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17-beta estradiol involved in down-regulation of TRAIL, CV health
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Blood concentrations of tumor necrosis factor-related apoptosis-inducing ligand, or TRAIL, appear to be inversely related to levels of 17-beta estradiol, according to recent study data.
These findings suggest that 17-beta estradiol may play a role in the down-regulation of circulating TRAIL, which is thought to act as an anticancer molecule, and also may reduce mortality in cardiovascular disease.
“In consideration of the protective role of TRAIL on the cardiovascular system, it will be interesting to evaluate whether a decrease of TRAIL circulating levels by 17-beta estradiol might explain the results of randomized clinical trials showing an unfavorable balance of benefits and risks for many women undergoing menopausal [hormone therapy] with 17-beta estradiol, especially for women in which HT was administered more than 10 years after the onset of menopause,” the researchers wrote. “We propose that circulating TRAIL might represent an important biomarker for risk stratification of cardiovascular disease in postmenopausal women undergoing HT.”
The researchers evaluated blood samples from two groups of participants. The first was a healthy subgroup (n=246) of age- and gender-stratified individuals from a previous prospective study. The second group consisted of women seen at the Institute for Maternal and Child Health, IRCCS Burlo Garofolo, of Trieste, Italy, and the Menopause and Osteoporosis Centre of the University of Ferrara.
This group (n=180) consisted of girls and women spanning a wide age range and representing a wide spectrum of 17-beta estradiol statuses (childhood, pregnancy, perimenopause, gonadotropin treatment). The researchers analyzed the serum and plasma samples for circulating TRAIL levels using enzyme-linked immunosorbent assay.
The researchers found that in women younger than 50 years, TRAIL plasma levels were significantly lower than those in age-matched men, whereas women aged at least 50 years had TRAIL levels that were significantly higher than those of age-matched men and the younger women. In addition, an evaluation of women with different hormonal conditions yielded a significant inverse relationship between blood concentrations of TRAIL and 17-beta estradiol. This inverse relationship was strongest in pregnant women, who had the lowest levels of TRAIL, and weakest in children and menopausal women, who had the highest levels of TRAIL. In women undergoing hormone treatments to assist reproduction, marked increases in 17-beta estradiol were accompanied by acute decreases in serum TRAIL concentration. Similarly, in vitro therapy with 17-beta estradiol was found to inhibit the expression of TRAIL in surrounding blood cells.
The researchers said these findings may serve to elucidate the potential risks and benefits of 17-beta estradiol HT in postmenopausal women.
Disclosure: The researchers report no relevant financial disclosures.
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