Some Aspects of the Biochemistry of Oestrogens

Abstract

The thesis is concerned with several aspects of oestrogen biochemistry. It has two main divisions. In the first part, a review of the clinical and physiological role of oestrogens is given, together with a discussion of the use to-which oestrogen determinations are put in the management of pregnancy. The methods currently available for the determination of oestrogens in body fluids are reviewed and criticised. The available methods are found to be inadequate for a variety of reasons, and a new assay for oestrogens in pregnancy urine is described which overcomes these difficulties. This assay is based on the native fluorescence of the oestrogens, and the theoretical and practical basis for this method of assay is presented and discussed. A certain amount of clinical evidence is given to support the suggestion that this test is better suited to the hospital environment than any previously published method. The second part of the thesis concerns the effects which the oestrogen molecule may have on the cell membranes of the tissues with which it comes into contact. The numerous effects which oestrogens appear to have on tissues which are not considered to be target tissues suggest that there is more than one mode of action for the oestrogen response. This problem is investigated in the highly responsive cell type, the thymic lymphocyte, where oestrogen is found to interfere with the calcium mediated responses consonant with stimulation by mitogens or hormones. The method is also shown to be applicable to study of the highly specialised cell remnant, the blood platelet. A mechanism is proposed whereby oestrogen may interfere with the hormonal response of cells within the body, and the relationship between this effect and the roles of ions and cyclic nucleotides within the cell is discussed. These propositions are based on the data obtained with the use of a new series of fluorescent dyes which are used as probes for membrane characteristics such as the trans-membrane potential. Experimental detail is given where appropriate, and the techniques used-are described in detail. The conclusion of the thesis is that oestrogens may affect cells which have hitherto not been considered to be particularly responsive to the hormone, and that this effect of oestrogens may well lie in the ability of the hormone to interfere with ion movements across, and within, the plasma membrane. It may prove to be that the same structural characteristic of the oestrogen molecule which allows for a fluorescent determination of the hormone also permits the intervention of the hormone in the processes of cells other than classical oestrogen target cells.