Inhibitory effect of androgens on DMBA-induced mammary carcinoma in the rat

Dauvois, Sophie; Li, Shengmin; Martel, Céline; Labrie, Fernand

doi:10.1007/bf01806301

Cited by 46 publications

(15 citation statements)

References 42 publications

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“…To investigate the possibility that DHEA and its metabolites could have a preventive effect on the development of mammary carcinoma, we have studied the effect of increasing circulating levels of DHEA constantly released from Silastic brand implants on the development of mammary carcinoma induced by DMBA in the rat. The DMBA-induced mammary carcinoma in the rat has been widely used as a model of hormone-sensitive breast cancer in women (242,256,257).…”

Section: Inhibitory Effect Of Dhea On Breast Cancermentioning

confidence: 99%

Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone

et al. 2003

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Serum androgens as well as their precursors and metabolites decrease from the age of 30-40 yr in women, thus suggesting that a more physiological hormone replacement therapy at menopause should contain an androgenic compound. It is important to consider, however, that most of the androgens in women, especially after menopause, are synthesized in peripheral intracrine tissues from the inactive precursors dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S) of adrenal origin. Much progress in this new area of endocrine physiology called intracrinology has followed the cloning and characterization of most of the enzymes responsible for the transformation of DHEA and DHEA-S into androgens and estrogens in peripheral target tissues, where the locally produced sex steroids are exerting their action in the same cells in which their synthesis takes place without significant diffusion into the circulation, thus seriously limiting the interpretation of serum levels of active sex steroids. The sex steroids made in peripheral tissues are then inactivated locally into more water-soluble compounds that diffuse into the general circulation where they can be measured. In a series of animal models, androgens and DHEA have been found to inhibit breast cancer development and growth and to stimulate bone formation. In clinical studies, DHEA has been found to increase bone mineral density and to stimulate vaginal maturation without affecting the endometrium, while improving well-being and libido with no significant side effects. The advantage of DHEA over other androgenic compounds is that DHEA, at physiological doses, is converted into androgens and/or estrogens only in the specific intracrine target tissues that possess the appropriate physiological enzymatic machinery, thus limiting the action of the sex steroids to those tissues possessing the tissue-specific profile of expression of the genes responsible for their formation, while leaving the other tissues unaffected and thus minimizing the potential side effects observed with androgens or estrogens administered systemically.

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Section: Inhibitory Effect Of Dhea On Breast Cancermentioning

confidence: 99%

Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone

et al. 2003

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“…Treatment with testosterone alone also induced mammary tumors in the same rat strain (7,8). In contrast, inhibitory effects of androgens on the development (9) or progression (10) of dimethylbenz(a)anthracene-induced mammary tumors in female rats have been reported. Occasional enhancement of tumor growth was observed in some experiments in which moderate or very high doses of androgen were used (reviewed in Ref.…”

Section: Introductionmentioning

confidence: 90%

Morphological changes induced by testosterone in the mammary glands of female Wistar rats

Chambô-Filho

Camargos

Pereira

2005

Braz J Med Biol Res

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Increased levels of androgens in postmenopausal women are considered to be a risk factor for breast cancer. Testosterone, alone or in combination with estrogen, induces epithelial dysplasia and mammary tumors in Noble rats. Since this model of hormone-induced neoplasia has not been reported in other rat strains, we studied the effect of testosterone on the mammary gland morphology of female Wistar rats. Sixty adult, non-castrated, female Wistar rats were implanted in the dorsum midline with a silicone tube containing 50 mg testosterone (testosterone propionate in 30 animals and non-esterified testosterone in the remaining 30 animals) and 20 additional animals were implanted with empty tubes and used as control. Five animals per group were killed 30, 60, 90, 120, 150, and 180 days after implantation, and the mammary glands were dissected, fixed and embedded in paraffin. Histological sections were then stained with hematoxylin and eosin and picrosyrius red for collagen visualization. Morphological and morphometric analysis demonstrated ductal proliferation and acinotubular differentiation with secretory activity in all treated animals, peaking at 90 days of androgen exposure. After 90 days the proliferation of acinar epithelial cells was evident, but there was a progressive reduction of secretory differentiation and an increase in intralobular collagen fibers. There was no morphological evidence of dysplastic changes or other pre-neoplastic lesions. Testosterone treatment applied to adult, non-castrated female Wistar rats induced a mammary gland hyperplasia resembling the lactating differentiation, with progressive reduction in secretory differentiation. Correspondence

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“…The two largest perpendicular diameters of each tumor were measured with calipers and the product of these diameters was used to estimate tumor size [17]. Tumor size measured on the day of OVX or on the day before starting treatment was taken as 100%.…”

Section: Treatmentmentioning

confidence: 99%

“…[17] have shown that constant release of the androgen DHT in ovariectomized rats bearing DMBA-induced mammary carcinoma caused a marked inhibition of tumor growth induced by 17[~-estradiol (E2). That DHT acts through interaction with the androgen receptor is supported by the finding that simultaneous treatment with the antiandrogen Flutamide completely prevented DHT action.…”

Section: Growth Inhibition Of Rat Mammary Tumorsmentioning

confidence: 99%

Growth inhibition of 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors by controlled-release low-dose medroxyprogesterone acetate

Lepage

Mérand

et al. 1992

Breast Cancer Res Tr

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Since our previous findings had indicated that the androgenic steroid medroxyprogesterone acetate (MPA) exerts potent inhibitory effects on 7,12-dimethylbenz(a)anthracene (DMBA)-induced tumor growth, we have studied the effect of low doses of MPA released from Depo-Provera and from 50:50 poly[DL-lactide-co-glycolide] microspheres in the same DMBA-induced tumor model. The present data show that single subcutaneous injection of a 4-month controlled-release formulation of biodegradable 50:50 poly[DL-lactide-co-glycolide] microspheres containing 10 mg of MPA giving serum levels of 3.14 +/- 0.32 ng/ml (8.12 +/- 0.83 nM) MPA causes a maximal or near-maximal 60% inhibition of tumor growth measured 56 days later. Such data suggest that controlled-release formulations giving constant and low blood levels of MPA could be used for the treatment of breast cancer in women. Such a low concentration of MPA should avoid the side effects observed with the high doses of the compound.

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Inhibitory effect of androgens on DMBA-induced mammary carcinoma in the rat

Cited by 46 publications

References 42 publications

Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone

Endocrine and Intracrine Sources of Androgens in Women: Inhibition of Breast Cancer and Other Roles of Androgens and Their Precursor Dehydroepiandrosterone

Morphological changes induced by testosterone in the mammary glands of female Wistar rats

Growth inhibition of 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors by controlled-release low-dose medroxyprogesterone acetate

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