Effects of 6-methylenetestosterone acetate on spontaneous mammary tumourigenesis in SHN mice.

The effects of 6-methylenetestosterone acetate (MTA), an androgen derivative, on spontaneous mammary tumourigenesis were studied in a high mammary tumour strain of SHN virgin mice. AT 5-6 months of age female litter mates were divided into the experimental and the control mice. The experimental mice were given subcutaneous implantations of Silastic capsules containing MTA (MTA1 group) and non-tumourous mice received additional Silastic capsules after 2 months (MTA2 group) followed by MTA pellet implantation to non-tumourous animals a further 2 months later (MTA3 group). The control mice received Silastic capsules containing cholesterol and cholesterol pellets with the same design as in the experimental groups. In the MTA1 group, there was no effect on mammary tumourigenesis when treated mice were compared to the controls. In the MTA2 group, mammary tumour incidence tended to be lower in the experimental mice than in the controls, while in the MTA3 group mammary tumourigenesis was significantly suppressed in the experimental mice compared to the controls. Associated with these effects, normal mammary gland growth was inhibited and serum prolactin level was reduced in both the MTA2 and MTA3 treated mice. The ovarian weights were decreased in the experimental mice of the MTA1 group, while the adrenal weights were lower in the MTA2 or MTA3 group when compared to respective control values. Ovaries and adrenals did not differ histologically between any of the groups. A prolonged oestrous/metoestrous stage was observed only in the experimental mice of the MTA1 group. The results indicate that MTA has two opposing effects on mammary tumourigenesis according to its dose; thus a low dose has little effect on mammary tumourigenesis, while higher doses inhibited both normal and neoplastic mammary gland growth probably through the inherent androgenicity of MTA.