Decreased neuropeptide Y (NPY) expression in the infundibular nucleus of patients with nonthyroidal illness.
In patients with a variety of illnesses, serum concentrations of T3 decrease without giving rise to elevated serum levels of TSH, a phenomenon known as the sick euthyroid syndrome or nonthyroidal illness (NTI). Our previous studies in postmortem brain material showed decreased thyrotropin-releasing hormone (TRH) messenger RNA (mRNA) in the paraventricular nucleus (PVN) of patients with NTI, suggesting a role for TRH cells in the persistence of low TSH levels in NTI. In the present study, we hypothesized that changes in neuropeptide Y (NPY) input from the infundibular nucleus (IFN) to TRH cells in the PVN might be a determinant of decreased TRH expression in NTI. We investigated the hypothalamus of nine patients whose endocrine status had been assessed in a serum sample taken less than 24h before death and we examined NPY expression in the IFN by means of immunocytochemistry and mRNA in situ hybridization using an image analysis system. There was a negative correlation (r = -0.88; p = 0.01) between serum leptin concentrations and total NPY mRNA in the IFN. The total amount of NPY immunoreactivity in the IFN correlated with total NPY mRNA (r = 0.69; p = 0.04). In contrast to the situation in food-deprived rodents, total NPY immunoreactivity in the IFN showed a positive correlation with total TRH mRNA in the PVN (r = 0.77; p = 0.02). The results suggest a role for decreased NPY input from the IFN in the resetting of thyroid hormone feedback on hypothalamic TRH cells in NTI.
Fliers
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Department of Endocrinology and Metabolism, Academic Medical Center of the University of Amsterdam, 1100 DE, Amsterdam, The Netherlands. e.fliers@amc.uva.nl
Unmehopa
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UA
Manniesing
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Vuijst
C L
CL
Wiersinga
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WM
Swaab
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D005246:Feedback; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020738:Leptin / Q000097:blood; D008297:Male; D009478:Neuropeptide Y / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood*; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism
D020738:Leptin; D009478:Neuropeptide Y; D012333:RNA, Messenger; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin