Thyroid Disorders Affect Circulating TRAIL Levels

A circulating protein called TNF-related apoptosis-inducing ligand (TRAIL) might have a role in the regulation of body weight and metabolism. Interestingly, thyroid hormones seem to increase TRAIL tissue expression.

Compared to the other pro-apoptotic TNF family members, TRAIL has the unique ability to induce apoptosis preferentially in transformed cells, such as tumor cells, while it spares the normal ones. The discovery of this property has led to a current study of TRAIL as an anticancer therapy.

Scientists at the University of Trieste (Italy) and their colleagues selected a total of 39 euthyroid (CNT), 49 hyperthyroid (HYPER), and 28 hypothyroid (HYPO) patients consecutively over a period of 12 months (January 2013–January 2014) from the subjects referred to a endocrine service at a local hospital. Euthyroidism, hyperthyroidism, and hypothyroidism were defined biochemically. Hyperthyroid patients had lower thyroid-stimulating hormone (TSH) and higher free triiodothyronine (fT3) and free thyroxine (fT4), while hypothyroid patients had higher TSH and lower fT3 and fT4 values as compared to reference ranges.

The investigators measured TSH, fT3, fT4, thyroid antibody (TG-Ab), thyroid peroxidase antibody (TPO-Ab) by the Lumiphos 530 chemiluminescence tracer alkaline phosphatase assay (CLEIA) with a DxI 800 analyzer. Thyroid-stimulating hormone receptor antibodies (TSHr-Ab) were measured by enzyme-linked immunosorbent assay (ELISA).

The scientists found that at baseline, hyperthyroid patients displayed significantly higher levels of circulating TRAIL as compared to controls, while in hypothyroid patients the levels were significantly lower. After thyroid function restoration, TRAIL levels normalized in both groups. At baseline, there was a significant direct correlation between thyroid hormones and TRAIL, for fT3, for fT4, and a significant inverse correlation between TSH and TRAIL. The team also found that consistent with these findings, T3 and T4 stimulated TRAIL released from peripheral blood mononuclear cells in vitro.

The authors concluded that thyroid hormones are associated with TRAIL expression in vivo and stimulate TRAIL expression in vitro. In particular, given the overlap between the metabolic effects of thyroid hormones and TRAIL, their work suggests that TRAIL might be one of the molecules mediating thyroid hormone peripheral effects. The study was published on May 25, 2017, in the journal Clinical Biochemistry.

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