Androgens Upregulate Endometrial Epithelial Progesterone Receptor Expression: Potential Implications for Endometriosis

Samir N. Babayev, Chan Woo Park, Patrick W. Keller, Bruce R. Carr, Ruth A. Word, Orhan Bukulmez

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Androgenic compounds have been implicated in induction of endometrial atrophy yet the mechanisms of androgen effects on human endometrium have not been well studied. We hypothesized that androgens may promote their endometrial effects via modulation of progesterone receptor (PR) expression. Methods: Proliferative phase endometrial samples were collected at the time of hysterectomy. We evaluated the effect of the potent androgen 5α-dihydrotestosterone (DHT) on endometrial PR expression by treating human endometrial explants, endometrial stromal cells, and Ishikawa cells with DHT. Ishikawa cells were also treated with DHT ± the androgen receptor (AR) blocker flutamide. The PR-B, total PR messenger RNA (mRNA), and PR protein expression were assessed. Expression of cyclin D1 and D2 was checked as markers of cell proliferation. Results: As expected, estradiol induced PR expression in isolated stromal cells, endometrial epithelial cells, and tissue explants. The DHT treatment also resulted in increased PR expression in endometrial explants and Ishikawa cells but not in stromal cells. Further, protein levels of both nuclear PR isoforms (PR-A and PR-B) were induced with the DHT treatment. Although flutamide treatment alone did not affect PR expression, flutamide diminished androgen-induced upregulation of PR in both endometrial explants and Ishikawa cells. Although estradiol induced both cyclin D1 and cyclin D2 mRNA, DHT did not induce these markers of cell proliferation. Conclusion: Androgens may mediate endometrial effects through upregulation of PR gene and protein expression. Endometrial PR upregulation by androgens is mediated, at least in part, through AR.

Original languageEnglish (US)
Pages (from-to)1454-1461
Number of pages8
JournalReproductive Sciences
Volume24
Issue number10
DOIs
StatePublished - Oct 1 2017

Fingerprint

Progesterone Receptors
Endometriosis
Androgens
Up-Regulation
Dihydrotestosterone
Flutamide
Androgen Receptors
Stromal Cells
Cyclin D2
Cyclin D1
Estradiol
Cell Proliferation
Messenger RNA
Proteins
Cytoplasmic and Nuclear Receptors
Endometrium
Hysterectomy
Atrophy
Protein Isoforms
Epithelium

Keywords

  • androgens
  • endometriosis
  • endometrium
  • progesterone receptor

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Androgens Upregulate Endometrial Epithelial Progesterone Receptor Expression : Potential Implications for Endometriosis. / Babayev, Samir N.; Park, Chan Woo; Keller, Patrick W.; Carr, Bruce R.; Word, Ruth A.; Bukulmez, Orhan.

In: Reproductive Sciences, Vol. 24, No. 10, 01.10.2017, p. 1454-1461.

Research output: Contribution to journalArticle

@article{fb0085e10a3f4a638081dc6fc747cefd,
title = "Androgens Upregulate Endometrial Epithelial Progesterone Receptor Expression: Potential Implications for Endometriosis",
abstract = "Background: Androgenic compounds have been implicated in induction of endometrial atrophy yet the mechanisms of androgen effects on human endometrium have not been well studied. We hypothesized that androgens may promote their endometrial effects via modulation of progesterone receptor (PR) expression. Methods: Proliferative phase endometrial samples were collected at the time of hysterectomy. We evaluated the effect of the potent androgen 5α-dihydrotestosterone (DHT) on endometrial PR expression by treating human endometrial explants, endometrial stromal cells, and Ishikawa cells with DHT. Ishikawa cells were also treated with DHT ± the androgen receptor (AR) blocker flutamide. The PR-B, total PR messenger RNA (mRNA), and PR protein expression were assessed. Expression of cyclin D1 and D2 was checked as markers of cell proliferation. Results: As expected, estradiol induced PR expression in isolated stromal cells, endometrial epithelial cells, and tissue explants. The DHT treatment also resulted in increased PR expression in endometrial explants and Ishikawa cells but not in stromal cells. Further, protein levels of both nuclear PR isoforms (PR-A and PR-B) were induced with the DHT treatment. Although flutamide treatment alone did not affect PR expression, flutamide diminished androgen-induced upregulation of PR in both endometrial explants and Ishikawa cells. Although estradiol induced both cyclin D1 and cyclin D2 mRNA, DHT did not induce these markers of cell proliferation. Conclusion: Androgens may mediate endometrial effects through upregulation of PR gene and protein expression. Endometrial PR upregulation by androgens is mediated, at least in part, through AR.",
keywords = "androgens, endometriosis, endometrium, progesterone receptor",
author = "Babayev, {Samir N.} and Park, {Chan Woo} and Keller, {Patrick W.} and Carr, {Bruce R.} and Word, {Ruth A.} and Orhan Bukulmez",
year = "2017",
month = "10",
day = "1",
doi = "10.1177/1933719117691145",
language = "English (US)",
volume = "24",
pages = "1454--1461",
journal = "Reproductive Sciences",
issn = "1933-7191",
publisher = "SAGE Publications Inc.",
number = "10",

