The role of parathyroid hormone-related peptide (PTH-rP) in the regulation of proliferation in trophoblast using choriocarcinoma JAR as a model
The role of parathyroid hormone-related peptide (PTH-rP) in the regulation of proliferation in trophoblast using choriocarcinoma JAR as a model
The effects of EGF, PTH-rP amide and PTH(1-34) amide and the interactions between EGF and PTH-rP(1-34), PTH-rP(1-86) and PTH(1-34), on the proliferation of JAR human choriocarcinoma cells were investigated. Inhibition of PTH-rP(1-34) and PTH-rP(1-86) stimulated cell proliferation by PTH-rP(7-34) and PTH(1-34) were also demonstrated. The effect of dexamethasone with PTH-rP(1-34) on JAR, SaOS-2 and MCF-7 cells was also studied, as well as the effect of cAMP on JAR, F9 and SaOS-2 cell proliferation.
EGF, PTH-rP(1-34) and PTH-rP(1-86) increased proliferation in JAR cells but PTH(1-34) did not. PTH-rP potentiated EGF stimulated cell proliferation in JAR, while there was no effect with PTH(1-34). Dexamethasone inhibited PTH-rP(1-34) stimulated cell proliferation in JAR, SaOS-2 and MCF-7. PTH(1-34) and cAMP increased cell proliferation in SaOS-2. PTH(1-34) had no effect on JAR cell proliferation, while cAMP significantly inhibited JAR cell proliferation. This suggests that alternative types of receptor for PTH-rP(1-34) and PTH-rP(1-86) exist in JAR/trophoblast cells. PTH-rP increased EGF-R expression while PTH(1-34), decreased EGF-R expression in JAR cells. Finally, EGF increased the secretion of PTH-rP by JAR cells.
Thus this thesis has demonstrated that PTH-rP, EGF and glucocorticoids interact in the control of proliferation in JAR cells and trophoblast. The PTH-rP receptor that exists in JAR/trophoblast may not be the same as the classical type I that exist in SaOS-2 cells. PTH-rP which has an autocrine/paracrine action and may be produced by the aggressive invasive 5-7 day implanted trophoblast. This may occur long before the fetal parathyroid starts to secrete PTH-rP, i.e. about 7-8 weeks after implantation. EGF secreted by the maternal endometrium may influence the production of PTH-rP. An understanding of differences in receptor types in the tissues should enable one to develop selective agonist or antagonist. It is possible that these could be used as anti-cancer drugs, or to develop new forms of contraception or fertility assistance.
University of Southampton
Umar, Ali Abdul-Aziz Dikko
0c004853-7009-4a19-87c9-e279f262b7f5
1997
Umar, Ali Abdul-Aziz Dikko
0c004853-7009-4a19-87c9-e279f262b7f5
Umar, Ali Abdul-Aziz Dikko
(1997)
The role of parathyroid hormone-related peptide (PTH-rP) in the regulation of proliferation in trophoblast using choriocarcinoma JAR as a model.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
The effects of EGF, PTH-rP amide and PTH(1-34) amide and the interactions between EGF and PTH-rP(1-34), PTH-rP(1-86) and PTH(1-34), on the proliferation of JAR human choriocarcinoma cells were investigated. Inhibition of PTH-rP(1-34) and PTH-rP(1-86) stimulated cell proliferation by PTH-rP(7-34) and PTH(1-34) were also demonstrated. The effect of dexamethasone with PTH-rP(1-34) on JAR, SaOS-2 and MCF-7 cells was also studied, as well as the effect of cAMP on JAR, F9 and SaOS-2 cell proliferation.
EGF, PTH-rP(1-34) and PTH-rP(1-86) increased proliferation in JAR cells but PTH(1-34) did not. PTH-rP potentiated EGF stimulated cell proliferation in JAR, while there was no effect with PTH(1-34). Dexamethasone inhibited PTH-rP(1-34) stimulated cell proliferation in JAR, SaOS-2 and MCF-7. PTH(1-34) and cAMP increased cell proliferation in SaOS-2. PTH(1-34) had no effect on JAR cell proliferation, while cAMP significantly inhibited JAR cell proliferation. This suggests that alternative types of receptor for PTH-rP(1-34) and PTH-rP(1-86) exist in JAR/trophoblast cells. PTH-rP increased EGF-R expression while PTH(1-34), decreased EGF-R expression in JAR cells. Finally, EGF increased the secretion of PTH-rP by JAR cells.
Thus this thesis has demonstrated that PTH-rP, EGF and glucocorticoids interact in the control of proliferation in JAR cells and trophoblast. The PTH-rP receptor that exists in JAR/trophoblast may not be the same as the classical type I that exist in SaOS-2 cells. PTH-rP which has an autocrine/paracrine action and may be produced by the aggressive invasive 5-7 day implanted trophoblast. This may occur long before the fetal parathyroid starts to secrete PTH-rP, i.e. about 7-8 weeks after implantation. EGF secreted by the maternal endometrium may influence the production of PTH-rP. An understanding of differences in receptor types in the tissues should enable one to develop selective agonist or antagonist. It is possible that these could be used as anti-cancer drugs, or to develop new forms of contraception or fertility assistance.
This record has no associated files available for download.
More information
Published date: 1997
Identifiers
Local EPrints ID: 463158
URI: http://eprints.soton.ac.uk/id/eprint/463158
PURE UUID: ca254f1c-5fc1-4543-b36d-3fce4c255000
Catalogue record
Date deposited: 04 Jul 2022 20:46
Last modified: 23 Jul 2022 01:09
Export record
Contributors
Author:
Ali Abdul-Aziz Dikko Umar
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics