Transcription regulation of human gonadotropin-releasing hormone receptor gene expression
department or school: Medicine, Faculty of
department or school: Obstetrics and Gynaecology, Department of
data provider: DSpace
degree campus: UBCV
creator: Cheng, Kwai Wa
issued: 2009-09-18T23:48:16Z
issued: 2000
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Human placental GnRHR cDNA isolated from human choriocarcinoma JEG-3 cells, immortalized human extravillous trophoblasts (IEVT) and primary culture of cytotrophoblasts was identical to the pituitary counterpart. In addition, placental GnRHR wasshown coupling to both the protein kinase C (PKC) and protein kinase A (PKA) signaling transduction pathways. Interestingly, homologous down-regulation of GnRHR mRNA level was not observed in placental cells as in pituitary cells, suggesting that a different regulatory mechanism may exist in controlling the expression of this gene in these two tissues. UsingJEG-3 and IEVT cells as models, an upstream promoter was shown to confer the placental cell-specific expression of hGnRHR gene both in vitro and in vivo. Four putative transcription factor binding sites, namely hGR-Oct-1, hGR-CRE, hGR-GATA and hGR-AP-1, were located and confirmed to be essential for the placental expression of this gene. Importantly, hGR-CRE and hGR-GATA motifs were subsequently found to be placenta specific. A differential regulation of human GnRHR promoter activity by progesterone (P) in the pituitary and placenta was observed. P treatment decreased the promoter activity at the level of pituitary. In contrast, P stimulated the expression of this gene in the placenta. A progesterone response element, namely hGR-PRE, mediated the P-action. Interestingly, human progesterone receptor (PR)-B exhibits a cell-dependent transcriptional activity, such that it functions as a transcription activator in the placenta but a transcription repressor in the pituitary. In contrast, human PR-A acts as a transcription repressor in both tissues. The increase in hGnRHR promoter activity after cAMP/PKA pathway activation by either pharmacological agents or by PACAP and hCG in the pituitary and placenta, respectively, implies that any hormones, which activate cAMP/PKA pathway, may increase the hGnRHR gene transcription. Two elements, namely hGR-AP/CRE-1 and -2, were subsequently…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/12897
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note: T R A N S C R I P T I O N R E G U L A T I O N O F H U M A N GONADOTROPIN-RELEASING H O R M O N E R E C E P T O R G E N E E X P R E S S I O N By K W A I WA CHENG B. Sc, (Hons.), Hong Kong Baptist University, 1992 M.Pfait The University of Hong Kong, 1996 A THESIS SUBMITTED IN PARTIAL F U L F I L L M E N T OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE F A C U L T Y OF G R A D U A T E STUDIES Department of Obstetrics and Gynecology Reproductive and Developmental Science Graduate Program We accept this thesis as conforming To the required standard THE UNIVERSITY OF BRITISH C O L U M B I A November 2000 © Kwai Wa Cheng, 2000 In presenting this thesis in partial fulfilment of the requirements for an advanced degree at the University of British Columbia, I agree that the Library shall make it freely available for reference and study. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the head of my department or by his or her representatives. It is understood that copying or publication of this thesis for financial gain shall not be allowed without my written permission. The University of British Columbia Vancouver, Canada Date DE-6 (2/88) A B S T R A C T Human placental GnRHR cDNA isolated from human choriocarcinoma JEG-3 cells, immortalized human extravillous trophoblasts (IEVT) and primary culture of cytotrophoblasts was identical to the pituitary counterpart. In addition, placental GnRHR was shown coupling to both the protein kinase C (PKC) and protein kinase A (PKA) signaling transduction pathways. Interestingly, homologous down-regulation of GnRHR mRNA level was not observed in placental cells as in pituitary cells, suggesting that a different regulatory mechanism may exist in controlling the expression of this gene in these two tissues. Using JEG-3 and IEVT cells as models, an upstream promoter was shown to confer the placental cell-specific expression of hGnRHR gene both in vitro and in …
has type: Thesis/Dissertation
date issued: 2000-11
is shown at: 10.14288/1.0090601
language: eng
degree discipline: Reproductive and Developmental Sciences
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/12897