Regulation of estrogen-binding capacity by insulin in 7,12-dimethylbenz(a)anthracene-induced mammary tumors in rats.
The role of insulin as a regulator of estrogen receptors (ER's) was investigated in 7,12-dimethylbenz(a)anthracene-induced mammary tumors in diabetic and insulin-treated rats. Induction of diabetes with streptozotocin produced regression of lesions classified as insulin dependent; lesions that continued to grow in diabetic rats were classified as insulin independent. Compared to tumors in intact hosts [ER, 39 +/- 4 (S.E.) fmol/mg cytosol protein], regressing insulin-dependent lesions had ER levels of 8.5 +/- 0.7 fmol, and insulin-independent tumors had ER levels of 24 +/- 3 fmol. Treatment of diabetic rats with insulin 8 IU/day, caused insulin-dependent regressing tumors to resume growth; these lesions had ER levels of 53 +/- 10 fmol. Insulin-independent lesions in diabetic rats demonstrated two patterns after treatment with insulin; continued growth resulted in tumors having ER levels of 28 +/- 11 fmol, whereas insulin-induced tumor regression resulted in tumors that demonstrated ER levels of 40 +/- 6 fmol/mg cytosol protein, a value equal to the level of ER in tumors growing in intact rats. Scatchard analysis of the saturation-binding data gave linear representations, and the estimated Kd for the ER was comparable for all groups, ranging from 0.44 to 1.90 x 10(-9) M. Several additional tumors were classified as demonstrating static growth. When this behavior represented a response due to insulin treatment, ER levels were elevated. Static tumors remaining static after insulin treatment demonstrated low ER levels. We conclude that (a) cessation of tumor growth after induction of diabetes resulted in reduction of ER levels, (b) treatment with insulin that resulted in an altered tumor growth was accompanied by elevated ER levels, and (c) insulin may play a role in regulation of ER independent of tumor growth.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism; D005260:Female; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism*
D007328:Insulin; D011960:Receptors, Estrogen; D015127:9,10-Dimethyl-1,2-benzanthracene