}

TY - JOUR

T1 - Androgens Upregulate Endometrial Epithelial Progesterone Receptor Expression

T2 - Potential Implications for Endometriosis

AU - Babayev, Samir N.

AU - Park, Chan Woo

AU - Keller, Patrick W.

AU - Carr, Bruce R.

AU - Word, Ruth A.

AU - Bukulmez, Orhan

PY - 2017/10/1

Y1 - 2017/10/1

N2 - Background: Androgenic compounds have been implicated in induction of endometrial atrophy yet the mechanisms of androgen effects on human endometrium have not been well studied. We hypothesized that androgens may promote their endometrial effects via modulation of progesterone receptor (PR) expression. Methods: Proliferative phase endometrial samples were collected at the time of hysterectomy. We evaluated the effect of the potent androgen 5α-dihydrotestosterone (DHT) on endometrial PR expression by treating human endometrial explants, endometrial stromal cells, and Ishikawa cells with DHT. Ishikawa cells were also treated with DHT ± the androgen receptor (AR) blocker flutamide. The PR-B, total PR messenger RNA (mRNA), and PR protein expression were assessed. Expression of cyclin D1 and D2 was checked as markers of cell proliferation. Results: As expected, estradiol induced PR expression in isolated stromal cells, endometrial epithelial cells, and tissue explants. The DHT treatment also resulted in increased PR expression in endometrial explants and Ishikawa cells but not in stromal cells. Further, protein levels of both nuclear PR isoforms (PR-A and PR-B) were induced with the DHT treatment. Although flutamide treatment alone did not affect PR expression, flutamide diminished androgen-induced upregulation of PR in both endometrial explants and Ishikawa cells. Although estradiol induced both cyclin D1 and cyclin D2 mRNA, DHT did not induce these markers of cell proliferation. Conclusion: Androgens may mediate endometrial effects through upregulation of PR gene and protein expression. Endometrial PR upregulation by androgens is mediated, at least in part, through AR.

AB - Background: Androgenic compounds have been implicated in induction of endometrial atrophy yet the mechanisms of androgen effects on human endometrium have not been well studied. We hypothesized that androgens may promote their endometrial effects via modulation of progesterone receptor (PR) expression. Methods: Proliferative phase endometrial samples were collected at the time of hysterectomy. We evaluated the effect of the potent androgen 5α-dihydrotestosterone (DHT) on endometrial PR expression by treating human endometrial explants, endometrial stromal cells, and Ishikawa cells with DHT. Ishikawa cells were also treated with DHT ± the androgen receptor (AR) blocker flutamide. The PR-B, total PR messenger RNA (mRNA), and PR protein expression were assessed. Expression of cyclin D1 and D2 was checked as markers of cell proliferation. Results: As expected, estradiol induced PR expression in isolated stromal cells, endometrial epithelial cells, and tissue explants. The DHT treatment also resulted in increased PR expression in endometrial explants and Ishikawa cells but not in stromal cells. Further, protein levels of both nuclear PR isoforms (PR-A and PR-B) were induced with the DHT treatment. Although flutamide treatment alone did not affect PR expression, flutamide diminished androgen-induced upregulation of PR in both endometrial explants and Ishikawa cells. Although estradiol induced both cyclin D1 and cyclin D2 mRNA, DHT did not induce these markers of cell proliferation. Conclusion: Androgens may mediate endometrial effects through upregulation of PR gene and protein expression. Endometrial PR upregulation by androgens is mediated, at least in part, through AR.

KW - androgens

KW - endometriosis

KW - endometrium

KW - progesterone receptor

UR - http://www.scopus.com/inward/record.url?scp=85029302540&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85029302540&partnerID=8YFLogxK

U2 - 10.1177/1933719117691145

DO - 10.1177/1933719117691145

M3 - Article

C2 - 28891417

AN - SCOPUS:85029302540

VL - 24

SP - 1454

EP - 1461

JO - Reproductive Sciences

JF - Reproductive Sciences

SN - 1933-7191

IS - 10

ER -