Zhi Zhang 


Supervsiors: Peter Bisschop, Anita Boelen, Andries Kalsbeek & Eric Fliers

Thyroid hormone is essential for normal bone development and maintenance of bone mass in adulthood. Hypothyroidism during childhood causes growth retardation, delayed bone age and short stature, whereas hyperthyroidism accelerates skeletal development and also results in short stature due to premature closure of the growth plates. In adults, hyperthyroidism increases bone resorption and bone formation leading to high bone turnover osteoporosis and associated increased fracture risk.

Apart from the classic Hypothalamus-Pituitary-Thyroid gland (HPT) axis pathway for the effects of thyroid hormone on bone, in the literature there is also evidence of regulation of bone metabolism via the autonomic nervous system, especially its sympathetic branch. Previous work in our group has shown that triiodothyronine (T3) in the brain can modulate glucose production through a sympathetic pathway. Accordingly, we hypothesized that T3 may also regulate bone metabolism via this neural pathway from the hypothalamus via the autonomic nervous system to the bone.

To explore this hypothesis, we will investigate in animal studies whether the increased bone resorption and bone formation observed earlier during systemic thyrotoxicosis also occur during a "central thyrotoxicosis" while maintaining peripheral euthyroidism. In addition, we will study the metabolic effects of central T3 on sympathetic outflow.


Schematic of thyroid hormone effects on bone metabolism
The hypothesis to be studied is indicated by the green dashed line.