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Xenografted breast epithelia reveal differences in growth stimulation among contraceptive progestins related to androgenic properties [human]

ABSTRACT: Xenografted breast epithelia reveal differences in growth stimulation among contraceptive progestins related to androgenic properties [human]

PROVIDER: PRJNA649233 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12339400.fastq.gz	Fastqsanger.gz
	SRR12339392.fastq.gz	Fastqsanger.gz
	SRR12339393.fastq.gz	Fastqsanger.gz
	SRR12339394.fastq.gz	Fastqsanger.gz
	SRR12339395.fastq.gz	Fastqsanger.gz

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Xenografted breast epithelia reveal differences in growth stimulation among contraceptive progestins related to androgenic properties.

Project description:Xenografted breast epithelia reveal differences in growth stimulation among contraceptive progestins related to androgenic properties.

| PRJNA649228 | ENA

Xenografted breast epithelia reveal differences in growth stimulation among contraceptive progestins related to androgenic properties [mouse]

Project description:Xenografted breast epithelia reveal differences in growth stimulation among contraceptive progestins related to androgenic properties [mouse]

| PRJNA649234 | ENA

Xenografted breast epithelia reveal differences in growth stimulation among contraceptive progestins related to androgenic properties [mouse]

Project description:Hormonal contraception exposes women to different synthetic progesterone receptor (PR) agonists, progestins, and transiently increases breast cancer risk. How progestins affect the breast epithelium is poorly understood because we lack adequate models to study this. We hypothesized that individual progestins differentially affect cell proliferation in the normal breast epithelium and hence breast cancer risk. Using mouse mammary tissue ex vivo, we show that testosterone-related progestins strongly induce the PR target and mediator of PR signaling induced cell proliferation Receptor Activator of NF-κB Ligand (Rankl), previously implicated in breast carcinogenesis, whereas other progestins fail to do so. We developed xenografts of normal human breast epithelial cells (HBECSs) to the milk ducts of immunocompromised female mice and show that they remain hormone-responsive. Using HBECSs from 36 women, we show that testosterone-related progestins, desogestrel, gestodene, and levonorgestrel, induce PSA (KLK3) and promote their proliferation, whereas the anti-androgenic progestins, which have shown anti-androgenic properties in reporter assays, chlormadinone acetate and cyproterone acetate, do not. Pharmacological inhibition of the androgen receptor (AR) inhibits PR agonist and levonorgestrel-induced RANKL expression and both pharmacological and genetic AR inhibition reduce levonorgestrel-driven breast epithelial cell proliferation in vivo. Prolonged exposure to androgenic progestins elicits hyperproliferation with cytologic changes. Thus, different progestins have distinct biological activities in the breast epithelium that should be taken into account for more informed choices in hormonal contraception.

2021-05-12 | GSE155273 | GEO

Xenografted breast epithelia reveal differences in growth stimulation among contraceptive progestins related to androgenic properties [human]

2021-05-12 | GSE155272 | GEO

Xenografted breast epithelia reveal differences in growth stimulation among contraceptive progestins related to androgenic properties.

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-05-12 | GSE155274 | GEO

Contraceptive progestins with androgenic properties stimulate breast epithelial cell proliferation.

Project description: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.

| S-EPMC8261488 | biostudies-literature

Contraceptive progestins with androgenic properties stimulate breast epithelial cell proliferation

Project description: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-?B 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.

| S-SCDT-EMM-2021-14314P | biostudies-other

Microarray expression profile analysis of long non-coding RNA in androgenic alopecia: a study of Chinese men

Project description:To examined the genome-wide expression levels of lncRNAs in androgenic alopecia tissues and paired adjacent normal tissues by microarray analysis. We identified numerous lncRNAs that were differentially regulated between androgenic alopecia and paired normal tissues. Collected 3 pairs of male scalp androgenic alopecia tissues and adjacent normal tissues, then extracted mRNAs from the tissues and transcripted the mRNAs into cRNAs. Then, cRNAs were hybridized onto the Human LncRNA Expression Microarrays. And then analyzed the results.

2016-07-27 | E-GEOD-84839 | biostudies-arrayexpress

Comparing the androgenic and estrogenic properties of progestins used in contraception and hormone therapy.

Project description:Progestins used in endocrine therapies bind to multiple steroid receptors and are associated with several side-effects. It is thus important to understand the relationship between steroid receptor cross-reactivity and the side-effect profile of progestins. In cell lines that express negligible levels of steroid receptors, we report for the first time the binding affinities, potencies and efficacies of selected progestins from different generations determined in parallel. We show that the progestins bind to the androgen receptor (AR) with similar affinities to each other and progesterone, while none bind estrogen receptor (ER)-?, and only norethisterone acetate, levonorgestrel and gestodene bind ER?. Comparative dose-response analysis revealed that progestins from the first three generations display similar androgenic activity to the natural androgen dihydrotestosterone for transactivation, while norethisterone acetate, levonorgestrel and gestodene are ER? agonists. We show for the first time that the anti-androgenic properties of progesterone and drospirenone are similar to the well-known AR antagonist hydroxyflutamide, while nomegestrol acetate is more potent and nestorone less potent than both hydroxyflutamide and progesterone. Moreover, we are the first to report that the older progestins, unlike progesterone and the fourth generation progestins, are efficacious ER? agonists for transrepression, while the selected progestins from the second and third generation are efficacious AR agonists for transrepression. Considering the progestin potencies and their reported free serum concentrations relative to dihydrotestosterone and estradiol, our results suggest that the progestins are likely to exert AR-, but not ER?- or ER?-mediated effects in vivo.

| S-EPMC5740213 | biostudies-literature

Vaginal microbiota in response to hormonal contraceptive use

Project description:Vaginal microbiome in response to hormonal contraceptive use

| PRJEB30774 | ENA