Inano H, Suzuki K, Onoda M, Kobayashi H, Wakabayashi K
The First Research Group, National Institute of Radiological Sciences, Chiba-shi, Japan.
Cancer Lett. 1999 Apr 26;138(1-2):93-100. doi: 10.1016/s0304-3835(98)00378-4.
The role of prolactin in the initiation of mammary tumorigenesis by radiation was evaluated in ovarian hormone-free rats. Rats were bilaterally ovariectomized at 23 days of age, and then, at 2.5 months of age, two pituitaries obtained from mature rats of the same strain were transplanted underneath the kidney capsule as a means of increasing the serum prolactin level to provide stimulation of development of mammary glands. After 2 weeks, the ovariectomized rats with ectopic pituitary glands were exposed to whole body irradiation of 2.6 Gy of gamma-rays from a 60Co source and then treated with diethylstilbestrol as a tumor promoter. For the control, ovariectomized rats without ectopic pituitary glands were exposed and treated in the same way as the experimental group. A significant increase of serum prolactin level was observed at the time of irradiation by the pituitary transplanted rats, and intense immunohistochemical reaction with a specific anti-prolactin antiserum was detected in the ectopic pituitary glands. Also, mammary glands in the pituitary transplanted rats, ovariectomized before puberty, showed lactiferous ducts without alveolar buds at the time of tumor initiation. The pituitary transplanted rats showed a significantly increased incidence of adenocarcinoma and fibroadenoma compared with the control. Many of the mammary tumors induced in the pituitary transplanted rats given radiation were estrogen receptor (ER)(+) progesterone receptor (PgR)(+) and ER(+)PgR(-) tumors, whereas ER(-)PgR(-) tumors were mainly obtained in the control rats. In the experimental group, many of the fibroadenomas had low concentrations of ER and no PgR, while the adenocarcinomas had moderate concentrations of ER and high PgR. These results suggest that hypersecretion of prolactin from the pituitary transplants developed lactiferous ducts and accelerated the tumorigenesis of mammary glands initiated by radiation in the absence of synergism with ovarian hormones.
在无卵巢激素的大鼠中评估了催乳素在辐射引发乳腺肿瘤发生过程中的作用。大鼠在23日龄时进行双侧卵巢切除，然后在2.5月龄时，将取自同品系成熟大鼠的两个垂体移植到肾包膜下，以此提高血清催乳素水平，以促进乳腺发育。2周后，将带有异位垂体的去卵巢大鼠暴露于来自60Co源的2.6 Gy全身γ射线照射下，然后用己烯雌酚作为肿瘤促进剂进行处理。作为对照，将没有异位垂体的去卵巢大鼠以与实验组相同的方式进行照射和处理。垂体移植大鼠在照射时血清催乳素水平显著升高，并且在异位垂体中检测到与特异性抗催乳素抗血清的强烈免疫组化反应。此外，青春期前切除卵巢的垂体移植大鼠的乳腺在肿瘤起始时显示出有输乳管但无腺泡芽。与对照组相比，垂体移植大鼠的腺癌和纤维腺瘤发生率显著增加。在接受辐射的垂体移植大鼠中诱导产生的许多乳腺肿瘤是雌激素受体（ER）（+）孕激素受体（PgR）（+）和ER（+）PgR（ - ）肿瘤，而ER（ - ）PgR（ - ）肿瘤主要在对照大鼠中获得。在实验组中，许多纤维腺瘤的ER浓度低且无PgR，而腺癌的ER浓度中等且PgR高。这些结果表明，垂体移植导致的催乳素分泌过多促进了输乳管的发育，并在没有与卵巢激素协同作用的情况下加速了由辐射引发的乳腺肿瘤发生。
