STUDY OF THE ROLES OF PTH RELATED PEPTIDE (PTHrp) IN REPRODUCTION AND GYNECOLOGIC TUMOR

(1)正常女性生殖器官中PTHrP基因表达和PTHrp分子的存在。(a)RT-PCR检测子宫内膜、蜕膜、绒毛、输卵管、卵巢、子宫肌、胎膜、胎儿肝、肠、皮肤组织中PTHrP基因的表达。(b)免疫组化结果显示，PTHrP在子宫内膜细胞、子宫内膜细胞、蜕膜组织间质细胞、绒毛细胞、胎膜蜕膜间质细胞、绒毛合体中呈阳性表达。(c)哺乳期产妇乳汁中PTHrP含量高，血清中PTHrP含量也高，提示乳汁中PTHrP向哺乳期产妇血流中转移。(d)妊娠中期羊水PTHrP浓度最高。羊水过多和畸形儿组羊水PTHrP浓度与正常对照组无显著性差异，但死亡性脱水组羊水PTHrP浓度较正常对照组低。(e)卵泡液中PTHrp含量较高，且不受雌、孕激素水平的影响。(2)卵巢良恶性肿瘤组织中PTHrP基因的表达及其临床意义(a)PTHrP基因在良、恶性肿瘤组织中均有表达。(b)本文用放射免疫分析法测定了34例卵巢良性肿瘤、27例卵巢恶性肿瘤、5例卵巢良性肿瘤、10例卵巢恶性肿瘤患者腹水及囊液中PTHrP的含量。良性肿瘤患者血清PTHrP水平明显升高，占8%;恶性肿瘤患者血清PTHrP水平明显升高，占35%。33%的恶性肿瘤患者腹水和囊液PTHrP浓度很高（> 500 pmol/L）。这些结果表明，PTHrP测定是有用的肿瘤标记物在某些情况下，卵巢肿瘤。

(1) PTHrP gene expression and presence of PTHrp molecule in normal female reproductive organs.(a) PTHrP gene expression was confirmed by means of RT-PCR in endometrium, decidua, villi, tube, ovary, and uterine muscle as well as fetal membrane and fetal liver, intestine and skin.(b) Immunohistochemical analysis showed that PTHrP was positively stained in endometrial cells in endometrium, endometrial cells, stromal cells in decidual tissue, chorionic cells, decidual stromal cells in fetal membrane, syntijtium in chorionic villi.(c) High concentration of PTHrP was present in milk of lactating puerperal women, in whom serum PTHrP concentration was high, suggesting the transfer of milk PTHrP to the blood stream of lactating puerperal women occured.(d) PTHrP concentration in amniotic fluid was the highest in second trimester during pregnancy. Amniotic fluid PTHrP concentration in hydroamnios and pregnancies with anomalous fetus was not different from normal controls expect for thanatophoric dwrafism in which PTHrP concentration was lower.(e) Follicular fluid contained high concentration of PTHrP.PTHrp levels seemed not tobe affected by estrogen or progesterone levels in follicular fluid.(2) PTHrP gene expression in tissues of ovarian benign and malignant tumors and clinical signific ance of PTHrP in patients with ovarian tumors.(a) PTHrP gene expression was seen in tissue of both benign and malignant tumors.(b) PTHrP concentration was determined by means of RIA in sera of patients with benign ovarian tumors (n=34), malignant ovarian tumors (n=27) and ascites and cystic fluid (from benign tumors, n=5, malignant tumors, n=10). High serum levels of PTHrP were seen in 8 % of cases with benign tumors and in 35 % of cases with malignant tumors. Concentration of PTHrP in asctic and cystic fluid was very high (more than 500 pmol/L) in 33 % of malignant cases. These results suggest that PTHrP determination is useful a tumor marker in some cases of ovarian tumors.