Abstract
1. Hypophysiotropic thyrotropin-releasing hormone (TRH) is synthesized in the hypothalamic paraventricular nucleus (PVN) and transported to the median eminence (ME) where it enters the hypophyseal portal blood. TRH in the ME is situated exclusively in nerve terminals, whereas TRH in the PVN and septum is of extrinsic (nerve terminals) as well as intrinsic (perikarya) origin.
2. To determine the source and possible differential regulation of TRH release from these structures, we blocked TRH axonal delivery by i.c.v. administration of colchicine into the lateral cerebral ventricle of euthyroid or hypothyroid rats in doses of 7.5 μg or 7.5, 75 and 100 μg, respectively, two days prior to the evaluation of the TRH secretion from the PVN, ME and the septum in vitro.
3. In euthyroid rats a low dose of colchicine did not significantly affect plasma TSH. The secretory response to both ethanol in an isosmolar medium and a high K+ in the ME as well as the PVN explants was well preserved. However, colchicine treatment resulted in the significant increase of basal secretion of TRH from the PVN.
4. Hypothyroidism induced by 200 mg/l methimazole in drinking water for two weeks resulted in growth arrest, elevated plasma thyrotropin and decreased TRH content in the PVN and the ME. Colchicine partially decreased elevated plasma thyrotropin and increased the TRH content in the PVN and its basal release in vitro which was independent of extracellular Ca2+. Interestingly, a TRH release from the PVN could not be further stimulated either by K+ membrane depolarization or by ethanol. TRH responsiveness to the stimulation remained unaffected in the ME. The effect of colchicine on the septal TRH secretion was intermediate between the effect observed in the PVN and the ME.
5. In conclusion, the absence of a TRH secretory response to stimuli in the PVN after colchicine disruption of the microtubules and Golgi system suggests that stimulated TRH release observed from the PVN explants in vitro occurs from nerve terminals projecting to the PVN from other brain regions. The independence from extracellular calcium implies that TRH released under the non-stimulating conditions occurs most likely via the constitutive secretory pathway from dendrites and/or perikarya. Regulation of septal TRH is markedly different from the hypophysiotropic one.
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An erratum to this article is available at http://dx.doi.org/10.1007/s10571-005-8496-8.
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Alexander, K., Mária, N., Jana, K. et al. Colchicine Treatment Differently Affects Releasable Thyrotropin-Releasing Hormone (TRH) Pools in the Hypothalamic Paraventricular Nucleus (PVN) and the Median Eminence (ME). Cell Mol Neurobiol 25, 681–695 (2005). https://doi.org/10.1007/s10571-005-4008-0
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DOI: https://doi.org/10.1007/s10571-005-4008-0