Mammary cancer produced in mice with estriol

Rudali, G; Apiou, Françoise; Muel, B.

doi:10.1016/0014-2964(75)90035-3

Cited by 58 publications

(11 citation statements)

References 4 publications

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“…The time at which the half-maximal percentage ofoxidation was reached after the administration of these tracer steroids was calculated for the two groups of subjects ( (1-3, 24). In addition, mammary tumors can be produced in rodents by the administration of exogenous estrogens (25,26). …”

Section: Resultsmentioning

confidence: 99%

Abnormal oxidative metabolism of estradiol in women with breast cancer.

Schneider¹,

Kinne²,

Fracchia³

et al. 1982

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

215

106

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The three dominant oxidative biotransformations of estradiol were examined in 10 normal women and 33 females with breast cancer by using a recently devised radiometric method. Estradiol tracers, labeled with 3H specifically in the 17a, C-2, or 16a position, were used to measure both the rate and extent of 17P-ol oxidation (the initial metabolic step) and the subsequent 2-and 16a-oxidative reactions. The mean ± SEM values for the extent of estradiol metabolism at these three specific sites were 76.9 ± 5.3%, 31.1 ± 4.0%, and 9.3 ± 0.8%, respectively, in normal subjects. Corresponding data in patients with breast cancer-i.e., 73.0 ± 4.2%, 32.7 ± 2.7%, and 14.9 ± 1.5%-revealed a significantly greater extent of 16a-hydroxylation in the latter population. Because the 16a-hydroxylated compounds (including estriol) are themselves potent estrogens, these changes may have important hyperestrogenic consequences that could have a bearing on the etiology of the disease.Endocrine factors have been implicated in the initiation or promotion, or both, of mammary tumorigenesis based on data collected from several sources. These include both experimental studies using animal models and epidemiological and clinical investigations in human subjects (1). Thus, certain features of the menstrual history and age at parity, which can lengthen the period ofexposure to estrogens secreted by the ovaries, appear to be associated with an increased risk for the disease (2, 3). On the other hand, oophorectomy prior to age 35 can lessen the risk of breast cancer (3). Because an augmentation in estrogen secretion could be implicated in the etiology of the human disease, numerous studies have been conducted to detect such an increase in women with, or at high risk to develop, breast cancer (4). Although some investigators have reported significant differences in urinary or plasma estrogen levels, or both, between these subjects and normal individuals (5-7), these findings have not been consistent and have been challenged by others (8, 9). An alternative and possibly more viable hypothesis that an alteration in estrogen metabolism is associated with breast cancer (4, 10) has also been the subject of extensive investigations.The metabolism of estradiol, which is primarily oxidative, consists ofan initial oxidation ofthe 17/3-hydroxy group to yield estrone. This steroid is subsequently metabolized mainly through either of two alternate hydroxylative pathways; namely, hydroxylation at the C-2 or the 16a position (11). These hydroxylations are of particular interest in that they constitute competing reactions whose products are themselves active compounds characterized by markedly different biological properties. The 16a-hydroxyestrogens-estriol and 16a-hydroxyestrone-demonstrate uterotropic activity comparable to that of the parent hormone, estradiol (12, 13). On the other hand, the principal 2-hydroxyestrogens-2-hydroxyestrone and 2-methoxyestrone exhibit virtually no peripheral estrogenic effects but appear to play a regulatory role in neur...

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Section: Resultsmentioning

confidence: 99%

Abnormal oxidative metabolism of estradiol in women with breast cancer.

Schneider¹,

Kinne²,

Fracchia³

et al. 1982

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

215

106

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“…E 2 administration decreased the latency for the development of mammary adenocarcinoma, and increased the incidence of cervical, uterine, vaginal, and bone tumors in mice (Rudali et al 1975, Highman et al 1980, 1981, and increased the incidence of mammary and pituitary tumors in rats (Shull et al 1997). Naturally occurring and synthetic estrogens are kidney carcinogens in castrated male hamsters (Li et al 1983).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, 4-hydroxylation of E 2 was reported to be elevated in human breast tumor biopsies over that of normal breast tissue samples (Liehr & Ricci 1996. Treatment with 16 -OH E 2 caused mammary tumors in mice (Rudali et al 1975) and adrenal, mammary, and pituitary tumors in rats (Noble et al 1975). Urine analyses of premenopausal women showed that a higher ratio of urinary 2-OH E 1 to 16 -OH E 1 was associated with a decreased risk of developing breast cancer after 5 years (Muti et al 2000).…”

Section: Introductionmentioning

confidence: 99%

The effects of steroidal estrogens in ACI rat mammary carcinogenesis: 17β-estradiol, 2-hydroxyestradiol, 4-hydroxyestradiol, 16α-hydroxyestradiol, and 4-hydroxyestrone

