Hormonal regulation of human trophoblast differentiation: A possible role for 17β-estradiol and GnRH

S. Rama; P. Petrusz; A. J. Rao

doi:10.1016/j.mce.2003.12.016

Hormonal regulation of human trophoblast differentiation: A possible role for 17β-estradiol and GnRH

S. Rama, P. Petrusz, A. J. Rao

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

Abstract

We have examined the role of 17β-estradiol and gonadotropin releasing hormone (GnRH) in the regulation of functional differentiation in human trophoblasts. In contrast to its recognized functions as a proliferation- promoting hormone in a variety of cell types, we found that 17β-estradiol induced terminal differentiation in human trophoblastic cells, and that this event was estrogen-receptor-mediated. This process involved a loss in expression of Cyclins A2 and E, and a coincident increase in p27^Kip1. The anti-proliferative effects of 17β-estradiol were annulled by specific transforming growth factor-beta 1 (TGFβ1)-neutralizing antibody, suggesting that 17β-estradiol may mediate its growth-inhibitory actions, through TGFβ1 activity. Following exposure to Buserelin, cultured human trophoblastic cells stopped proliferating and formed functionally mature syncytiotrophoblasts. This differentiation event, that involved a drastic loss in expression of proliferating-cell-nuclear-antigen, could be blocked by Cetrorelix, suggesting the involvement of functional GnRH receptors. Preliminary studies on the characterization of the human placental GnRH receptor, indicate the presence of multiple receptor isoforms across human gestation.

Original language	English (US)
Pages (from-to)	79-94
Number of pages	16
Journal	Molecular and cellular endocrinology
Volume	218
Issue number	1-2
DOIs	https://doi.org/10.1016/j.mce.2003.12.016
State	Published - Apr 15 2004
Externally published	Yes

Keywords

17β-estradiol
E2
ER
FTP
GnRH
GnRHR
beta subunit of human chorionic gonadotropin
estrogen-receptor
first-trimester placenta
gonadotropin releasing hormone
gonadotropin releasing hormone receptor
hTERT
β-hCG

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Endocrinology

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10.1016/j.mce.2003.12.016

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title = "Hormonal regulation of human trophoblast differentiation: A possible role for 17β-estradiol and GnRH",

abstract = "We have examined the role of 17β-estradiol and gonadotropin releasing hormone (GnRH) in the regulation of functional differentiation in human trophoblasts. In contrast to its recognized functions as a proliferation- promoting hormone in a variety of cell types, we found that 17β-estradiol induced terminal differentiation in human trophoblastic cells, and that this event was estrogen-receptor-mediated. This process involved a loss in expression of Cyclins A2 and E, and a coincident increase in p27Kip1. The anti-proliferative effects of 17β-estradiol were annulled by specific transforming growth factor-beta 1 (TGFβ1)-neutralizing antibody, suggesting that 17β-estradiol may mediate its growth-inhibitory actions, through TGFβ1 activity. Following exposure to Buserelin, cultured human trophoblastic cells stopped proliferating and formed functionally mature syncytiotrophoblasts. This differentiation event, that involved a drastic loss in expression of proliferating-cell-nuclear-antigen, could be blocked by Cetrorelix, suggesting the involvement of functional GnRH receptors. Preliminary studies on the characterization of the human placental GnRH receptor, indicate the presence of multiple receptor isoforms across human gestation.",

keywords = "17β-estradiol, E2, ER, FTP, GnRH, GnRHR, beta subunit of human chorionic gonadotropin, estrogen-receptor, first-trimester placenta, gonadotropin releasing hormone, gonadotropin releasing hormone receptor, hTERT, β-hCG",

author = "S. Rama and P. Petrusz and Rao, {A. J.}",

note = "Funding Information: We are extremely grateful to Dr. Susan Fisher, Department of Stomatology, University of California, San Francisco, California, for her kind gift of the BeWo cell line. We thank Dr. P. Kondaiah and Dr. R. Dighe, Department of MRDG, IISc, and Dr. Anjali Karande, Department of Biochemistry, IISc, for their helpful suggestions, and for the generous gift of various chemicals. Many thanks to Raju for his technical assistance and to Suchithra for her support. We acknowledge the help provided by the DNA sequencing facility, IISc, Bangalore. We also thank the medical and supporting staff of Lakshmi Maternity Home, Manipal Northside Hospital and Desai Nursing Home, Bangalore, for their help in collection of human placental tissue. This study is financially supported by the Department of Science and Technology (SP/SO/B-66/2000) and ICMR-Advanced Center for Cellular and Molecular Reproduction, Government of India.",

year = "2004",

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doi = "10.1016/j.mce.2003.12.016",

language = "English (US)",

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journal = "Molecular and cellular endocrinology",

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T1 - Hormonal regulation of human trophoblast differentiation

T2 - A possible role for 17β-estradiol and GnRH

AU - Rama, S.

AU - Petrusz, P.

AU - Rao, A. J.

N1 - Funding Information: We are extremely grateful to Dr. Susan Fisher, Department of Stomatology, University of California, San Francisco, California, for her kind gift of the BeWo cell line. We thank Dr. P. Kondaiah and Dr. R. Dighe, Department of MRDG, IISc, and Dr. Anjali Karande, Department of Biochemistry, IISc, for their helpful suggestions, and for the generous gift of various chemicals. Many thanks to Raju for his technical assistance and to Suchithra for her support. We acknowledge the help provided by the DNA sequencing facility, IISc, Bangalore. We also thank the medical and supporting staff of Lakshmi Maternity Home, Manipal Northside Hospital and Desai Nursing Home, Bangalore, for their help in collection of human placental tissue. This study is financially supported by the Department of Science and Technology (SP/SO/B-66/2000) and ICMR-Advanced Center for Cellular and Molecular Reproduction, Government of India.

PY - 2004/4/15

Y1 - 2004/4/15

N2 - We have examined the role of 17β-estradiol and gonadotropin releasing hormone (GnRH) in the regulation of functional differentiation in human trophoblasts. In contrast to its recognized functions as a proliferation- promoting hormone in a variety of cell types, we found that 17β-estradiol induced terminal differentiation in human trophoblastic cells, and that this event was estrogen-receptor-mediated. This process involved a loss in expression of Cyclins A2 and E, and a coincident increase in p27Kip1. The anti-proliferative effects of 17β-estradiol were annulled by specific transforming growth factor-beta 1 (TGFβ1)-neutralizing antibody, suggesting that 17β-estradiol may mediate its growth-inhibitory actions, through TGFβ1 activity. Following exposure to Buserelin, cultured human trophoblastic cells stopped proliferating and formed functionally mature syncytiotrophoblasts. This differentiation event, that involved a drastic loss in expression of proliferating-cell-nuclear-antigen, could be blocked by Cetrorelix, suggesting the involvement of functional GnRH receptors. Preliminary studies on the characterization of the human placental GnRH receptor, indicate the presence of multiple receptor isoforms across human gestation.

AB - We have examined the role of 17β-estradiol and gonadotropin releasing hormone (GnRH) in the regulation of functional differentiation in human trophoblasts. In contrast to its recognized functions as a proliferation- promoting hormone in a variety of cell types, we found that 17β-estradiol induced terminal differentiation in human trophoblastic cells, and that this event was estrogen-receptor-mediated. This process involved a loss in expression of Cyclins A2 and E, and a coincident increase in p27Kip1. The anti-proliferative effects of 17β-estradiol were annulled by specific transforming growth factor-beta 1 (TGFβ1)-neutralizing antibody, suggesting that 17β-estradiol may mediate its growth-inhibitory actions, through TGFβ1 activity. Following exposure to Buserelin, cultured human trophoblastic cells stopped proliferating and formed functionally mature syncytiotrophoblasts. This differentiation event, that involved a drastic loss in expression of proliferating-cell-nuclear-antigen, could be blocked by Cetrorelix, suggesting the involvement of functional GnRH receptors. Preliminary studies on the characterization of the human placental GnRH receptor, indicate the presence of multiple receptor isoforms across human gestation.

KW - 17β-estradiol

KW - E2

KW - ER

KW - FTP

KW - GnRH

KW - GnRHR

KW - beta subunit of human chorionic gonadotropin

KW - estrogen-receptor

KW - first-trimester placenta

KW - gonadotropin releasing hormone

KW - gonadotropin releasing hormone receptor

KW - hTERT

KW - β-hCG

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U2 - 10.1016/j.mce.2003.12.016

DO - 10.1016/j.mce.2003.12.016

M3 - Article

C2 - 15130513

AN - SCOPUS:2342620144

SN - 0303-7207

VL - 218

SP - 79

EP - 94

JO - Molecular and cellular endocrinology

JF - Molecular and cellular endocrinology

IS - 1-2

ER -

Hormonal regulation of human trophoblast differentiation: A possible role for 17β-estradiol and GnRH

Abstract

Keywords

ASJC Scopus subject areas

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