Expression Of PRA, PRB And Effect Of PRA, PRB In Local Deficient Estrogen Metabolism And Progesterone Resistance In Endometriosis

[Objective]To investigate the expression of Progesterone receptor subtype A (PRA) and PRB in eutopic and ectopic endometrium throughout the menstrual cycle and its effect in local deficient estrogen metabolism and progesterone (P) resistance in endometriosis. [Method]By PT-PCR and immunohistochemistry LBP methods, we assess the P450arom(P450A) expression of 67 ectopic endometrium cases(including 45 ovarian endometriosis and 22 peritoneal endomtriosis), 32 eutopic endometrium and 35 normal uterine endometrium throughout the menstrual cycle; By RT-PCR method, we assess the level of 17β-hydroxysteroid dehydrogenase type 2 messenger RNA(mRNA). The same experiment methods were used to determine mRNA and protein level of PRA, PRB and PRAB(PRA+PRB) in the above cases. We observed the difference between the ectopic endometriosis and eutopic endometriosis at histological structure level. [Results ]1. P450A mRNA level was higher in the ectopic endometrium than in eutopic endometrium (P < 0.01) . P450A mRNA was present in only 1 of 35 normal uterine endometrium samples. No statistically significant differences of P450A mRNA level was found between ovarian endometriosis and peritoneal endomtriosis (P > 0.05) . The expression characteristic of P450A protein is the same as one of P450A mRNA in ectopic endometrium.2. In all endometriotic samples, no detectable 17β-hydroxysteroid dehydrogenase type 2 mRNA could be demonstrated, however, its expression in eutopicendometrium and 35 normal uterine endometrium was low in the late proliferative phase of the menstrual, and its level was increased in the secretory phase, its highest concentrations occurred during the late secretory phase. The expression level of 17β-hydroxysteroid dehydrogenase type 2 mRNA was lower in eutopic endometrium than in normal uterine endometrium. 3. By microscope, we obviously observed glandular epithelium and stroma cells in ovarian endometriomas and glands in the part of the samples, but the stroma cells was dominant, the development of etopic endometrium has no cyclic variation. There are abundant of vascular network. The stroma of ovarian endometriosis invasive the ovarian tissue.4.Compared with normal endometrium, in ovarian and peritoneal endometnosis, the expression of PRB and PR(A+B)mRNA was statistically significantly lower(P<0.01) during the proliferative, the early secretory and the midsecretory phase, but significantly higher (P<0.01) during the late secretory phase. The ratio of PRB to PR(A+B) mRNA was significantly higher in ovarian endometriosis(P < 0.01) than normal endometrium; the ratio of PRB to PR(A+B) mRNA was significantly lower in peritoneal endomtriosis ( P < 0.01 ) than normal endometrium during the menstrual cycle.The expression of PRB and PR(A+ B)mRNA was no cyclic variation thoughout the cycle.5. Compared with normal endometrium, in ovarian endometriosis, the expression of PRB,PRA and PR(A+B) protein in the glandular epithelium was statistically significantly lower (P<0.01) , however, PRA was reduced markedly during the menstrual cycle; in the stroma, the expression of PRB was statistically significantly higher (P<0.01) and the expression of PRA and PR(A+B) protein shows no difference (P > 0.05) .In the glandular epithelium and stroma cell, the ratio of PRB / PR(A+B) and the ratio of PRB / PR(A+B) protein in ovarian endometriosis was significantly higher (P < 0.01) than normal endometrium.The expression of PRB and PR(A+B) protein was no cyclic variation throughout thecycle.6. In eutopic endometrium of endometriosis, the mRNA and protein expressionof PRA, PRB and PR(A+B) was the same as the normal endometrium. [Conclusion]1. The balance of local estrogen biosynthesis and catabolism was impaired in ovarian and peritoneal endomtriosis due to the abnormal expression of P450arom and a deficiency of the enzyme 17β-hydroxysteroid dehydrogenase Type 2.2. The abnormal interaction between glandular epithelium and stroma may play a important role in endometriotic implants.The relatively or absolutely increased PRB and relatively decreased PRA levels suggest that the endometriotic stroma probably play a primordial role in the development and growth of endometriosis.3. The abnormal expression of PRA, PRB, PR (A+B) and the abnormal ratio of PRB to PRA may be responsible for the local progesterone resistance in endometriosis, which probably induce P450arom and fail to induce 17β -HSD type 2 ,by which estrogen is up-regulated.4. Progesterone resistance may be an important part of the mechanism in the development of endometriosis.