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Title: Metabolism of the oestrogens and their conjugates
Author: Hobkirk, Ronald
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1973
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Optimal conditions for hydrolysis of urinary oestrogen conjugates in the human have been sought, A β-glucuronidasesulphatase mixture (H, plmatia) is shown to be effective in cleaving the sulphate and glucosiduronate forms of some eight metabolites, A bacterial (E, coli) β-glucuronidase preparation is particularly active in hydrolysing both oestrogen and 17-ketosteroid glucosiduronates. Using these techniques and other improved methodology, levels of seven or eight oestrogen metabolites have been measured in normal and diabetic pregnancy (human). Apparent abnormalities are seen in the diabetic state and tentative conclusions are drawn regarding sites of production of certain oestrogens during pregnancy. Metabolism of some free oestrogens have been studied in the human in vivo and in vitro and in certain other species in vitro. Oestriol and 16-epioestriol are shown to be not necessarily 'end products' of metabolism but to be variably metabolized by laying hen liver, erythrocytes of certain species and by the human in vivo. The 2-methoxylation of oestrone has been studied in rat liver fractions and the metabolism of the clinically useful synthetic compound 17α-ethynyloestradiol-17β-3-cyclopentyl ether has been delineated in the human. The conjugation patterns of urinary oestrogen metabolites in the pregnant and non-pregnant human are shown to be similar by a differential hydrolytic technique. The quantitative importance of oestrone in the sulphate fraction has been established as well as that of 16?-hydroxyoestrone and 16-ketooestradiol-17β in the sulphoglucosiduronate fraction. It has been shown that tissues from the laying hen are more active, with respect to aulphurylation, towards phenolic steroids than to dehydroisoandrostarone. Also, liver from the same species directly interconverts the 3~sulphates of oestrone and 17β-oestradiol. The ability of a rat liver preparation to sulphurylate the 3 position of phenolic steroids appears to be related to the constituents of ring D of the steroid. The glucosiduronates and sulphates of oestrone and 17β-oestradiol have been successfully separated chromatographically and the procedure has been employed to prove that the human conjugates 17β-oestradiol to yield both its 3- and 17-monoglucosiduronates. The fates of the latter two conjugates differ in vivo in that the former is subjected mainly to 17-dehydrogenation and little deconjugation, whereas the latter undergoes an enterohepatic type of metabolism with considerable deconjugation and reconjugation. The metabolism of the monoglucosides of 17β-oestradiol in the human has been studied. The 3-glucoside residue is rapidly removed with the release, and extensive metabolism, of 17?-oestradiol. The 17-glucoside residua is much less readily removed and the metabolism of the 17-glucosides of 17?-oestradiol and 17α-oestradiol shows some resemblance to that of 17β-oestradiol-17-glucosiduronate.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (D.Sc.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available