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Tupper Research Institute and Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Tufts-New England Medical Center (C.F., P.S.S., S.S., R.M.L.), and Departments of Community Health (W.M.R.) and Neuroscience (R.M.L.), Tufts University School of Medicine, Boston, Massachusetts 02111; and Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences (C.F.), Budapest H-1083, Hungary
Address all correspondence and requests for reprints to: Dr. Ronald M. Lechan, Division of Endocrinology, Box 268, Tufts-New England Medical Center, 750 Washington Street, Boston, Massachusetts 02111. E-mail: rlechan{at}tufts-nemc.org.
The nonthyroidal illness syndrome associated with fasting, infection, and chronic illness is characterized by low thyroid hormone levels and low or inappropriately normal TSH levels in circulating blood and reduced synthesis of TRH in hypophysiotropic neurons residing in the hypothalamic paraventricular nucleus (PVN). To test the hypothesis that ascending brainstem pathways are involved in mediation of bacterial lipopolysaccharide (LPS)-induced suppression of TRH mRNA in the PVN, we unilaterally transected brainstem pathways to the PVN and determined the effects of LPS on TRH gene expression and, as a control, on CRH gene expression in hypophysiotropic neurons using semiquantitative in situ hybridization histochemistry. The efficacy of the transection was determined by immunocytochemical detection of ascending adrenergic pathways in the PVN. In vehicle-treated animals, CRH mRNA in the PVN showed a significant reduction on the transected side compared with the intact side, whereas a significant increase in TRH mRNA was observed on the transected side compared with the intact side. After LPS administration (250 µg/100 g body weight), a dramatic increase in CRH mRNA was observed on the intact side, and a significantly lesser increase was found on the transected side. In contrast, LPS treatment resulted in reduction in TRH mRNA on the transected side compared with the intact side and a significant reduction in TRH mRNA on the transected side compared with vehicle-treated animals. These studies confirm an important role of ascending brainstem projections in LPS-induced activation of CRH gene expression, but indicate that they do not mediate the effect of LPS to inhibit hypophysiotropic TRH gene expression.
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