How to prepare animal models of induced pituitary tumors?

     [Simulation mechanism] Long-term stimulation with estrogen can induce PRL tumors in the pituitary gland of rats. The specific mechanism has not been fully elucidated. For example, after long-term administration of estrogen to F344 rats, the glands may grow abnormally into tumors after a few weeks, reaching 10 to 20 times the size of normal pituitary glands. Other sensitive rat strains include AxC-Irish (ACI), Wistar-Furth and Copenhagen (COP). Holtzmann, Sprague Dawley and Brownorway rats have been fed estrogen for a long time, and their pituitary glands are still normal.

  [Modeling method] Take Wistar-Furth rats weighing 60-80g, regardless of their hermaphrodite. Dissolve diethylstilbestrol (DES) in sterile peanut oil. The experimental group was intraperitoneally injected with 5 mg/kg DES. The negative control group was injected with the same amount of peanut oil, and the normal control group was punctured twice a week without injection. They run randomly for 4, 8 and 12 weeks. Serum was collected by radioimmunoassay to measure PRL, and the pituitary was weighed for histopathology and immunohistochemistry.

  [Characteristics of the model] The average body weight of the pituitary gland and serum PRL of the rats taking diethylstilbestrol 8 weeks later was significantly higher than that of the negative control group. H&E staining under an optical microscope showed a significant increase in the number of cells and widening of bands, indicating that the cytoplasm is round or polygonal, with different sizes of nuclei, deep staining, and atypical nuclei. possible. The tumor is congested, new blood vessels are visible, and the glandular structure is usually lost. At 12 weeks, 100% tumor-like changes appeared, the pituitary gland was significantly larger than the negative control group, and intratumoral bleeding was observed.

       [Model evaluation and application] Estrogen-induced pituitary tumors have the following characteristics: (1) The occurrence of induced tumors is related to genetics, and there are strains with high and low induction rates. For example, F344 rats have 100% induction, while Holtzmann rats have 2-6% induction. ②Estrogen dependence. With the continuous administration of estrogen, the pituitary gland changes from proliferative to neoplastic, and the withdrawal of estrogen causes the induced tumor to gradually shrink or disappear. Therefore, some scholars believe that most of the pituitary changes in rats treated with estrogen are proliferative changes rather than tumor formation. The reason is as follows. ① "Tumors" caused by estrogen cannot be transplanted into rats that have not been treated with estrogen. However, certain induced tumors can continue to grow to certain stages without relying on estrogen. Animal models of estrogen-induced pituitary tumors are as easy to create as human PRL tumors, and are widely used in basic and clinical research on pituitary PRL tumors. This model can be used to study the pathogenesis, pathogenesis, clinical treatment and drug development of pituitary tumors.