Aberrant telomerase expression in the endometrium of infertile women with deep endometriosis.

BACKGROUND AND AIMS: Considering the complex cellular and molecular mechanisms involved in endometriosis formation and progression and the similarities concerning the association of endometriosis with tumorigenesis and metastasis, we hypothesized a possible relationship between telomerase and the development/progression of endometriosis. The present study aimed to evaluate the expression of telomerase in the endometrium and peritoneal endometriotic lesions from women with endometriosis and controls. METHODS: A case-control study was performed comprising 25 infertile women with endometriosis and 44 fertile women without endometriosis as controls. Samples of endometrium and endometriotic peritoneal lesions of the same patient were harvested in the late luteal phase of the cycle. The expression of hTERT and GAPDH genes was measured by mRNA using qRT-PCR based on TaqMan methodology. Student t test was used to compare the values between the groups; p >0.05 was accepted as statistically significant. RESULTS: The mean expression of hTERT in the endometriosis group was significantly high when compared to the control group (1.24 ± 4.67 vs. 0.31 ± 1.10, p = 0.026). When the expression of hTERT was compared in relation to disease stage, the group of moderate/severe endometriosis showed increased expression in relation to control group (2.59 ± 7.35 vs. 0.31 ± 1.10, p = 0.026). Regarding endometriotic peritoneal lesions, only one 1/25 expressed hTERT mRNA. This patient had deep endometriosis. CONCLUSIONS: There was an association between the expression of telomerase (hTERT mRNA) and the genesis and progression of endometriosis.

M-protein is down-regulated in cardiac hypertrophy driven by thyroid hormone in rats.

Although it is well known that the thyroid hormone (T3) is an important positive regulator of cardiac function over a short term and that it also promotes deleterious effects over a long term, the molecular mechanisms for such effects are not yet well understood. Because most alterations in cardiac function are associated with changes in sarcomeric machinery, the present work was undertaken to find novel sarcomeric hot spots driven by T3 in the heart. A microarray analysis indicated that the M-band is a major hot spot, and the structural sarcomeric gene coding for the M-protein is severely down-regulated by T3. Real-time quantitative PCR-based measurements confirmed that T3 (1, 5, 50, and 100 physiological doses for 2 days) sharply decreased the M-protein gene and protein expression in vivo in a dose-dependent manner. Furthermore, the M-protein gene expression was elevated 3.4-fold in hypothyroid rats. Accordingly, T3 was able to rapidly and strongly reduce the M-protein gene expression in neonatal cardiomyocytes. Deletions at the M-protein promoter and bioinformatics approach suggested an area responsive to T3, which was confirmed by chromatin immunoprecipitation assay. Functional assays in cultured neonatal cardiomyocytes revealed that depletion of M-protein (by small interfering RNA) drives a severe decrease in speed of contraction. Interestingly, mRNA and protein levels of other M-band components, myomesin and embryonic-heart myomesin, were not altered by T3. We concluded that the M-protein expression is strongly and rapidly repressed by T3 in cardiomyocytes, which represents an important aspect for the basis of T3-dependent sarcomeric deleterious effects in the heart.