東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

Androgen signaling in the placenta.

Cleys, Ellane Rachael.

FindBook

Google Book

Amazon

博客來

Androgen signaling in the placenta.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Androgen signaling in the placenta./
作者:	Cleys, Ellane Rachael.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2014,
面頁冊數:	225 p.
附註:	Source: Dissertation Abstracts International, Volume: 76-01(E), Section: B.
Contained By:	Dissertation Abstracts International76-01B(E).
標題:	Molecular biology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3635594
ISBN:	9781321167313

Androgen signaling in the placenta.
Cleys, Ellane Rachael.

Androgen signaling in the placenta. - Ann Arbor : ProQuest Dissertations & Theses, 2014 - 225 p.

Source: Dissertation Abstracts International, Volume: 76-01(E), Section: B.

Thesis (Ph.D.)--Colorado State University, 2014.

This item is not available from ProQuest Dissertations & Theses.

Placental estrogen signaling is known to regulate placental trophoblast function and differentiation. However, the role of placental androgen signaling has never been investigated, despite the rise of maternal serum androgens throughout gestation. Recent findings have shown increased maternal serum androgen in patients with the placental induced disorder preeclampsia. Preeclampsia, a maternal hypertension and proteinuria condition instigated by insufficient trophoblast differentiation and invasion into maternal spiral arteries, is also associated with increased placental expression of androgen receptor and an increased risk of incidence in patients with polymorphisms in androgen receptor that decrease androgen signaling. These findings suggest a crucial role for placental androgen signaling. Moreover, research investigating androgen's role in cancer progression has shown that many androgen responsive genes regulate cell proliferation, differentiation to invasive phenotypes, and tissue vascularization, all processes necessary for normal placental development. Androgen signaling in tumor tissues is further regulated by androgen receptor complexes with histone lysine demethylases. These complexes are recruited to androgen response elements in DNA and dynamically regulate histone tail modifications for transcription initiation. This led us to the overall hypothesis that (1) androgen signaling in trophoblast cells is important for placental development, and (2) androgen receptor complexes with histone lysine demethylases in the placenta to regulate vascularization, growth and invasion factors in trophoblast cells. To test this hypothesis, we utilized a prenatal androgenization ewe model as well as human first trimester placental samples and immortalized human trophoblast cell lines. Using the prenatal androgenized ewe model, we report for the first time expression of histone lysine demethylases in the placenta. Furthermore, we showed androgen receptor complexes with histone lysine demethylases and is recruited to an androgen response elements in the 5'untranslated flanking sequence of vascular endothelial growth factor in the sheep placenta. We also report that histone lysine demethylase are present in human first trimester syncytiotrophoblast and complex with androgen receptor in immortalized trophoblasts. Additionally, we demonstrated that androgen receptor complexes with histone lysine demethylases are also present in choriocarcinoma ACH-3P and BeWo cells. Dihydrotestosterone treatment in these cells led to down-regulation of androgen responsive genes, specifically KDM3A and MMP2. Inhibition of androgen receptor through flutamide treatment altered mRNA levels for genes regulating vascularization, including HIF1alpha, PPARalpha, and PPARy. Hypoxia also decreased CYP19 levels, however, further investigation is needed to confirm dihydrotestosterone and flutamide effect on protein expression in trophoblast cells. These data suggest that histone lysine demethylases complex with androgen receptor to regulate androgen responsive genes, including those directing placental vascularization and development. However, further experiments are needed to confirm the necessity of histone lysine demethylases for targeted androgen signaling in trophoblast cells and to determine if androgen directly regulates trophoblast differentiation and invasion. These findings suggest androgen signaling may play a critical role in placental development.

