The Study Of The Relation Between Estrogen Or Androgen And Mechanism Of Benign Prostatic Hyperplasia

1. OBJECTIVETo investigate the role of estrogen and androgen in the prostate of castrated rat; to study the relation between BPH and estrgen/androgen or the change of mitosis orientation in the prostate epithelia cells of male rats; and it is possible mechanism.2. METHODS222 SD male rats with 3 months and 56 SD male rats with 4 months were used. To divide 3 months rats into 37 groups at random: 35 groups of different estrogen/androgen, normal control and castrated control group; to divide 4 months rats into 7 groups at random: testosterone propionate (TP), benzogynestry (E₂) and control group. Before the experiment, all rats were castrated under anaesthesia. 3 months rats began administration after 1 week(Medicine administration teams were injected different doses of estrogen/androgen and control groups were injected isotonic Na chloride one month); howerver, 4 months rats were treated with a single injection of testosterone propionate (TP) or benzogynestry (E₂) after 1 month. 24h after last injection, we collected their blood,killed rat and obtained tissues. In addition, all 4 months rats were injected intraperitoneally with bromodeoxyuridine (2mg/100g) at 2 hours before the tissues were removed. All tissues were stained with haematoxylin-eosin, specific stain and immunohistochemistry staining. The prostate tissue of 4 months rats were made gene array and RT-PCR.3. RESULTSOne month of administration experiment: When the doses of testosterone propionate(TP) was 0.02, 0.1, 0.5, 2.5å’Œ12.5 mg per rat, the degree of prostatic hyperplasy is not negative correlation with the dose of benzestrofol. When the dose of TP was 0.10 mg per rat, with the increasing of the dose of benzestrofol, the volume and quotient of prostate were increasing. But when the dose of benzestrofol was 50ug/kg, the area of prostate glandular cavity increased and a little AR appeared, and with the increasing of the dose of benzestrofol, the prostate was not increasing again.A single administration experiment: All mitoses found in prostate epithelia cells of castrated rats with TP(the group of 24, 36 and 48h) were oriented parallel to the basement membrane, however mitoses found in prostate epithelia cells of castrated rats in control group and E groups(the group of 24, 36 and 48h) were oriented perpendicular to the basement membrane. TP treatment was resulted in marked changes in mitosis orientation in prostate epithelia cells. The BrdU-labelled positive cells can be seen throughout the stroma and prostate epithelia cells with injection of TP, however, the positive cells can only be seen in stroma of E₂ groups and hardly be seen in the control group. This present study showed a new effect of TP, which could make remarkable change on mitosis orientation in the epithelia cells of the prostate. The effect of TP on mitosis orientation has also been examined in other tissues such as liver, jejunum, colon and skin tissues through immunohistochemistry examination and iron haematoxylin-eosin staining process. No noticeable effects were found in these tissues. Gene array and RT-PCR comfirmed that the genes of cell proliferation of TP group were up-regulation 2 fold, such as RAN, TGM4 and Wnt2 in Wnt signaling way and et al. On the other hand, the suppressor genes were 2 fold down-regulation like DKK3, Fas and et al.4. CONCLUSION(1) That estrogen produces a marked effect is on the base of androgen existence. E/T played a role in prostate diseases.(2) It was a marked change of mitosis orientation in prostate epithelia cells.(3) This process maybe related to Wnt signaling pathway and AR singling pathway, which controled mitosis orientation and cell proliferation and enhanced BPH.