Effects of Hypothyroidism and Progesterone on Mammary Tumours Induced by 7,12-Dimethylbenz(a)anthracene in Sprague-Dawley Rats

Abstract

Summary.-Hypothyroidism, alone or combined with progesterone, significantly decreased 7,12-dimethylbenz(a)anthracene (DMBA) mammary tumorigenesis relative to controls. However, the decrease was less in the progesterone-treated group, and statistical analysis showed that progesterone enhanced tumorigenesis to the same extent in hypothyroid animals as in the controls. Most tumours in hypothyroid progesterone-treated rats were adenocarcinomata; in the absence of the hormone most tumours were benign. However, the difference between the tumour types in the 2 groups was not statistically significant.The morphological changes observed in the endocrine glands, genital tracts and non-neoplastic mammary tissue, considered in relation to previously reported data, suggest that hypothyroidism reduced the tumour yield mainly by secondarily inhibiting somatotrophin production and secretion, although the effect of decreased food intake could not be excluded completely. The higher tumour yield in the hypothyroid progesterone-treated rats may have been due to higher circulating levels of prolactin in this group compared with those in the hypothyroid group which received no hormone. INDUCTION of mammary tumours by7,12-dimethylbenz(a)anthracene (DMBA) is influenced markedly by the hormonal environment of the animal. Progesterone, while not carcinogenic per se, significantly enhances DMBA mammary tumorigenesis in entire rats when hormone injections are begun just before or after carcinogen administration (Jabara, 1967;Jabara and Harcourt, 1970). By contrast, ovariectomy performed 7 days before feeding DMBA totally inhibits mammary tumour development (Jabara and Harcourt, 1970) whereas adrenalectomy has no significant effect on tumorigenesis (Jabara and Harcourt, 1971). Reported effects of hypothyroidism on mammary tumour induction range from an enhancement of carcinogenesis Thomas, 1966, 1967;Davidson, Owen and Thomas, 1969)

Progesterone: An overview and recent advances

“…Poel (236) found that progesterone (0.25 ml of 5% progesterone in peanut oil sc/week for 19 weeks) accelerated the development of 20-methylcholanthrene-induced mammary tumors in mice. When 7,12-dimethylbenz[a]anthracene (DMBA) was used as a carcinogen, mammary tumorigenesis was significantly enhanced by progesterone treatment if begun just before or after carcinogen administration in intact rats (237) or if given continuously after dimethylbenzanthracene treatment in hypothyroid rats (238). When, on the other hand, progesterone was administered before feeding dimethylbenzanthracene, it prevented the onset of mammary cancers (239) as shown by a reduction in tumor yield; continuation of progesterone after carcinogen administration, however, lessened this reduction in tumor yield (240).…”

Nematic liquid crystal for gas-liquid chromatographic separation of steroid epimers

“…Androgen sensitivity and steroid binding has been studied in prostate cancer in rats (2). Furthermore, a considerable level of research is currently being directed toward investigations of the involvement of steroids in human breast cancer (e.g., (3)), as well as in 7,12-dimethylbenz[o]anthracene-induced mammary tumors in experimental animals (4)(5)(6)(7)(8)(9)(10). In steroid biochemical studies, research has been substantially aided by the availability of useful analytical techniques for separation and measurement.…”