Cortisol induces aromatase expression in human placental syncytiotrophoblasts through the cAMP/Sp1 pathway

Wangsheng Wang, Jianneng Li, Yuchun Ge, Wenjiao Li, Qun Shu, Haiyan Guan, Kaiping Yang, Leslie Myatt, Kang Sun

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

One of the dominant effects of glucocorticoids in triggering parturition in certain animal species is to drive the placental conversion of progesterone to estrogen. However, in the human placenta, estrogen is formed using dehydroepiandrosterone from the fetal adrenal glands rather than progesterone as precursor. Although aromatization of dehydroepiandrosterone is crucial in estrogen synthesis in human placenta, it is not known whether glucocorticoids affect aromatase expression. Human term placental syncytiotrophoblasts were used to examine the effect of cortisol on aromatase expression. The signaling pathway and transcription factors involved were identified in this study. Results showed that cortisol induced aromatase expression in a concentration-dependent manner, which was mediated indirectly by glucocorticoid receptor and required the participation of other proteins. The induction of aromatase by cortisol could be blocked by either specificity protein 1 (Sp1) antagonist mithramycin or knockdown of Sp1 expression. The induction of aromatase and Sp1 by cortisol could be prevented by inhibitors of the cAMP pathway, whereas activators of the cAMP pathway induced Sp1 and aromatase expression as well as Sp1 binding to aromatase promoter. Concomitantly, cortisol treatment and activation of the cAMP pathway led to increased acetylation and decreased methylation of histone 3 at the aromatase promoter. In conclusion, cortisol stimulates aromatase expression through the cAMP/Sp1 pathway in human placental syncytiotrophoblasts. These findings reveal a novel role of cortisol in increasing the local level of estrogen within the placenta that would help transform the myometrium to a contractile state, thereby contributing to a cascade of events leading to human parturition.

Original languageEnglish (US)
Pages (from-to)2012-2022
Number of pages11
JournalEndocrinology
Volume153
Issue number4
DOIs
StatePublished - Apr 2012
Externally publishedYes

Fingerprint

Aromatase
Trophoblasts
Hydrocortisone
Proteins
Estrogens
Placenta
Dehydroepiandrosterone
Glucocorticoids
Progesterone
Plicamycin
Parturition
Myometrium
Glucocorticoid Receptors
Acetylation
Adrenal Glands
Protein Binding
Histones
Methylation
Transcription Factors

ASJC Scopus subject areas

  • Endocrinology

Cite this

Cortisol induces aromatase expression in human placental syncytiotrophoblasts through the cAMP/Sp1 pathway. / Wang, Wangsheng; Li, Jianneng; Ge, Yuchun; Li, Wenjiao; Shu, Qun; Guan, Haiyan; Yang, Kaiping; Myatt, Leslie; Sun, Kang.

In: Endocrinology, Vol. 153, No. 4, 04.2012, p. 2012-2022.

Research output: Contribution to journalArticle

Wang, Wangsheng ; Li, Jianneng ; Ge, Yuchun ; Li, Wenjiao ; Shu, Qun ; Guan, Haiyan ; Yang, Kaiping ; Myatt, Leslie ; Sun, Kang. / Cortisol induces aromatase expression in human placental syncytiotrophoblasts through the cAMP/Sp1 pathway. In: Endocrinology. 2012 ; Vol. 153, No. 4. pp. 2012-2022.
@article{fcae10d4d7e942dc87e9514213e4574c,
title = "Cortisol induces aromatase expression in human placental syncytiotrophoblasts through the cAMP/Sp1 pathway",
abstract = "One of the dominant effects of glucocorticoids in triggering parturition in certain animal species is to drive the placental conversion of progesterone to estrogen. However, in the human placenta, estrogen is formed using dehydroepiandrosterone from the fetal adrenal glands rather than progesterone as precursor. Although aromatization of dehydroepiandrosterone is crucial in estrogen synthesis in human placenta, it is not known whether glucocorticoids affect aromatase expression. Human term placental syncytiotrophoblasts were used to examine the effect of cortisol on aromatase expression. The signaling pathway and transcription factors involved were identified in this study. Results showed that cortisol induced aromatase expression in a concentration-dependent manner, which was mediated indirectly by glucocorticoid receptor and required the participation of other proteins. The induction of aromatase by cortisol could be blocked by either specificity protein 1 (Sp1) antagonist mithramycin or knockdown of Sp1 expression. The induction of aromatase and Sp1 by cortisol could be prevented by inhibitors of the cAMP pathway, whereas activators of the cAMP pathway induced Sp1 and aromatase expression as well as Sp1 binding to aromatase promoter. Concomitantly, cortisol treatment and activation of the cAMP pathway led to increased acetylation and decreased methylation of histone 3 at the aromatase promoter. In conclusion, cortisol stimulates aromatase expression through the cAMP/Sp1 pathway in human placental syncytiotrophoblasts. These findings reveal a novel role of cortisol in increasing the local level of estrogen within the placenta that would help transform the myometrium to a contractile state, thereby contributing to a cascade of events leading to human parturition.",
author = "Wangsheng Wang and Jianneng Li and Yuchun Ge and Wenjiao Li and Qun Shu and Haiyan Guan and Kaiping Yang and Leslie Myatt and Kang Sun",
year = "2012",
month = "4",
doi = "10.1210/en.2011-1626",
language = "English (US)",
volume = "153",
pages = "2012--2022",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "4",

