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MOLECULAR MECHANISM FOR THE CONTROL OF AROMATASE IN MEN

控制男性芳香酶的分子机制

基本信息

批准号：
3233646
负责人：
GARY DAVID BERKOVITZ
金额：
$ 14.98万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-04-01 至 1990-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3233646
关键词：
androgens cyclic AMP enzyme mechanism estrogens gynecomastia hormone binding protein hormone metabolism hormone regulation /control mechanism human tissue male molecular pathology prostate disorder pseudohermaphroditism reproductive development scintillation spectrometry tissue /cell culture

项目摘要

The purpose of this project is to investigate the factors which regulate aromatase activity in order to better understand the physiology and pathology of male sexual development. The previously proposed role of estrogens in the pathogenesis of male pseudohermaphroditism, pubertal gynecomastia, benign prostatic hypertrophy, and male infertility underline the importance of studying the regulation of estrogen production. More than 80% of the circulating estrogens in normal men is derived from conversion of androgens by aromatase in extraglandular tissues. Although in vivo studies provide considerable information about the kinetics of aromatization, cell culture of tissues that are important sites of aromatization provides a unique opportunity for the study of factor which regulate the enzyme. Hence, other workers have focused on the aromatase in fibroblasts derived from adipose tissue. Recent studies in our laboratory demonstrted that the kinetics of aromatase in skin and adipose tissue fibroblasts were similar, suggesting that skin contributes to the total production of estrogens in men. Furthermore, our studies demonstrated that the regulation of aromatase in skin fibroblasts is somewhat different from from that previously described for adipose tissue cells. Therefore, the investigation of the regulation of aromatase in human skin fibroblasts grown in cell culture should provide new and valuable insights regarding the control of this enzyme. The purpose of this application will first be to define the factors which modulate baseline aromatase activity: site of skin biopsy, age of donor, plating density and passage number. Then, we will exlore the molecular mechanisms responsible for two patterns of regulation that we recently observed; the biphasic change in aromatase activity following glucocorticoid stimulation and the suppressive effects of androgens. In addition, we will compare the effects of cAMP and of steroid hormones on aromatase activity. Finally, we plan to investigate the factors responsible for the elevated levels of aromatase activity of skin fibroblasts derived from the members of an unusual kindred with familial gynecomastia due to elevated extra-glandular aromatase activity. Attempts will be made to determine the genetic transmission of this trait by studying clonal cell populations.

该项目的目的是调查调节因素芳香酶活性，以便更好地了解生理学和男性性发育的病理学。之前提议的角色雌激素在男性假两性畸形、青春期发病机制中的作用男性乳房发育症、良性前列腺肥大和男性不育症强调研究雌激素产生调节的重要性。更多的正常男性循环中80%以上的雌激素来自腺外组织中芳香酶转化雄激素。虽然体内研究提供了有关动力学的大量信息芳构化，组织的细胞培养，是重要位点芳构化为研究以下因素提供了独特的机会：调节酶。因此，其他研究人员将注意力集中在芳香酶上源自脂肪组织的成纤维细胞。我们实验室的最新研究证明皮肤和脂肪组织中芳香酶的动力学成纤维细胞相似，表明皮肤对总男性体内雌激素的产生。此外，我们的研究表明皮肤成纤维细胞中芳香酶的调节与来自之前描述的脂肪组织细胞。因此，人皮肤成纤维细胞芳香酶调控的研究在细胞培养中生长应该提供关于以下方面的新的和有价值的见解：对这种酶的控制。该应用程序的目的首先是定义影响因素调节基线芳香酶活性：皮肤活检部位、供体年龄、电镀密度和传代次数。然后，我们将探讨分子负责我们最近提出的两种监管模式的机制观察到；芳香酶活性的双相变化糖皮质激素的刺激和雄激素的抑制作用。在此外，我们将比较 cAMP 和类固醇激素对芳香酶活性。最后，我们计划调查一下因素导致皮肤芳香酶活性水平升高源自具有家族血统的不寻常亲属的成纤维细胞由于腺外芳香酶活性升高而导致男性乳房发育症。尝试将通过以下方式确定该性状的遗传传递研究克隆细胞群。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Influence of cell culture conditions on aromatase activity in human genital skin fibroblasts.

细胞培养条件对人生殖器皮肤成纤维细胞芳香酶活性的影响。

DOI：
10.1007/bf02623664
发表时间：
1989
期刊：
In vitro cellular & developmental biology : journal of the Tissue Culture Association
影响因子：
0
作者：
Bisat,T;Brown,TR;Migeon,CJ;Berkovitz,GD
通讯作者：
Berkovitz,GD

Abnormal induction of aromatase activity by dexamethasone in fibroblasts from a patient with cortisol resistance.

地塞米松对皮质醇抵抗患者的成纤维细胞中芳香酶活性的异常诱导。