Prolactin binding to R3230AC mammary carcinoma and liver in hormone-treated and diabetic rats

Abstract

Specific 125I-labeled prolactin binding was measured in membrane particles prepared from R3230AC mammary carcinoma and liver of tumor-bearing Fischer rats after either prolactin, estrogen, or lergotrile mesylate treatment, or after the induction of diabetes by streptozotocin. Hormone binding to tumors was decreased by treatment with prolactin (0.5 or 1 mg/day) or estradiol valerate (7.5 mg/kg/week). In contrast, prolactin treatment did not affect prolactin binding to liver membrane particles, but estradiol valerate treatment resulted in a four-fold increase in prolactin binding to this tissue. Lergotrile mesylate, which lowers plasma prolactin levels, did not affect tumor growth or prolactin binding to either tumor or liver. Prolactin binding to both tumor and liver was significantly reduced in diabetic rats, suggesting that insulin may play an important role in controlling tissue sensitivity to prolactin. Specific binding of 125I-labeled prolactin to enzymatically dissociated cells from R3230AC tumors was demonstrated in vitro. The binding capacity of the cells was found to be of the same order of magnitude as the binding capacity in membrane preparations when appropriate corrections were applied for yields of cells and membranes. R3230AC tumor, which is responsive to prolactin appears therefore to be a useful model system for further study aimed at elucidation of growth and metabolic response to the hormone prolactin in breast cancer.

PIP: Specific iodine-125-labeled prolactin binding was measured in membrane particles prepared from R3230AC mammary carcinoma and liver of tumor-bearing Fischer rats after either prolactin, estrogen, or lergotrile mesylate treatment, or after the induction of diabetes by streptozotocin. Hormone binding to tumors was decreased by treatment with prolactin (.5 or 1 mg/day) or estradiol valerate (7.5 mg/kg/week). In contrast, prolactin treatment was without affect on prolactin binding to liver membrane particles, but estradiol valerate treatment resulted in a 4-fold increase in prolactin binding to this tissue. Lergotrile mesylate, which lowers plasma prolactin levels, had no affect on tumor growth or prolactin binding to either tumor or liver. Prolactin binding to both tumor and liver was significantly reduced in diabetic rats, suggesting that insulin may play an important role in controlling tissue sensitivity to prolactin. Specific binding of iodine-labeled prolactin to enzymatically dissociated cells from R3230AC tumors was demonstrated in vitro. The binding capacity of the cells was found to be of the same order of magnitude as the binding capacity in membrane preparations when appropriate corrections were applied for yields of cells and membranes. R3230AC tumor, which is responsive to prolactin, appears therefore to be a useful model system for further study aimed at elucidation of growth and metabolic response to the hormone prolactin in breast cancer.