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Neuroanatomical pathways for thyroid hormone feedback in the human hypothalamus
Anneke Alkemade1, Edith C Friesema, Unga A Unmehopa
1Department of Endocrinology and Metabolism, Academic Medical Center of the University of Amsterdam, P.O. Box 22700, 1100 DE, Amsterdam, The Netherlands.
The Journal of Clinical Endocrinology and Metabolism
|April 21, 2005
Summary
This study maps thyroid hormone deiodinases (D2, D3) and transporter (MCT8) in the human hypothalamus. Findings reveal D3 and MCT8 in TRH neurons, suggesting local feedback mechanisms for thyroid hormone regulation.
Area of Science:
- Neuroendocrinology
- Molecular Endocrinology
Background:
- The human hypothalamus regulates thyroid hormone feedback.
- The precise distribution of key proteins like deiodinases and transporters in the human hypothalamus is largely unknown.
Purpose of the Study:
- To map the distribution of type II and type III deiodinase (D2 and D3) and monocarboxylate transporter 8 (MCT8) in the human hypothalamus.
- To understand the neuroanatomical basis of thyroid hormone feedback regulation in the human hypothalamus.
Main Methods:
- Enzyme activity assays.
- Immunocytochemical studies.
- mRNA in situ hybridization on postmortem human hypothalamus samples (n=9).
Main Results:
- D2 immunoreactivity was observed in glial cells, blood vessels, and third ventricle lining.
- D3 and MCT8 were expressed in neurons of the paraventricular nucleus (PVN), supraoptic nucleus, and infundibular nucleus (IFN).
- D3, MCT8, and thyroid hormone receptors were found in TRH neurons of the PVN, but D2 was absent.
Conclusions:
- Three potential pathways for thyroid hormone feedback on human PVN TRH neurons are proposed.
- These include local vascular uptake, cerebrospinal fluid transport, and indirect sensing via projecting neurons.
- The findings highlight the complex local regulation of thyroid hormone feedback within the human hypothalamus.