果

Induction of CYP1A1, but not CYP1A2, in adrenals of 3, 3'-methylcholanthrene-treated guinea pigs.

在 3, 3-甲基胆蒽处理的豚鼠的肾上腺中诱导 CYP1A1，但不诱导 CYP1A2。

• DOI: 10.1006/abbi.1998.0636
• 发表时间: 1998
• 期刊: Archives of biochemistry and biophysics.
• 作者: Black,VH;Wang,AF;Henry,M;Shaw,PM
• 通讯作者: Shaw,PM

Differential ACTH response of immunodetectable HMG CoA reductase and cytochromes P450(17 alpha) and P450(21) in guinea pig adrenal outer zone cell types, zona glomerulosa and zona fasciculata.

免疫可检测的 HMG CoA 还原酶和细胞色素 P450(17 α) 和 P450(21) 在豚鼠肾上腺外区细胞类型、球状带和束状带中的差异 ACTH 反应。

• DOI: 10.1080/07435809109027197
• 发表时间: 1991
• 期刊: Endocrine research
• 影响因子: 2.1
• 作者: Brody,RI;Black,VH
• 通讯作者: Black,VH

Immunodetectable cytochromes P450 I, II, and III in guinea pig adrenal--hormone responsiveness and relationship to capacity for xenobiotic metabolism.

豚鼠肾上腺中的免疫可检测细胞色素 P450 I、II 和 III——激素反应性及其与异生素代谢能力的关系。

• DOI: 10.1210/endo-127-3-1153
• 发表时间: 1990
• 期刊: Endocrinology
• 影响因子: 4.8
• 作者: Black,VH

Estrogen, not testosterone, creates male predominance of a P4501-related cytochrome in adult guinea pig adrenals.

雌激素，而不是睾酮，在成年豚鼠肾上腺中产生了 P4501 相关细胞色素的雄性优势。

• DOI: 10.1210/endo.135.1.8013364
• 发表时间: 1994
• 期刊: Endocrinology
• 影响因子: 4.8
• 作者: Black,VH

COSAS 2.0--a Macintosh-based stereological analysis system.

COSAS 2.0——基于Macintosh的体视学分析系统。

• DOI: 10.1006/jsbi.1996.0028
• 发表时间: 1996
• 期刊: Journal of structural biology.
• 作者: Black,VH;Rosen,S
• 通讯作者: Rosen,S