}

TY - JOUR

T1 - Cortisol induces aromatase expression in human placental syncytiotrophoblasts through the cAMP/Sp1 pathway

AU - Wang, Wangsheng

AU - Li, Jianneng

AU - Ge, Yuchun

AU - Li, Wenjiao

AU - Shu, Qun

AU - Guan, Haiyan

AU - Yang, Kaiping

AU - Myatt, Leslie

AU - Sun, Kang

PY - 2012/4

Y1 - 2012/4

N2 - One of the dominant effects of glucocorticoids in triggering parturition in certain animal species is to drive the placental conversion of progesterone to estrogen. However, in the human placenta, estrogen is formed using dehydroepiandrosterone from the fetal adrenal glands rather than progesterone as precursor. Although aromatization of dehydroepiandrosterone is crucial in estrogen synthesis in human placenta, it is not known whether glucocorticoids affect aromatase expression. Human term placental syncytiotrophoblasts were used to examine the effect of cortisol on aromatase expression. The signaling pathway and transcription factors involved were identified in this study. Results showed that cortisol induced aromatase expression in a concentration-dependent manner, which was mediated indirectly by glucocorticoid receptor and required the participation of other proteins. The induction of aromatase by cortisol could be blocked by either specificity protein 1 (Sp1) antagonist mithramycin or knockdown of Sp1 expression. The induction of aromatase and Sp1 by cortisol could be prevented by inhibitors of the cAMP pathway, whereas activators of the cAMP pathway induced Sp1 and aromatase expression as well as Sp1 binding to aromatase promoter. Concomitantly, cortisol treatment and activation of the cAMP pathway led to increased acetylation and decreased methylation of histone 3 at the aromatase promoter. In conclusion, cortisol stimulates aromatase expression through the cAMP/Sp1 pathway in human placental syncytiotrophoblasts. These findings reveal a novel role of cortisol in increasing the local level of estrogen within the placenta that would help transform the myometrium to a contractile state, thereby contributing to a cascade of events leading to human parturition.

AB - One of the dominant effects of glucocorticoids in triggering parturition in certain animal species is to drive the placental conversion of progesterone to estrogen. However, in the human placenta, estrogen is formed using dehydroepiandrosterone from the fetal adrenal glands rather than progesterone as precursor. Although aromatization of dehydroepiandrosterone is crucial in estrogen synthesis in human placenta, it is not known whether glucocorticoids affect aromatase expression. Human term placental syncytiotrophoblasts were used to examine the effect of cortisol on aromatase expression. The signaling pathway and transcription factors involved were identified in this study. Results showed that cortisol induced aromatase expression in a concentration-dependent manner, which was mediated indirectly by glucocorticoid receptor and required the participation of other proteins. The induction of aromatase by cortisol could be blocked by either specificity protein 1 (Sp1) antagonist mithramycin or knockdown of Sp1 expression. The induction of aromatase and Sp1 by cortisol could be prevented by inhibitors of the cAMP pathway, whereas activators of the cAMP pathway induced Sp1 and aromatase expression as well as Sp1 binding to aromatase promoter. Concomitantly, cortisol treatment and activation of the cAMP pathway led to increased acetylation and decreased methylation of histone 3 at the aromatase promoter. In conclusion, cortisol stimulates aromatase expression through the cAMP/Sp1 pathway in human placental syncytiotrophoblasts. These findings reveal a novel role of cortisol in increasing the local level of estrogen within the placenta that would help transform the myometrium to a contractile state, thereby contributing to a cascade of events leading to human parturition.

UR - http://www.scopus.com/inward/record.url?scp=84859387985&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859387985&partnerID=8YFLogxK

U2 - 10.1210/en.2011-1626

DO - 10.1210/en.2011-1626

M3 - Article

C2 - 22315456

AN - SCOPUS:84859387985

VL - 153

SP - 2012

EP - 2022

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 4

ER -