Hyperprolactinaemia and DNA synthesis in the pituitary gland of the rat

Hyperprolactinaemia produced in rats by the transplanted prolactin-secreting tumours MtTW15 and 7315a significantly (P<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<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 (α-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.