Burdman J A, Calabrese M T, MacLeod R M
J Endocrinol. 1983 Apr;97(1):65-74. doi: 10.1677/joe.0.0970065.
Hyperprolactinaemia produced in rats by the transplanted prolactin-secreting tumours MtTW15 and 7315a significantly (P less than 0.01) inhibited by 70% the incorporation of [3H]thymidine into the pituitary DNA of the host animals. The weight and the DNA content of the glands were significantly (P less than 0.01) reduced by 30%. The administration of haloperidol, a dopamine receptor blocking agent, to the tumour-bearing rats increased the suppressed DNA replication in the anterior pituitary glands by approximately 560% in the MtTW15-bearing rat and by 100% in the 7315a-bearing animals. Furthermore, injection of drugs which stimulate prolactin release either by blocking the synthesis of dopamine (alpha-methyl-p-tyrosine) or the re-uptake of dopamine (reserpine) stimulated DNA synthesis by 800 and 100% respectively in the anterior pituitary gland of rats bearing the MtTW15 tumour. In contrast, lisuride, a dopamine agonist, significantly inhibited the incorporation of [3H]thymidine into the DNA of the pituitary gland of normal but not hyperprolactinaemic rats. Chronically administered oestrogens to hyperprolactinaemic rats increased the weight (100%). DNA content (31%), incorporation of [3H]thymidine into DNA (680%) and synthesis and release of prolactin (300%) in the pituitary gland. The incorporation of [3H]thymidine into tumour DNA was several times higher than in the pituitary gland of the host animal and was not significantly modified by any of the above treatments. Likewise the hyperprolactinaemia of the tumour-bearing rats was not significantly changed. In conclusion, we have shown that hyperprolactinaemia inhibits DNA synthesis in the anterior pituitary gland and this inhibition can be reversed completely by a dopamine receptor blocking agent and by hypothalamic dopamine depleting drugs. We propose that dopamine regulates, either directly or indirectly, DNA synthesis in the lactotrophs of the pituitary gland, which may be responsive to negative feedback mechanisms.
移植分泌催乳素的肿瘤MtTW15和7315a在大鼠中产生的高催乳素血症显著（P小于0.01）抑制了[3H]胸苷掺入宿主动物垂体DNA达70%。腺体的重量和DNA含量显著（P小于0.01）降低了30%。给荷瘤大鼠施用多巴胺受体阻断剂氟哌啶醇，在携带MtTW15的大鼠中，使垂体前叶中受抑制的DNA复制增加了约560%，在携带7315a的动物中增加了100%。此外，注射通过阻断多巴胺合成（α-甲基-p-酪氨酸）或多巴胺再摄取（利血平）来刺激催乳素释放的药物，在携带MtTW15肿瘤的大鼠垂体前叶中分别使DNA合成增加了800%和100%。相比之下，多巴胺激动剂麦角乙脲显著抑制了正常大鼠而非高催乳素血症大鼠垂体DNA中[3H]胸苷的掺入。长期给高催乳素血症大鼠施用雌激素，增加了垂体的重量（100%）、DNA含量（31%）、[3H]胸苷掺入DNA的量（680%）以及催乳素的合成和释放（300%）。[3H]胸苷掺入肿瘤DNA的量比宿主动物垂体中的高出数倍，且未因上述任何处理而发生显著改变。同样，荷瘤大鼠的高催乳素血症也没有显著变化。总之，我们已经表明高催乳素血症抑制垂体前叶中的DNA合成，并且这种抑制可以被多巴胺受体阻断剂和下丘脑多巴胺耗竭药物完全逆转。我们提出多巴胺直接或间接调节垂体催乳细胞中的DNA合成，催乳细胞可能对负反馈机制有反应。
