The effect of oestrogens, testosterone and progesterone on the induction of cervico-vaginal tumours in intact and castrate rats

Abstract

OESTROGENS promote keratinisation in specific organs rather than generally as does vitamin A insufficiency (Gitlin, 1957), suppress the formation of mixed carcinomas of the uterine cervix in mice (Glucksmann and Cherry, 1962), and promote differentiation in the form of keratinisation in cervical tumours of mice (Klavins and Kaufman, 1962). This enhancement of keratinisation by oestrogens might be useful in the treatment of tumours refractory to radiation which often fail to respond to treatment with increased differentiation. This may be particularly useful for the mixed carcinomas of cervix which have given very poor results for both radiotherapy and surgery. On the other hand, oestrogens stimulate proliferation of the epithelium and stroma of the female genital tract, an effect that might be harmful to the patient if produced in tumours at these sites.The effect of castration, and of additional treatments with oestrogens, progesterone and testosterones have been studied experimentally mainly on mice and have yielded results varying with strain of mice, dosage and type of carcinogen, dosage and type of solvent for the sex hormones. Prolonged administration of oestrogens is followed infrequently by cervical tumours in mice (Gardner, 1959; Murphy, 1961), but in these experiments cholesterol pellets have been used as carriers and cholesterol itself induces cancers. Oestrogen treatment causes septic pyometra which may promote tumour formation, so that oestrogenic hormones may act only indirectly as carcinogenic agents (Gardner, 1953). Administration of oestrogens in combination with chemical carcinogens neither shortens the induction period nor increases the yield of cancers in intact mice (Murphy, 1961; Klavins and Kaufman, 1962; Laffargue, Samso, Luscan and Francois, 1963; Blanzat, Hirai and Pincus, 1966). In castrate mice treated with methylcholanthrene for 4 weeks only, subsequent administration of a diethylstilboestrolcholesterol pellet has increased the production of tumours and this effect was greater for a 33 % than for a 10 % hormone content of the pellet. The greater incidence of pyometra in mice treated with a 33 % as opposed to a 10 % oestrogenic pellet may account for the higher incidence of carcinomas (Murphy, 1961). Oestrogens do not alter the yield of cancers in spayed mice given full carcinogenic treatment by the thread method or painting. Taki (1967) reports an approximately equal stimulation of cancer production in castrate mice by the additional application of cholesterol alone, oestradiol in cholesterol and oestradiol only, if the treatment and observation period is limited to 5 weeks.

The Influence of Thyroactive Substances on the Induction of Cervico-vaginal Tumours in Intact and Castrate Rats

“…Similar adenomas occur in control intact and castrate rats of our colony (Glucksmann and Cherry, 1968) and none of the treatments in the present series of experiments has altered their incidence.…”

“…Castration inhibits and retards the appearance of sarcomas in the cervix and vagina of rats painted once weekly with DMBA (Glucksmann and Cherry, 1958).…”

“…In fact in intact animals oestrogens inhibit the induction of tumours (Glucksmann and Cherry, 1968). On the other hand, adrenalectomy, or the administration of cortisone, pelvic or whole body irradiation of spayed rats does not alter the atrophic status of the female genital tract, but accelerates and increases the induction of sarcomas even beyond the rate obtained in intact rats treated with the carcinogen only (Cherry and Glucksmann, 1960 On the other hand, castration causes atrophy of the epithelium and stroma of the cervico-vaginal tract and reduces the response to carcinogenic stimulation.…”

“…Castration causes atrophy of the vaginal epithelium and reduces the width of the stroma of the uterus and of the vagina to 40% and 48% respectively of that in intact animals (Glucksmann and Cherry, 1958). The volume of all these target tissues is restored to intact proportions by additional weekly treatment of castrates with 3 ,ug of oestradiol monobenzoate i.m.…”

The Effect of Thyroactive Substances on the Induction of Cervico-vaginal and Vulval Tumours in Castrate Rats at Various Levels of Carcinogenic Treatment

“…five. In addition to differences in tissue sensitivity which are influenced by castration (Glucksmann and Cherry, 1958) and by additional treatments Glucksmann, 1960 andGlucksmann and Cherry, 1968), the individual sensitivity plays a role. Thus the group of rats treated with Lthyroxine contained only one animal in which the cervico-vaginal stroma was very sensitive to five and one only was sensitive to 10 paintings.…”