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Title: The molecular mechanisms of steroid hormone action
Author: Hyder, Salman M.
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1983
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(a) Clinical Aspects The relationship between the molecular forms of oestrogen receptor (4S and 8S forms) in human breast cancer and subsequent response to hormone therapy is controversial. The data presented in this thesis show that several factors can effect the final sucrose density gradient profile of soluble oestrogen receptor under low salt conditions. These include incubation time with steroid, temperature, ionic strength, extent of aggregation and intratumoural variation. It is further shown that buffer made 50% in glycerol can be used to preserve the molecular form of oestrogen receptor in human breast tumour biopsies prior to and subsequent to transportation. Receptor 8S form was preserved for up to 3 months under these conditions. Most tumour biopsies analyzed exhibited the presence of 8S form of the receptor either alone or in conjunction with the 4S form. Relatively few tumours exhibited predominantly the 4S form. Analysis of intratumoural sections revealed a loss of receptor concentration towards the centre of the tumour. The molecular forms found across a tumour usually remained constant. However, when both 8S and 4S forms of receptor were detected, the relative concentration of each form changed across the tumour. These results indicate that strict criteria, with respect to analysis of molecular forms of oestrogen receptor, must be observed if these are to be related to potential response of individual patients to endocrine therapy. (b) Receptor activation/transformation The mechanism of receptor activation/transformation was studied in immature rat uterus, human breast carcinoma and endometrial tissue.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available