P450 arom y microambiente estrogénico en endometrios eutópicos de mujeres con endometriosis / P450Arom and estrogenic microenvironment of eutopic endometria in endometriosis

Background: Endometriosis, a common gynecologic disorder characterized by endometrial glands and stroma outside the uterus, is diagnosed by direct visualization of peritoneal and ovarian implants during laparoscopy. Aim: To study the estrogenic microenvironment in eutopic endometria of women with and without endometriosis. Patients and methods: Eutopic endometria, obtained during laparoscopy from 23 women with endometriosis and 20 fertile cyclic women undergoing tubal sterilization, was studied. P450Arom mRNA expression (RT-PCR) was measured. Also, P450Arom activity was assessed measuring testosterone conversion to estradiol and the concentration of this last hormone in cultured endometrial explants. Results: Age and body mass index was similar in both groups studied. Seventy nine percent of endometria from women with endometriosis and in 29.4 percent from control group expressed P450Arom mRNA (p <0.01). The intensity of the band was higher in secretory endometria from women with endometriosis when compared to controls (p <0.01), but it was similar during the proliferative phase. Estradiol secretion to the culture media by proliferative endometria explants from women with endometriosis was 3-fold higher than secretory endometria (p <0.01) and endometria from control women in both phases. P450Arom activity, in the presence of testosterone, was 7-fold higher in endometrial cultures from women with endometriosis, when compare with the basal culture (p <0.01). However, in endometrial explant cultures from control women, this activity was not statistical different. Conclusions: These results indicate that in women with endometriosis, the microenvironment in the endometria is estrogenic as a consequence of an increased expression and activity of the P450 Arom.

Embryo-endometrial proteases during early mammalian development.

In mammals, extensive remodeling of uterine endometrial matrix occurs during reproductive cycle and blastocyst implantation. This is regulated by a variety of molecules such as hormones, growth factors, cytokines and proteases. In this article, we review the current state of knowledge available on various proteases and their inhibitors functionally involved in the embryo-endometrial tissues and present some data on endometrial proteases in hamsters and rats during estrous cycle and early pregnancy. We demonstrate the presence of at least four gelatinolytic activities in endometrial samples, belonging to gelatinase-A and -B categories and their dependence on calcium/zinc ions for enzyme activity and, their interrelationships between zymogen and active forms. We believe that the embryo-endometrial proteases are essential for hatching of blastocysts and for the dynamic remodeling of endometrial tissues, occurring during the critical peri-implantation period.

Telomerase and telomere length in normal and malignant human endometrium as prognostic markers.

Telomerase activation and telomere length maintainence are thought to be essential for cellular immortality and oncogenesis. Normal human endometrium expresses significant telomerase activity in a menstrual phase dependent manner. In this report, we have evaluated telomerase activity and telomere length in post menopausal endometrial hyperplasias and endometrial cancers to study their usefulness as prognostic markers. Telomerase activity was measured by the TRAP assay (Boehringer Mannheim, Germany) and telomere restriction fragment (trf) by the telomere length assay kit (BD Pharmingen). Proliferation markers PCNA and Bcl2 were studied by immunohistochemistry. Senescence associated Ogal activity was studied simultaneously and correlated with the above markers. Strong telomerase activity was observed in the proliferative phase of the normal endometrium, endometrial cancers and post-menopausal endometrial hyperplasias compared to normal, secretory and resting phases of the endometrium. PCNA and Bcl2 showed high positivity in telomerase positive cases. Telomerase activity was inversely proportional to Ogal activity. Mean trf lengths became shortened as the normal tissues underwent neoplastic changes. Our study suggests that high telomerase activity and short telomere lengths could be useful prognostic markers in human endometrium.

Expression of 3b-Hydroxysteroid dehydrogenase and P450 side chain cleavage enzyme in the human uterine endometrium

The enzyme complex 3b-hydroxysteroid dehydrogenase/delta(5)-delta(4)-isomerase (3beta-HSD) is involved in the biosynthesis of all classes of active steroids. The expression of 3beta-HSD in human uterine endometrium during the menstrual cycle and decidua was examined in an effort to understand its role during ova implantation. 3beta-HSD was weakly expressed in the glandular epithelium of the proliferative phase and moderately expressed in the glandular epithelium of secretory phase of the endometrium. In the decidua of the ectopic pregnancy, 3beta-HSD was strongly expressed. The human uterine endometrial 3beta-HSD was identified as being the same type as the placental 3beta-HSD by RT-PCR and sequence analysis. In addition to the expression of 3beta-HSD, P450scc was expressed in the decidua of the ectopic pregnancy. These results suggest that pregnenolone might be synthesized from cholesterol by P450scc de novo and then, it is converted to progesterone by 3beta-HSD in the uterine endometrium. The data implies that the endometrial 3beta-HSD can use not only the out-coming pregnenolone from the adrenal gland but also the self- made pregnenolone to produce progesterone. The de novo synthesis of progesterone in the endometrium might be a crucial factor for implantation and maintenance of pregnancy.

Study on the effects of FCu-IUD and FICu-IUD on matrix metalloproteinases in human uterine flushing and endometrium / 华中科技大学学报（医学）（英德文版）

The activity of matrix metalloproteinases (MMPs) in the uterine flushing and endometrial tissue of normal adult women wearing FCu-IUD (fixed Cu-IUD) or FICu-IUD (indomethacin-releasing FCu-IUD) was observed by using zymography on SDS-PAGE containing gelatin. The results showed that the activity and kinds of MMPs in FCu-IUD group were increased significantly as compared with themselves before being inserted FCu-IUD. However, compared with the FCu-IUD group, the activity of some kinds of MMPs in the FICu-IUD group was decreased significantly. These data suggest that IUD can enhance the activity of MMPs in human endometrium, intermediated by prostaglandins, and MMPs may have relation to IUD-induced menorrhagia and indomethacin reduces IUD-induced menorrhagia by partly inhibiting MMPs synthesis.

Enhanced expression of urokinase-type plasminogen activator in the rat endometrium following induction of decidualisation.

Urokinase-type plasminogen activator(uPA) assayed in uteri of cycling and deciduoma bearing rats shows detectable levels of this enzyme in endometrium. Zymographic analysis confirms uPA of decidual tissue and, following artificial induction of decidualisation, uPA activity constantly increases in the decidualising endometrium reaching a peak on day 9 of pseudopregnancy. Endometrial uPA of nonpregnant rats does not show any significant change during estrous cycle. Results are discussed in relation to expression of this activator in endometrium of rats during morphogenesis of decidual cells.