Cyclosporine A-induced mammary hyperplasia and hyperprolactinemia in New Zealand White rabbits

Purpose: To investigate the potential activity of cyclosporin A (CsA) to in duce mammary hyperplasia in New Zealand White (NZW) rabbits. Methods: Female NZW rabbits were used throughout experiments. To simulate t he conditions of immunosuppression, CsA (10 mg/kg of body weight/d) was adm inistered intravenously on a daily basis for 14 days and methylprednisolone (5 mg/kg/d) was administered on the first two days. The CsA (10 mg/kg/d) a lso was administered without methylprednisolone for 14 days to another coho rt of rabbits. Mammary tissue of each rabbit was palpated and serially meas ured during this treatment period. The CsA was discontinued, and rabbits we re monitored for 14 more days during the washout period. Sequential plasma concentrations of prolactin, 17 betap-estradiol, and progesterone in each b lood sample were determined by use of radioimmunoassay. Results: All NZW rabbits treated with CsA and methylprednisolone for immuno suppression consistently developed striking mammary tissue hyperplasia. At the end of treatment with CsA and methylprednisolone, mammary glands had ex tensive changes consistent with actively lactating glands. Similar but less extensive hyperplasia developed in response to CsA alone. Plasma concentra tion of prolactin increased during treatment and decreased during the washo ut period. Plasma concentration of 17 betap-estradiol increased during trea tment and continued to increase during the washout period. Plasma progester one concentration decreased at the end of treatment. On discontinuation of CsA, mammary hyperplasia regressed. Conclusions: Cyclosporine A, with or without methylprednisolone, induces ma mmary hyperplasia and hyperprolactinemia in NZW rabbits. This rabbit model may be a reliable in vivo system by which to study immunosuppressant-induce d structural and functional changes of mammary glands similar to those obse rved in humans.