Mammary Glands and Spontaneous Tumors Nuclear Thyroid Hormone Receptors in C3H/HeN Mouse

Saturable, high-affinity binding sites for 3,5,3'-triiodo-u-thyronine (T3) were identified in isolated nuclei and solubilized chromatin extracts of mammary glands, spontaneous mam mary tumors, and liver from C3H/HeN mice. Receptor concen tration in whole mammary gland nuclei (254 fmol/mg DMA) was only about one-half that of mouse liver nuclei (536 fmol/ mg DNA), but in molecular weight (55,000) and in their affinity for various thyroid hormone analogues, the binding was essen tially identical. Saturation analysis of T3 binding in a series of individual spontaneous mammary tumors and pooled lactating mammary glands indicated that the concentrations of la-bind ing sites of the mammary gland are conserved in the transition to neoplasms and are somewhat increased in the largest tu mors. Thyroxine binding was identical in capacity to T3 binding in mammary gland nuclei and nuclear extract but showed a higher binding capacity than did T3 in the largest tumors. High-performance molecular exclusion chromatography did show a difference between mammary gland and liver in the distribution of competible [125I]T3binding between two macromolecular forms; the excluded peak (M, > 450,000) comprised 56% of the T3 binding in the liver but only 9% in the mammary gland with the included peak (M, 55,000) contributing the balance of binding in each case. Spontaneous mammary tumor resembled the mammary gland in the macromolecular distri bution of specific T3 binding (16% excluded). Thymidine uptake showed only a modest decrease in the larger tumors (>2.0 g), while nuclear histone acetylase activity was significantly decreased in this group. Neither measurement showed a significant correlation with T3 or thyroxine binding capacity.