Research

research
No results

Effect of endocrine disruptors on thyroid hormone homeostasis

Environmental pollution is rapidly increasing the amount of substances known as endocrine disruptors, that potentially exert a disruptive effects on hormone homeostasis, including thyroid hormone (TH) economy. These among others include plastic additives, pesticides, veterinary products, and their effects can vary widely. 

Altered regulation of thyroid hormone economy under physiological and pathophysiological conditions

During development, the negative thyroid hormone (TH) feedback setting ("set-point") of the hypothalamo-pituitary-thyroid (HPT) axis is fixed for the entire life-span, but TH levels required for optimal tissue function vary in an age-dependent manner. However, the feedback regulation of the HPT axis is not able to adapt to this changing demand by changing the fixed set-point, that may contribute to age-dependent impairments of tissue function. Our aim is to investigate whether there are mechanisms that may contribute to age-dependent regulation of tissue-specific TH homeostasis despite the fixed set-point of the HPT axis.

Completed research support for the past ten years

                                     

Current research support

                                 

Mechanisms underlying tissue hypothyroidism in the brain during thyroxine substitution therapy

Our aim is to identify the basic cellular and molecular pathways that underlie the symptoms of hypothyroidism in a group of patients who respond poorly to thyroxine (T4) monotherapy. While the therapy is able to normalize the TSH of these patients, they still suffer from symptoms of tissue hypothyroidism that adversely affect cognitive function and regulation of energy homeostasis. 

Development of thyroid hormone gradients in the nervous system

It is known that thyroid hormone (TH) signalling is compartmentalized in the brain; glial cells are responsible for type 2 deiodinase (D2)-mediated TH activation, while neurons regulate their intracellular TH levels by type 3 deiodinase (D3) catalyzed inactivation. Little is known however on how TH are presented to neurons and how the active and inactive forms of TH are transported between cells and brain regions.