Turan¹,

Sánchez²,

Li³

et al. 2004

Journal of Endocrinology

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Several investigators have suggested that certain hydroxylated metabolites of 17 -estradiol (E 2 ) are the proximate carcinogens that induce mammary carcinomas in estrogensensitive rodent models. The studies reported here were designed to examine the carcinogenic potential of different levels of E 2 and the effects of genotoxic metabolites of E 2 in an in vivo model sensitive to E 2 -induced mammary cancer. The potential induction of mammary tumors was determined in female ACI rats subcutaneously implanted with cholesterol pellets containing E 2 (1, 2, or 3 mg), or 2-hydroxyestradiol (2-OH E 2 ), 4-hydroxyestradiol (4-OH E 2 ), 16 -hydroxyestradiol (16 -OH E 2 ), or 4-hydoxyestrone (4-OH E 1 ) (equimolar to 2 mg E 2 ). Treatment with 1, 2, or 3 mg E 2 resulted in the first appearance of a mammary tumor between 12 and 17 weeks, and a 50% incidence of mammary tumors was observed at 36, 19, and 18 weeks respectively. The final cumulative mammary tumor incidence in rats treated with 1, 2, or 3 mg E 2 for 36 weeks was 50%, 73%, and 100% respectively. Treatment of rats with pellets containing 2-OH E 2 , 4-OH E 2 , 16 -OH E 2 , or 4-OH E 1 did not induce any detectable mammary tumors. The serum levels of E 2 in rats treated with a 1 or 3 mg E 2 pellet for 12 weeks was increased 2-to 6-fold above control values (30 pg/ml). Treatment of rats with E 2 enhanced the hepatic microsomal metabolism of E 2 to E 1 , but did not influence the 2-or 4-hydroxylation of E 2 . In summary, we observed a dosedependent induction of mammary tumors in female ACI rats treated continuously with E 2 ; however, under these conditions 2-OH E 2 , 4-OH E 2 , 16 -OH E 2 , and 4-OH E 1 were inactive in inducing mammary tumors.

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“…However, exposition for those estrogens for a long period of time causes, contrary to the prevailing opinion, a stimulating and not suppressive effect. It was proved in a study on mice where neoplastic tumour was induced by both estradiol and estriol as well [15].…”

Section: Menopausal Periodmentioning

confidence: 99%

Physiology and pathology of the mammary gland in women in different periods of life (menopausal period and pregnancy)

Wróbel¹,

Putowski²,

Gogacz³

et al. 2013

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SummaryKnowledge of physiology of the mammary gland help us understand pathological processes which can occur in this organ, for example carcinogenesis. The results of epidemiological studies indicate an increased incidence of breast cancer in women receiving sex steroids, but the data concerning this issue are not unequivocal. The results of WHI (Women Health Initiative) and HERS (Heart and Estrogen/Progestin Replacement Study) studies point out to an elevated risk of neoplasia in the mammary gland among women taking hormone replacement therapy, which evokes a great deal of concern, uncertainty and fear both among doctors and patients. This fear should be replaced by the algorithm of professional medical management and a suitable choice of therapy in relation to a woman's age, genetic load, history of diseases and expected benefits. Directing a therapeutic option to the patient and supporting it with scientific data on HRT can convince women that the treatment will prevent, to a large extent, fractures, depression, Alzheimer's disease, colon cancer, stroke and heart attack. The risk of possible breast cancer death is much lower than compared to the affliction caused by estrogen depletion during early menopause. In the following review we present data which deal with physiology of the mammary gland in different periods of the woman's life, especially menopause. Moreover, the molecular mechanisms that may potentially play a role in neoplasia are discussed.Key words: mammary gland, breast cancer, hormone replacement therapy. StreszczenieZnajomość fizjologii gruczołu piersiowego kobiet pomaga w zrozumieniu mechanizmów odpowiedzialnych za rozwój procesów patologicznych tego gruczołu, w tym raka. Wyniki badań epidemiologicznych wskazują na wzrost częstości występowania raka piersi u kobiet przyjmujących hormony płciowe, ale dane dotyczące tej kwestii nie są jednoznaczne. Wyniki badań WHI (Women Health Initiative) i HERS (Heart and Estrogen/Progestin Replacement Study) zwracają uwagę na podwyższone ryzyko nowotworzenia w gruczole piersiowym w grupie kobiet stosujących hormonalną terapię zastępczą. Wywołuje to wiele niepokoju, niepewności i obaw zarówno wśród lekarzy, jak i pacjentek. Obawy te powinny zostać zastąpione przez profesjonalny algorytm postępowania i odpowiedni dobór terapii w zależności od wieku pacjentki, jej obciążenia genetycznego, chorób współistnieją-cych i spodziewanych korzyści dla układu kostnego, pokarmowego, nerwowego i krążenia. Odpowiednie przedstawienie tej opcji terapeutycznej i podparcie jej danymi naukowymi może przekonać kobiety do hormonalnej terapii zastępczej i wynikających z niej korzyści, takich jak zmniejszenie ryzyka wystąpienia złamania kości udowej, zapobieganie depresji i chorobie Alzheimera, profilaktyka raka jelita grubego, udaru i zawału serca. W niniejszej pracy zaprezentowano przegląd artykułów poruszających kwestię fizjologii gruczołu sutkowego w różnych okresach życia kobiety, poświęcając szczególną uwagę okresowi menopauzy. Ponadto przedstawiono mechanizmy molekularne, kt...

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Mammary cancer produced in mice with estriol

Cited by 58 publications

References 4 publications

Abnormal oxidative metabolism of estradiol in women with breast cancer.

Abnormal oxidative metabolism of estradiol in women with breast cancer.

The effects of steroidal estrogens in ACI rat mammary carcinogenesis: 17β-estradiol, 2-hydroxyestradiol, 4-hydroxyestradiol, 16α-hydroxyestradiol, and 4-hydroxyestrone

Physiology and pathology of the mammary gland in women in different periods of life (menopausal period and pregnancy)

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