Early indicators for carcinogenesis in sex-hormone-sensitive organs

doi:10.1016/0027-5107(91)90067-X

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis

Volume 248, Issue 2, June 1991, Pages 341-356

https://doi.org/10.1016/0027-5107(91)90067-X Get rights and content

Abstract

Hormones induce tumours in various target tissues in different species of laboratory animals in long-term toxicity studies. Examples of such tumours are: mammary gland tumours in beagle dogs after long-term treatment with progestogens or progestogen/oestrogen combinations; pituitary and mammary gland tumours in rats and mice after long-term treatment with oestrogens or progestogens with an oestrogenic partial effect; interstitial cell tumours in rats after chronic overstimulation by endogenous lutenising hormone; endometrial carcinomas in rats after chronic treatment with dopamine agonists.

As a rule every hormone when given in excessive doses over prolonged periods can induce a tumour in the relevant target organs. Drugs or chemicals which stimulate or inhibit the endogenous hormone production of certain endocrine organs can have the same effect.

Tumour induction can be a direct or indirect effect involving specific regulatory mechanisms. In general, the induction is preceded by excessive hyperlasia of the target tissue concerned or with regard to the pituitary where excess production of the stimulating hormone occurs.

Tumour induction in chronic toxicity studies can usually be predicted by determining hormone levels in short-term studies. Hormones and drugs or chemicals which induce tumours when given in doses high enough to induce hyperlasia are unlikely to do so by a genotoxic mechanism.

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Early indicators for carcinogenesis in sex-hormone-sensitive organs

Abstract

Am. J. Obstet. Gynecol.

The regulation of corpus luteum function by hypohyseal luteotrophin

Endocr.

Food and Drug Administration requirements for toxicity testing of contraceptive products

Absence of uterine neoplasia in patients on bromocriptine

Br. Med. J.

Observations sur la structure des ovaires chez des rats soumis à l'influence de la prolactine

Ann. Endocr. (Paris)

Evaluation of effects of sexual steroids on the hypothalamic-pituitary system of animals and man

Arch. Toxicol.

Functional corpora lutea maintained for months by autografts of rat hypophyses

Endocrinology

The extrapolation of experimental findings (animal to man): the dilema of the systematically administered contraceptives

Bull. Soc. Pharmacol. Environ. Pathol.

Contraceptive hormones: the problem of the induction of mammary gland nodules in beagle dogs given progestogens

Bromocriptine and uterine neoplasia

Br. Med. J.

Ergot alkaloids and related compounds

Effect of oestrogen and progesterone on mammary gland DNA and feed intake in hypophysectomized female rats

Influence of an oral contraceptive (ethinyl estradiol/d-norgestrel) on growth hormone and insulin secretion

Schweiz. Med. Wschr.

Neuroendocrine effects of neuropsychotropic drugs and their possible influence ono toxic reactions in animals and man – the role of the dopamine-prolactin system

Arch. Toxicol.

Failure of steroid hormones to induce mammary growth in hypophysectomized rats

Endocrinology