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Claire V Hutchinson, James A Walker and Colin Davidson

Introduction Emerging evidence suggests that appropriate levels of the sex steroid hormone oestrogen (and in particular oestradiol (E 2 )) may be a significant factor in the maintenance of healthy visual function, particularly in older females. To

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O Sukocheva and C Wadham

this review, we analysed recent knowledge gained at the crossroads of sphingolipid and oestrogen signalling pathways in breast cancer cells (BCC). Sphingolipid signalling in a spotlight of anti-cancer research Apoptosis (programmed cell death) is the

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Shuhang Xu, Guofang Chen, Wen Peng, Kostja Renko and Michael Derwahl

diseases in females, several experimental studies have provided evidence that oestrogen is involved in the pathogenesis of thyroid nodules and tumours. Benign and malignant thyroid cells and tissues express functional oestrogen receptors (ERs) and their

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Folley and his colleagues [Folley, Scott-Watson & Bottomley, 1940, 1941] have recently shown that copious lactation may be produced in virgin heifers by the administration of diethylstilboestrol. If this discovery is to be used in veterinary practice, it is obviously important to determine whether the milk so produced contains diethylstilboestrol, and if it does, whether the quantities present are liable to have any action on the people drinking the milk. We have not been able to find any reference in the literature to the excretion of oestrogen in normal milk.

The present report is unfortunately incomplete owing to the departure of one of us (S. W. S.) from this Institute. The preliminary results we have obtained, however, do indicate that small amounts of oestrogen are present in the milk and that it is possible to extract this oestrogen and assay it. None of our results has suggested that the amounts

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A very large number of compounds is now known which reproduce or imitate the action of the naturally occurring oestrogens. The outstanding researches of Dodds and his co-workers have shown that, while potencies equalling or approaching those of the natural substances seem to be possessed only by those synthetic compounds which appear to be closely related to them in structural configuration, the structure of other more weakly oestrogenic compounds may diverge considerably from this type.

Stroud [1940] has shown, however, that when diphenyl, diphenyl ether, diphenylmethane, stilbene and γ:δ-diphenyl-β:δ-hexadiene are injected into female rabbits, phenolic metabolic products are excreted, which are usually more active oestrogenically than the parent compounds. It might be supposed, therefore, that the activity shown by the non-phenolic precursors is due to the formation of the phenols in vivo. The question thus arises, which of the apparently active substances so far described are direct oestrogens, and

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Biological inactivation and metabolism of oestrogens in the normal liver of animals

Biological inactivation and metabolism of oestrogens in the damaged liver of animals

Biological inactivation and metabolism of oestrogens in the normal human liver

The role of conjugation of oestrogens in their biological inactivation

Role of the enterohepatic circulation in the biological inactivation and metabolism of oestrogens in human subjects

Oestrogen metabolism in human subjects with liver disease

Studies in vitro

Studies on urinary excretion of oestrogens using biological and chemical methods

Studies on the biological effects of oestrogens on the vaginal smear and urinary sediment in liver disease

Studies on the mechanism leading to increased oestrogen excretion and to symptoms of increased oestrogen activity in the organism

The relation of the disturbed metabolism of oestrogens to the clinical symptoms seen in liver disease




The nature of the changes in oestrogen metabolism in liver

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Clement K M Ho, Jyoti Nanda, Karen E Chapman and Fouad K Habib

manifests at a stage in life when androgen levels are declining ( Gray et al . 1991 , Harman et al . 2001 ). With advancing age, plasma androgen levels decrease gradually while oestrogen levels remain constant or decrease slightly, resulting in increasing

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It has been shown previously (Jellinck & Lucieer, 1965) that liver microsomes derived from male rats convert a higher proportion of [14C]oestradiol to its 2-hydroxy derivative and to water-soluble products than similar preparations from female rats. This sex difference in oestrogen metabolism could be altered by changing the hormonal environment; male rats acquired a female metabolic pattern when implanted with a pellet of oestrone (Jellinck & Woo, 1967). A number of natural and synthetic oestrogens in pellet form were therefore tested to determine whether they had the same action as oestrone on rat liver microsomes. The effect of structurally related non-oestrogenic analogues was also examined.

Compounds to be tested were compressed into cylindrical pellets (15–25 mg.) and implanted into adult male hooded or Sprague-Dawley rats. The dose released from the pellets is very small (e.g. < 50 μg. oestrone or stilboestrol/day, Jellinck & Woo, 1967). The animals were killed

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Evidence that the liver destroys the activity of oestrogens has been strongly presented in a long list of publications and there appears to be no serious dissenting opinion [Cantarow, Rakoff, Paschkis, Hansen & Walkling, 1943]. The inactivation of oestrogens by isolated liver tissue is one of the clearest demonstrations of this hepatic function [Silberstein, Engel & Molnar, 1933; Heller, 1940; Engel, 1941]. It should also be recalled that Golden & Sevringhaus [1938] implanted ovaries in the mesenteries of rats without producing oestrus; that Biskind [1941] failed to obtain atrophy of the reproductive organs of male rats when pellets of oestrone were implanted into the spleen but that atrophy resulted when the implants were made subcutaneously; and that damage to the liver favours higher concentrations of oestrogens in blood [Talbot, 1939; Pincus & Martin, 1940] and in urine [Glass, Edmondson & Soil, 1940]. Cantarow, Rakoff, Paschkis & Hansen [1942] gave evidence

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It has recently been shown [Emmens, 1941, 1942] that oestrogens may be divided into two classes—those which act directly or with changes that can be effected locally, and for which it is suggested the title oestrogen be retained, and those which apparently need to pass into the general circulation before exhibiting oestrogenic properties, the pro-oestrogens. Oestrogen will, in this communication, refer to the former class.

Two methods are so far available for distinguishing oestrogens from pro-oestrogens. By the first method [Emmens, 1941], the systemic-local ratio (S/L ratio) is determined. This is the ratio between the median effective dose needed in an Allen-Doisy test with spayed mice, when the substance is given subcutaneously in oil, and the median effective dose needed by direct application in 50% water-glycerol to the vaginal canal. For oestrogens the ratio is 50 or more; for pro-oestrogens it approximates to unity. The second method involves the use