Thyroid hormones in diabetes, cancer, and aging.

Benoit R Gauthier,Petra Isabel Lorenzo,Alejandro Sola‐García,María Ángeles Cáliz‐Molina,Nadia Cobo‐Vuilleumier,Vivian Capilla‐González,Alejandro Martin‐Montalvo

doi:10.1111/acel.13260

Benoit R Gauthier, Petra Isabel Lorenzo + Show 5 more

Open Access

https://doi.org/10.1111/acel.13260

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Journal: Aging Cell	Publication Date: Oct 13, 2020
Citations: 77	License type: CC BY 4.0

Affiliation: Instituto de Salud Carlos III, Universidad de Sevilla

Abstract

Thyroid function is central in the control of physiological and pathophysiological processes. Studies in animal models and human research have determined that thyroid hormones modulate cellular processes relevant for aging and for the majority of age-related diseases. While several studies have associated mild reductions on thyroid hormone function with exceptional longevity in animals and humans, alterations in thyroid hormones are serious medical conditions associated with unhealthy aging and premature death. Moreover, both hyperthyroidism and hypothyroidism have been associated with the development of certain types of diabetes and cancers, indicating a great complexity of the molecular mechanisms controlled by thyroid hormones. In this review, we describe the latest findings in thyroid hormone research in the field of aging, diabetes, and cancer, with a special focus on hepatocellular carcinomas. While aging studies indicate that the direct modulation of thyroid hormones is not a viable strategy to promote healthy aging or longevity and the development of thyromimetics is challenging due to inefficacy and potential toxicity, we argue that interventions based on the use of modulators of thyroid hormone function might provide therapeutic benefit in certain types of diabetes and cancers.

Highlights

Thyroid hormone (TH) production is a tightly regulated process controlled by a classic negative feedback loop involving the hypothalamus, the pituitary, and the thyroid, which has led to the common name hypothalamus–pituitary–thyroid axis (Figure 1).The thyrotropin-releasing hormone (TRH) is produced in the hypothalamus
As opposed to other experimental models of hypothyroidism (Hine et al, 2017; Umezu et al, 2020), we found that the PAX8 heterozygous mice faithfully recapitulate the phenotype of humans with hypothyroidism, including insulin resistance, increased white adipose tissue (WAT) mass, and increased triglyceride content in skeletal
As opposed to compelling research indicating the association of diabetes mellitus (DM) and thyroid dysfunction, which is supported by the well-described role of THs on glucose metabolism and insulin secretion, other studies have failed to link hypothyroidism to the development of type 2 DM (T2DM) (Ishay et al, 2009; Radaideh et al, 2004)

Summary

Introduction

Thyroid hormone (TH) production is a tightly regulated process controlled by a classic negative feedback loop involving the hypothalamus, the pituitary, and the thyroid, which has led to the common name hypothalamus–pituitary–thyroid axis (Figure 1).The thyrotropin-releasing hormone (TRH) is produced in the hypothalamus. The direct modulation of TH levels using PAX8 heterozygous knockout mice, which suffer a mild hypothyroidism due to a direct defect in the thyroid gland, while exhibiting normal circulating levels of α-GSU of pituitary hormones in adulthood, did not result in improved health span or longer life span.

Results

Conclusion