ISBN: 9781321167313Subjects--Topical Terms:

517296
Molecular biology.

Androgen signaling in the placenta.
LDR:04465nmm a2200313 4500 001 2117576
005 20170530090101.5
008 180830s2014 ||||||||||||||||| ||eng d
020 $a 9781321167313
035 $a (MiAaPQ)AAI3635594
035 $a AAI3635594
040 $a MiAaPQ $c MiAaPQ
100 1 $a Cleys, Ellane Rachael. $3 3279355
245 1 0 $a Androgen signaling in the placenta.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2014
300 $a 225 p.
500 $a Source: Dissertation Abstracts International, Volume: 76-01(E), Section: B.
500 $a Advisers: Gerrit Bouma; Colin Clay.
502 $a Thesis (Ph.D.)--Colorado State University, 2014.
506 $a This item is not available from ProQuest Dissertations & Theses.
520 $a Placental estrogen signaling is known to regulate placental trophoblast function and differentiation. However, the role of placental androgen signaling has never been investigated, despite the rise of maternal serum androgens throughout gestation. Recent findings have shown increased maternal serum androgen in patients with the placental induced disorder preeclampsia. Preeclampsia, a maternal hypertension and proteinuria condition instigated by insufficient trophoblast differentiation and invasion into maternal spiral arteries, is also associated with increased placental expression of androgen receptor and an increased risk of incidence in patients with polymorphisms in androgen receptor that decrease androgen signaling. These findings suggest a crucial role for placental androgen signaling. Moreover, research investigating androgen's role in cancer progression has shown that many androgen responsive genes regulate cell proliferation, differentiation to invasive phenotypes, and tissue vascularization, all processes necessary for normal placental development. Androgen signaling in tumor tissues is further regulated by androgen receptor complexes with histone lysine demethylases. These complexes are recruited to androgen response elements in DNA and dynamically regulate histone tail modifications for transcription initiation. This led us to the overall hypothesis that (1) androgen signaling in trophoblast cells is important for placental development, and (2) androgen receptor complexes with histone lysine demethylases in the placenta to regulate vascularization, growth and invasion factors in trophoblast cells. To test this hypothesis, we utilized a prenatal androgenization ewe model as well as human first trimester placental samples and immortalized human trophoblast cell lines. Using the prenatal androgenized ewe model, we report for the first time expression of histone lysine demethylases in the placenta. Furthermore, we showed androgen receptor complexes with histone lysine demethylases and is recruited to an androgen response elements in the 5'untranslated flanking sequence of vascular endothelial growth factor in the sheep placenta. We also report that histone lysine demethylase are present in human first trimester syncytiotrophoblast and complex with androgen receptor in immortalized trophoblasts. Additionally, we demonstrated that androgen receptor complexes with histone lysine demethylases are also present in choriocarcinoma ACH-3P and BeWo cells. Dihydrotestosterone treatment in these cells led to down-regulation of androgen responsive genes, specifically KDM3A and MMP2. Inhibition of androgen receptor through flutamide treatment altered mRNA levels for genes regulating vascularization, including HIF1alpha, PPARalpha, and PPARy. Hypoxia also decreased CYP19 levels, however, further investigation is needed to confirm dihydrotestosterone and flutamide effect on protein expression in trophoblast cells. These data suggest that histone lysine demethylases complex with androgen receptor to regulate androgen responsive genes, including those directing placental vascularization and development. However, further experiments are needed to confirm the necessity of histone lysine demethylases for targeted androgen signaling in trophoblast cells and to determine if androgen directly regulates trophoblast differentiation and invasion. These findings suggest androgen signaling may play a critical role in placental development.
590 $a School code: 0053.
650 4 $a Molecular biology. $3 517296
650 4 $a Endocrinology. $3 610914
650 4 $a Obstetrics. $3 634501
690 $a 0307
690 $a 0409
690 $a 0380
710 2 $a Colorado State University. $b Biomedical Sciences. $3 3279356
773 0 $t Dissertation Abstracts International $g 76-01B(E).
790 $a 0053
791 $a Ph.D.
792 $a 2014
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3635594