| dc.contributor.advisor | The aim of the studies described in this thesis was to investigate
whether
1. LHRH (luteinizing-hormone-releasing hormone) modulates hCG release
from the syncytiotrophoblast through the mediation of specific
receptors and
2. chronic exposure to native LHRH or its more potent agonist
(D-ser-t-bu(6) des-Gly-NH(2)(10)) LHRH ethylamide leads to a
reduction in hCG output. | en |
| dc.contributor.advisor | To examine tissue for the presence of specific LHRH receptors
l,000g, 10,000g and 100,000g preparations of placental tissue from both
term and 8-12 weeks gestation were incubated with mono-iodinated LHRH
agonist and increasing concentrations of cold LHRH agonist. Specific
binding sites were shown to be present (Ka=5x10^M(-1) both on
normal tissue and on hydatidiform mole. LHRH had the same affinity for
the receptors in these tissues as the agonist. | en |
| dc.contributor.advisor | To determine whether the low affinity of the receptor was due to
degradation of the ligands, binding studies were carried out in the
presence of enzyme inhibitors. Contrary to expectation the inhibitors
decreased binding but did not increase the affinity. It appeared that
thiol and serine inhibitors blocked binding while carboxyl inhibitors
showed no effect. An enzyme substrate L-leucine β-naphthylamine
inhibited binding but when leucine and naphthylamine were examined,
naphthylamine alone reduced binding. | en |
| dc.contributor.advisor | Degradation of native and agonist LHRH were compared and, as in
other tissues, the agonist was more resistant to degradation than
native LHRH. | en |
| dc.contributor.advisor | The effect of LHRH and the agonist on hCG production by cultures
of explants of 12 week trophoblastic tissue was studied during 5 days
of culture. No consistent stimulation of hCG secretion could be
demonstrated. Culture of term placental villi for 5 days showed no
overall synthesis of hCG and daily hCG secretion declined in a similar
manner to that shown by Siler-Khodr & Khodr (1979). Electron
microscopic studies of the term placental villi showed considerable
changes in morphology during culture. After only 1 day in culture the
nuclei were densely stained and the microvilli were no longer present
and while after 2 days the syncytium was becoming detached from the
basement membrane. During the following days of culture there was
further deterioration of the tissue. | en |
| dc.contributor.advisor | To overcome the problem of tissue viability a second method of
culture was adopted. Minced chorionic villi or collagenase dispersed
cells were supported in Biogel columns and perfused with medium.
Hormones released in response to LHRH and its agonist were measured in
fractions collected every five minutes. With minced tissue LHRH
released more peaks of hCG than did the control (x(2):p<0.05). However
80% of pulses resulted in no significant increase in hCG release. | en |
| dc.contributor.advisor | The results suggested that although the presence of both LHRH-like
factors and specific LHRH receptors in the placenta have been reported,
LHRH does not appear to play a major role in the regulation of hCG
production by the placenta. | en |
| dc.contributor.author | Currie, Aileen Jane | en |
| dc.date.accessioned | 2018-01-31T11:19:37Z | |
| dc.date.available | 2018-01-31T11:19:37Z | |
| dc.date.issued | 1983 | |
| dc.identifier.uri | http://hdl.handle.net/1842/26423 | |
| dc.description.abstract | | en |
| dc.publisher | The University of Edinburgh | en |
| dc.relation.ispartof | Annexe Thesis Digitisation Project 2017 Block 15 | en |
| dc.relation.isreferencedby | Already catalogued | en |
| dc.title | Investigations into the role of LHRH in the regulation of hCG release by the human placenta | en |
| dc.type | Thesis or Dissertation | en |
| dc.type.qualificationlevel | Doctoral | en |
| dc.type.qualificationname | PhD Doctor of Philosophy | en |
