Contraceptive progestins with androgenic properties stimulate breast epithelial cell proliferation.
Details
Serval ID
serval:BIB_CF45FDDBBAD2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Contraceptive progestins with androgenic properties stimulate breast epithelial cell proliferation.
Journal
EMBO molecular medicine
ISSN
1757-4684 (Electronic)
ISSN-L
1757-4676
Publication state
Published
Issued date
07/07/2021
Peer-reviewed
Oui
Volume
13
Number
7
Pages
e14314
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
Hormonal contraception exposes women to synthetic progesterone receptor (PR) agonists, progestins, and transiently increases breast cancer risk. How progesterone and progestins affect the breast epithelium is poorly understood because we lack adequate models to study this. We hypothesized that individual progestins differentially affect breast epithelial cell proliferation and hence breast cancer risk. Using mouse mammary tissue ex vivo, we show that testosterone-related progestins induce the PR target and mediator of PR signaling-induced cell proliferation receptor activator of NF-κB ligand (Rankl), whereas progestins with anti-androgenic properties in reporter assays do not. We develop intraductal xenografts of human breast epithelial cells from 36 women, show they remain hormone-responsive and that progesterone and the androgenic progestins, desogestrel, gestodene, and levonorgestrel, promote proliferation but the anti-androgenic, chlormadinone, and cyproterone acetate, do not. Prolonged exposure to androgenic progestins elicits hyperproliferation with cytologic changes. Androgen receptor inhibition interferes with PR agonist- and levonorgestrel-induced RANKL expression and reduces levonorgestrel-driven cell proliferation. Thus, different progestins have distinct biological activities in the breast epithelium to be considered for more informed choices in hormonal contraception.
Keywords
Androgens, Animals, Cell Proliferation, Contraceptive Agents, Mice, Progestins, androgen receptor signaling, breast cancer, hormonal contraception, progestins, xenografts
Pubmed
Web of science
Open Access
Yes
Create date
04/06/2021 17:33
Last modification date
23/11/2022 8:15