Biology of female sex hormone action in relation to contraceptive agents and neoplasia

King, R. J. B.

doi:10.1016/0010-7824(91)90002-w

Cited by 24 publications

(10 citation statements)

References 40 publications

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“…• intrinsic activity of CS in different target organs in different species [21,27,66,77], and • a possible discrimination between the genotoxic and mitogenic effects of substances tested for carcinogenic activity [101].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, CS use has been found to be related to increased proliferative activity of breast epithelium [93,95], and this effect may be more pronounced in young than in old age [95]. Thus it appears that proliferation of mammary epithelium in vivo is stimulated by progesterone, not only in :rodents [76,96,97] and the dog [2,11 ], but also in the human [90][91][92][93], the effect of which may be enhanced by earlier or simultaneous exposure to estrogens [11,76,77,96,97]. Part of this mitogenic effect of progesterone may be the result of effects induced in the stroma [76,96,97].…”

Section: Possible Mechanisms Of Tumor Enhancement By Sex Steroidsmentioning

confidence: 96%

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Contraceptive steroids and the mammary gland: Is there a hazard?

1992

Breast Cancer Res Tr

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The safety of synthetic steroid hormones to be used for contraception in the human female is tested in rats, beagle dogs, and (once marketing starts) in monkeys. Because early studies did not show a mammary tumor stimulating effect in the human, in contrast to findings in the dog, many objections have been raised to the use of the dog for these toxicity studies. It has been claimed that the dog is unique in its sensitivity to the mammary tumor promoting effect of progestins and that this tumorigenic effect results from progestin-induced growth hormone (GH) induction. A thorough review of the literature does not support these claims. Tumor stimulatory effects of progesterone or synthetic progestins can be observed under some conditions in rodents as well as in cats and monkeys. In addition, recent evidence suggests a role for progesterone in mammary tumorigenesis in the human, and contraceptive steroids may also not be completely without risk. While the suggested role for GH in dog mammary tumorigenesis is far from proven, such a role cannot be excluded in the other species. Whether tumor stimulatory effects of sex steroids are based upon induction of proliferation in target cells or upon genotoxic effects or both is not yet certain.

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Section: Discussionmentioning

confidence: 99%

Section: Possible Mechanisms Of Tumor Enhancement By Sex Steroidsmentioning

confidence: 96%

Contraceptive steroids and the mammary gland: Is there a hazard?

1992

Breast Cancer Res Tr

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“…The role of progestins in the pathogenesis of human breast cancer has been highly debated (1)(2)(3)(4). Although there is convincing evidence that ovarian hormones play a prominent role at all stages of mammary development, epidemiologic studies in general do not support an overall increased risk of breast cancer after progestin treatment.…”

Section: Introductionmentioning

confidence: 99%

Growth hormone mRNA in mammary gland tumors of dogs and cats.

Mol¹,

Garderen²,

Pj³

et al. 1995

J. Clin. Invest.

112

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We have shown recently that in the dog progestin administration results in mammary production of immunoreactive growth hormone (GH). At present we demonstrate the expression of the gene encoding GH in the mammary gland of dogs and cats using reverse-transcriptase PCR.GH mRNA was found in the great majority of normal mammary tissues as well as benign and malignant mammary tumors of the dog and was associated with the presence of immunoreactive GH in cryostat sections. The mammary PCR product proved to be identical to that of the pituitary. The highest expression levels were found after prolonged treatment with progestins. In carcinomas GH mRNA was also found in progesterone receptor-negative tissue samples, indicating that after malignant transformation GH gene expression may become progestin independent. GH mRNA was also present in mammary tissues of cats with progestin-induced fibroadenomatous changes.It is concluded that GH gene expression occurs in normal, hyperplastic, and neoplastic mammary tissue of the dog. The expression in normal tissue is stimulated by progestins and might mediate the progestin-stimulated development of canine mammary tumors. The demonstration of progestin-stimulated GH expression in mammary tissue of cats indicates that the phenomenon is more generalized among mammals. (J. Clin. Invest. 1995.95

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“…Néan-moins, notamment dans la population à haut risque, les séries sont décevantes avec à la fois de nombreux faux positifs (interventions chirurgicales inutiles) et des tumeurs de stade très évolué apparaissant entre deux examens [28]. Le nombre de faux positifs apparaît très important : 324 interventions pour 22 tumeurs et 180 interventions pour 17 cancers [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. L'objectif est donc de diminuer le nombre de faux positifs.…”

Section: Dépistage Les Grands Défisunclassified