TY - JOUR
T1 - Neuroanatomical pathways for thyroid hormone feedback in the human hypothalamus
AU - Alkemade, Anneke
AU - Friesema, Edith C.
AU - Unmehopa, Unga A.
AU - Fabriek, Babs O.
AU - Kuiper, George G.
AU - Leonard, Jack L.
AU - Wiersinga, Wilmar M.
AU - Swaab, Dick F.
AU - Visser, Theo J.
AU - Fliers, Eric
PY - 2005
Y1 - 2005
N2 - Context: Recent findings point to an increasing number of hypothalamic proteins involved in the central regulation of thyroid hormone feedback. The functional neuroanatomy of these proteins in the human hypothalamus is largely unknown at present. Objective: The aim of this study was to report the distribution of type II and type III deiodinase (D2 and D3) as well as the recently identified T-3 transporter, monocarboxylate transporter 8 (MCT8), in the human hypothalamus. Design: The study included enzyme activity assays, immunocytochemical studies, and mRNA in situ hybridizations in postmortem human hypothalamus (n = 9). Results: D2 immunoreactivity is prominent in glial cells of the infundibular nucleus/median eminence, blood vessels, and cells lining the third ventricle. By contrast, both D3 and MCT8 are expressed by neurons of the paraventricular (PVN), supraoptic, and infundibular nucleus (IFN). In support of these immunocytochemical data, D2 and D3 enzyme activities are detectable in the mediobasal human hypothalamus. Combined D2, D3, MCT8, and thyroid hormone receptor immunohistochemistry and TRH mRNA in situ hybridization clearly showed that D3, MCT8, and thyroid hormone receptor isoforms are all expressed in TRH neurons of the PVN, whereas D2 is not. Conclusions and Implications: Based on these findings, we propose three possible routes for thyroid hormone feedback on TRH neurons in the human PVN: 1) local thyroid hormone uptake from the vascular compartment within the PVN, 2) thyroid hormone uptake from the cerebrospinal fluid in the third ventricle followed by transport to TRH neurons in the PVN or IFN neurons projecting to TRH neurons in the PVN, and 3) thyroid hormone sensing in the IFN of the mediobasal hypothalamus by neurons projecting to TRH neurons in the PVN
AB - Context: Recent findings point to an increasing number of hypothalamic proteins involved in the central regulation of thyroid hormone feedback. The functional neuroanatomy of these proteins in the human hypothalamus is largely unknown at present. Objective: The aim of this study was to report the distribution of type II and type III deiodinase (D2 and D3) as well as the recently identified T-3 transporter, monocarboxylate transporter 8 (MCT8), in the human hypothalamus. Design: The study included enzyme activity assays, immunocytochemical studies, and mRNA in situ hybridizations in postmortem human hypothalamus (n = 9). Results: D2 immunoreactivity is prominent in glial cells of the infundibular nucleus/median eminence, blood vessels, and cells lining the third ventricle. By contrast, both D3 and MCT8 are expressed by neurons of the paraventricular (PVN), supraoptic, and infundibular nucleus (IFN). In support of these immunocytochemical data, D2 and D3 enzyme activities are detectable in the mediobasal human hypothalamus. Combined D2, D3, MCT8, and thyroid hormone receptor immunohistochemistry and TRH mRNA in situ hybridization clearly showed that D3, MCT8, and thyroid hormone receptor isoforms are all expressed in TRH neurons of the PVN, whereas D2 is not. Conclusions and Implications: Based on these findings, we propose three possible routes for thyroid hormone feedback on TRH neurons in the human PVN: 1) local thyroid hormone uptake from the vascular compartment within the PVN, 2) thyroid hormone uptake from the cerebrospinal fluid in the third ventricle followed by transport to TRH neurons in the PVN or IFN neurons projecting to TRH neurons in the PVN, and 3) thyroid hormone sensing in the IFN of the mediobasal hypothalamus by neurons projecting to TRH neurons in the PVN
U2 - https://doi.org/10.1210/jc.2004-2567
DO - https://doi.org/10.1210/jc.2004-2567
M3 - Article
C2 - 15840737
SN - 0021-972X
VL - 90
SP - 4322
EP - 4334
JO - Journal of clinical endocrinology and metabolism
JF - Journal of clinical endocrinology and metabolism
IS - 7
ER -