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.

Cytochrome P450c17alpha 5'-untranslated region *T/C polymorphism in endometriosis.

Estrogen plays a role in the pathogenesis of endometriosis. The CYP17 gene codes for the cytochrome P450c17alpha enzyme that is involved in the estrogen biosynthesis. We aimed to investigate if CYP17 polymorphism could be used as marker to predict the susceptibility of endometriosis. Women were divided into two groups: (1) severe endometriosis (n=119); (2) non-endometriosis groups (n=128). A 169-bp fragment encompassing the T/C polymorphic site in 5'-untranslated promoter region (5'-UTR) of the CYP17 was amplified by the polymerase chain reaction, treated with restriction enzyme MspA1I, and electrophoresis. The polymorphism was divided into restriction-enzyme indigestible (T homozygote), T/C heterozygote, and digestible (C homozygote). Genotypes and allelic frequencies for this polymorphism in both groups were compared. We observed a higher but non-significant percentage of T homozygote in the endometriosis women compared with the non-endometriosis women. Proportions of T homozygote / heterozygote / C homozygote for CYP17 in both groups were: (1) 26.1/46.2/27.7% and (2) 17.2/45.3/37.5% (p-value=0.131). T allele was related with higher susceptibility of endometriosis. T and C allele frequencies in both groups were: (1) 49.2/50.8%; (2) 39.8/60.2% (p-value=0.046). Despite the CYP17* T allele appearing to be associated with a trend of increased risk of endometriosis, CYP17 5'-UTR gene polymorphism might not be a useful marker for prediction of endometriosis susceptibility.

Elucidation of sialyltransferase as a tumour marker.

The report describes results of separation of sialyltransferase isoenzymes by electrofocusing plasma from healthy volunteers and patients having different types of malignant tumour. Extensive modification of the technique was adopted in determining enzyme activity, such as elution of gel strips with the buffer pH corresponding to the gel focusing point; assessment of the effect of different pH on endogenous incorporation of radioactivity to desialated fetuin; and quantitative analysis of protein present in each gel band for calculation of enzyme activity. Plasma from normal individuals showed the existence of 5 sialyltransferase isoenzymes at pI 4.8, 5.5, 6.3, 6.8 and 7.5. There were higher isoenzyme activities in plasma samples from patients afflicted with malignancy of lungs and colon in comparison to normal pattern. Endometrial and breast cancer patients also showed elevated levels of the enzyme which could be controlled by surgery and combined therapies with cytotoxic drugs and radiation, respectively. The observations suggest the potential use of sialyltransferase as a tool for tumour diagnosis, and are discussed in relation to prognosis of the disease in the course of therapy.