Agonistic and Antagonistic Effects of Progesterone Derivatives on the Transcriptional Activity of Nuclear Progesterone Receptor B in Yeast Model System

A. O. Michurina; A. V. Polikarpova; I. S. Levina; L. E. Kulikova; I. V. Zavarzin; A. A. Guseva; I. A. Morozov; P. M. Rubtsov; O. V. Smirnova; T. A. Shchelkunova

doi:10.1134/S0006297918050103

Agonistic and Antagonistic Effects of Progesterone Derivatives on the Transcriptional Activity of Nuclear Progesterone Receptor B in Yeast Model System

作者: Michurina A.¹, Polikarpova A.¹, Levina I.², Kulikova L.², Zavarzin I.², Guseva A.¹, Morozov I.³, Rubtsov P.³, Smirnova O.¹, Shchelkunova T.¹
隶属关系:
1. Lomonosov Moscow State University
2. Zelinsky Institute of Organic Chemistry
3. Engelhardt Institute of Molecular Biology
期: 卷 83, 编号 5 (2018)
页面: 574-585
栏目: Article
URL: https://journals.rcsi.science/0006-2979/article/view/151658
DOI: https://doi.org/10.1134/S0006297918050103
ID: 151658

如何引用文章

全文:

开放存取

##reader.subscriptionAccessGranted##
受限制的访问

订阅存取

详细
作者简介
参考
统计

详细

Identification of progesterone selective agonists and antagonists that act through one of the nuclear progesterone receptor isoforms is of particular importance for the development of tissue-specific drugs in gynecology and anticancer therapy. Fourteen pregna-D′₆- and pregna-D′₃-pentarane progesterone derivatives with 16α,17α-cycloalkane groups and two progesterone 3-deoxyderivatives were examined for their ability to regulate transcriptional activity of human nuclear progesterone receptor isoform B (nPR-B) expressed in Saccharomyces cerevisiae yeast. Transcriptional activity of nPR-B was measured from the expression of the β-galactosidase reporter gene with a hormone-responsible element in the promoter. Among the compounds tested, two were full progesterone agonists, four were partial agonists, one compound possessed both agonistic and antagonistic activity, one compound displayed only partial antagonistic activity, and eight compounds did not show any activity. Modifications of the pentarane structure, precisely, introduction of an additional double bound in the A or B rings and/or modification at the 6th position of progesterone, lead to a switch from the complete agonistic activity to partial agonistic or mixed activities. These modifications enable progestins to act as selective modulators of progesterone receptor. Steroids with reduced A-ring and 3-ketogroups lose their ability to regulate PR-B activity. Both 3-deoxycompounds, being selective ligands of progesterone membrane receptors, do not affect PR-B activity.

关键词

progesterone receptors, steroid, pentaranes, agonists, antagonists, reporter gene analysis, transcriptional activity, Saccharomyces cerevisiae

用户名
密码
记住我

忘记您的密码?	注册

用户名
密码
记住我

忘记您的密码?	注册

Agonistic and Antagonistic Effects of Progesterone Derivatives on the Transcriptional Activity of Nuclear Progesterone Receptor B in Yeast Model System

全文:

详细

关键词

作者简介

A. Michurina

A. Polikarpova

I. Levina

L. Kulikova

I. Zavarzin

A. Guseva

I. Morozov

P. Rubtsov

O. Smirnova

T. Shchelkunova