Abstract
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 16α-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 17Β-oestradiol. The 17-glucoside residua is much
less readily removed and the metabolism of the 17-glucosides of
17Β-oestradiol and 17α-oestradiol shows some resemblance to that
of 17Β-oestradiol-17-glucosiduronate.
