Further Studies of the Metabolism of Oestradiol in Man

Fishman, Jack; Bradlow, H. Leon; Zumoff, Barnett; Hellman, Louis M.; Tf, Gallagher

doi:10.1530/acta.0.0370057

Cited by 17 publications

(6 citation statements)

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“…The tritium contained in the body water following estradiol-17 -3H administration is also given in Table II. In this case the body water volume was calculated from the lean body mass formula (Miller and Blyth, 1952) to give a body water tritium content in accord with previous results showing a rapid and essentially complete oxidation of estradiol to estrone (Fishman et al, 1961).…”

Section: Resultsmentioning

confidence: 96%

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Aromatic ring hydroxylation of estradiol in man

Fishman¹,

Guzik²,

Hellman³

1970

Biochemistry

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Section: Resultsmentioning

confidence: 96%

“…17/3-Estradiol-4-14C (31.8 mCi/mmole) was obtained commercially. 17/3-Estradiol-17 -(63 pCi/mg) was prepared in this laboratory as previously described (Fishman et al, 1961). Both labeled substrates were better than 97 % pure by reverse isotope dilution.…”

Section: Materials and Methods1mentioning

confidence: 99%

Aromatic ring hydroxylation of estradiol in man

Fishman¹,

Guzik²,

Hellman³

1970

Biochemistry

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“…Since age per se does not affect these transformations, we can presume that the breast cancer patients possessed an increased extent of this reaction prior to the onset of the MATERIALS AND METHODS The radiometric method of measuring estrogen metabolism in vivo involves the use of estradiol substrates labeled with 3H at stereospecific sites from which the isotope is transferred into the body water pool upon metabolism at that site. Specifically labeled estradiols were prepared as previously described (7)(8)(9) The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C.…”

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confidence: 99%

Estradiol 16 alpha-hydroxylation in the mouse correlates with mammary tumor incidence and presence of murine mammary tumor virus: a possible model for the hormonal etiology of breast cancer in humans.

Bradlow¹,

Hershcopf²,

Martucci³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

180

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In this report, we describe our findings on the relationship between estradiol 16a-hydroxylation and mammary tumor incidence. A close correlation between the two has been demonstrated with 16-hydroxylation being elevated in strains with a high incidence of tumors, such as RIII and C3H, and low in strains with a low incidence of cancer, such as C57BL. The extent of reaction is highly reproducible and unaffected by age or presence of overt mammary tumors. Studies on the inheritance of estradiol 16a-hydroxylase showed that it is inherited as an autosomal dominant and is not correlated with estradiol 2-hydroxylase or androgen and progestin 16a-hydroxylases. In addition, the reaction was shown to be markedly enhanced by the presence of murine mammary tumor virus and diminished in the absence of the virus. These studies establish a relationship between genetics, hormonal factors, and murine mammary tumor virus, the three key factors in mammary tumorigenesis. disease, unless the increase was a consequence of the cancer itself. An animal model with spontaneous estrogen-mediated mammary tumors in which the extent of estrogen 16a-hydroxylation could be readily studied before and after tumor development would assist in choosing between the alternative hypotheses offered above. In addition, such a model would facilitate studies on the mechanisms by which this reaction is regulated and whether it affects the initiation or promotion of the disease. In this report, we describe our studies on estrogen metabolism in the murine mammary tumor model, which show that a close relationship between the extent of tumor incidence and 16a-hydroxylation of estradiol exists. Furthermore, we find that the presence of exogenous mouse mammary tumor virus (MMTV) increases 16a-hydroxylation of estradiol, providing a possible link between the viral and hormonal elements of mammary tumorigenesis in the mouse.Epidemiological evidence dating back to the observations of Beatson (1) provides a strong argument that endogenous estrogens participate in the etiology and progress of human breast cancer (2). Because of this, much effort has been directed to the identification of differences in the secretion and/or metabolism of estrogens in women with breast cancer, but the results obtained have been contradictory and the existence of such differences remains equivocal (3). A possible reason for this failure to discern a consistent difference is that breast cancer is a disease with a long latent period (4) and, consequently, the hormonal status at the time of diagnosis may not reflect that existing at the time of disease initiation. Clearly, secretion of estrogens is highly dependent on age and menopausal status and we have therefore sought to find a measure of estrogen metabolism that is not affected by age or menopausal stage and that will reflect metabolic status at the time of disease initiation. Using a radiometric procedure for measuring the enzymatic activity of the major pathways of the oxidative metabolism of estradiol, 17,3-ol oxidation, a...

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“…Release of tritium into body water following oxidation at C-21 is an indirect process in which tritium is initially incorporated into NADT or NADPT. This labeled cofactor may either be used to reduce other 3.8 5.7 molecules as described by Fishman et al (9) and Wengel (10) or to enter a rapid oxidative chain in which the tritium finally ends as water. In the exchange process the tritium on the steroid is directly exchanged for protium via an enzyme mediated exchange.…”

Section: Resultsmentioning

confidence: 99%

Studies in the Biotransformation of Cortisol to Cortoic Acids in Man. III. 21-Oxidation of 4-¹⁴C,21-³H-Desoxycorticosterone

Bradlow

Monder

Zumoff

1977

The Journal of Clinical Endocrinology & Metabolism

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The metabolism of (4-14C, 21-3H) desoxycorticosterone (DOC) in man has been studied. DOC, like cortisol, undergoes oxidation at C-21 with the formation of acidic metabolites (2.3-8.2% of the dose). The release of 3H into the body water, either by oxidation or exchange, is approximately twice as great as the actual formation of acidic metabolites (as judged from the recovery of 14C in the urinary acidic fraction), but both parameters were considerably smaller than the corresponding values for cortisol. The principal metabolite isolated from the urine was 21-hydroxypregnanolone, which had an isotope ratio (3H/14C) greater than that of the dose; the pregnanetriols, which were formed in lesser amounts, had significantly lower isotope ratios than the dose. The absence of the 17-hydroxy group in DOC appears to modify C-21 oxidation, decreasing its magnitude and altering the character of the products.

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Further Studies of the Metabolism of Oestradiol in Man

Cited by 17 publications

References 0 publications

Aromatic ring hydroxylation of estradiol in man

Aromatic ring hydroxylation of estradiol in man

Estradiol 16 alpha-hydroxylation in the mouse correlates with mammary tumor incidence and presence of murine mammary tumor virus: a possible model for the hormonal etiology of breast cancer in humans.

Studies in the Biotransformation of Cortisol to Cortoic Acids in Man. III. 21-Oxidation of 4-¹⁴C,21-³H-Desoxycorticosterone

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Further Studies of the Metabolism of Oestradiol in Man

Cited by 17 publications

References 0 publications

Aromatic ring hydroxylation of estradiol in man

Aromatic ring hydroxylation of estradiol in man

Estradiol 16 alpha-hydroxylation in the mouse correlates with mammary tumor incidence and presence of murine mammary tumor virus: a possible model for the hormonal etiology of breast cancer in humans.

Studies in the Biotransformation of Cortisol to Cortoic Acids in Man. III. 21-Oxidation of 4-14C,21-3H-Desoxycorticosterone

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Studies in the Biotransformation of Cortisol to Cortoic Acids in Man. III. 21-Oxidation of 4-¹⁴C,21-³H-Desoxycorticosterone