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Hypothalamic thyroid hormone feedback in health and disease
Eric Fliers1, Anneke Alkemade, Wilmar M Wiersinga
1Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. e.fliers@amc.uva.nl
Progress in Brain Research
|August 1, 2006
Summary
The human hypothalamus regulates thyroid hormone levels during illness. Key proteins like deiodinases and transporters in the hypothalamus modulate thyroid hormone action, influencing the hypothalamus-pituitary-thyroid axis setpoint.
Area of Science:
- Neuroendocrinology
- Thyroid hormone regulation
- Hypothalamic function
Background:
- The human hypothalamus's role in the neuroendocrine response to illness is under active investigation.
- Critical illness significantly alters the hypothalamus-pituitary-thyroid (HPT) axis, notably decreasing active triiodothyronine (T3) levels.
- Decreased thyrotropin-releasing hormone (TRH) mRNA in the paraventricular nucleus (PVN) suggests altered HPT axis setpoint regulation during illness and depression.
Purpose of the Study:
- To investigate the distribution and expression of key proteins involved in central thyroid hormone metabolism within the human hypothalamus.
- To elucidate the mechanisms underlying thyroid hormone action and regulation in the hypothalamus, particularly in the context of HPT axis setpoint changes.
Main Methods:
- Utilized immunocytochemistry, mRNA in situ hybridization, and enzyme activity assays to study thyroid hormone receptor (TR) isoforms, deiodinases (D2, D3), and monocarboxylate transporter 8 (MCT8) in the human hypothalamus.
- Examined protein and mRNA expression in specific hypothalamic regions, including the paraventricular nucleus (PVN) and mediobasal hypothalamus.
Main Results:
- Both D2 and D3 enzyme activities were detected in the mediobasal hypothalamus.
- D2 was prominent in glial cells and tanycytes, while D3, MCT8, and TRs were expressed by TRH neurons in the PVN.
- A model is proposed where glial cells convert thyroxine (T4) to T3 (via D2), which is then transported to TRH neurons for action or degradation (via D3).
Conclusions:
- The human hypothalamus plays a critical role in regulating thyroid hormone levels through localized metabolism and transport.
- Specific hypothalamic cell types and proteins (D2, D3, MCT8, TRs) are integral to modulating thyroid hormone availability and action at the TRH neuron level.
- This localized thyroid hormone system in the hypothalamus likely contributes to the adaptive changes observed in the HPT axis during critical illness and other conditions.