Anti-oestrogenic effects of tamoxifen on mammary gland and hypophysis in female rats

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Abstract
Adult ovariectomized rats were treated for 14 days with oestradiol benzoate (E2B) 15 μg/kg/d and oestradiol benzoate 15 μg/kg/d + progesterone (PRO) 15 mg/kg/d for induction of mammary gland parenchymal stimulation. Histological examination and whole mount preparation demonstrated that ductal growth in the mammary gland after E2B treatment was completely antagonized by tamoxifen (TAM) 0.5 mg/kg/d. Parallel DNA concentrations in the mammary gland were decreased to control levels by TAM 0.5, 5 and 15 mg/kg/d. E2B-induced hyperprolactinaemia in the forenoon (basal secretion was equally reduced by TAM 0.5, 5 and 15 mg/kg/d). In the afternoon, when prolactin (Prl) secretion is at its maximum, TAM 0.5 mg/kg/d turned out to be ineffective to abolish Prl surge, but TAM 5 and 15 mg/kg/d reduced serum Prl concentrations in a doserelated manner. Immunoperoxidase staining of Prl cells in the pars distalis of the hypophysis indicated that adaptive hypertrophy and signs of hypersecretion after E2B were abolished by TAM 5 mg/kg/d. Luteotrophic cells clearly showed cellular atrophy, regression and secretory inactivity. Maximal tubulo-alveolar mammary parenchymal stimulation in rats treated with E2B-PRO was slightly inhibited by TAM 0.5 mg/kg/d. Histology showed a small disseminated parenchymal islet. DNA concentrations only were partially decreased by the anti-oestrogen though serum Prl concentrations were found to be completely decreased to control levels. Secretory activity of Prl cells was reduced by TAM 0.5 mg/kg/d. In E2B-PRO treated rats lisuride had poor inhibitory activity on Prl levels and none on DNA concentrations in the mammary gland. Combined treatment with TAM and lisuride significantly decreased DNA concentration in the mammary gland compared to animals which received E2B-PRO. Also Prl levels were at a minimum. Histology performed on the mammary gland showed only slight tubulo- but no tubulo-alveolar activation. Luteotrophic cells in the pituitary gland stained by the immunoperoxidase technique appeared regressive, shrunken and atrophied.

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