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Dual signal transduction pathways activated by TSH receptors in rat primary tanycyte cultures

Matei Bolborea1, Gisela Helfer2, Francis J P Ebling2

  • 1Rowett Institute of Nutrition and Health University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, UK School of Life Sciences University of Nottingham Medical School, Nottingham NG7 2UH, UK Rowett Institute of Nutrition and Health University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, UK School of Life Sciences University of Nottingham Medical School, Nottingham NG7 2UH, UK.

Journal of Molecular Endocrinology
|April 17, 2015
PubMed

Insights

Thyroid-stimulating hormone (TSH) activates signaling pathways in tanycytes, influencing hypothalamic functions. TSH increases cyclic AMP (cAMP) and activates ERK1/2 phosphorylation, impacting gene expression and metabolic regulation.

Area of Science:

  • Neuroendocrinology
  • Hypothalamic Physiology
  • Cellular Signaling

Background:

  • Tanycytes are crucial hypothalamic cells involved in nutrient sensing, neurosecretion, and seasonal physiological adaptations.
  • Photoperiod-regulated thyroid-stimulating hormone (TSH) secretion from the pars tuberalis influences tanycytes via TSH receptors, mediating seasonal reproductive and metabolic changes.

Purpose of the Study:

  • To elucidate the specific signal transduction pathway utilized by TSH in tanycytes.
  • To understand how TSH binding to its receptor initiates intracellular responses within tanycytes.

Main Methods:

  • In situ hybridization confirmed TSH receptor expression in rat tanycytes.
  • Primary ependymal cell cultures, characterized as tanycytes, were used for functional assays.
  • ELISA, Western blot analysis, and RT-PCR measured changes in cAMP, ERK1/2 phosphorylation, and Dio2 mRNA expression following TSH treatment.

Main Results:

  • TSH treatment (100 IU/l) significantly increased intracellular cAMP levels in cultured tanycytes.
  • TSH also induced a cAMP-independent increase in ERK1/2 phosphorylation.
  • TSH stimulation led to a 2.17-fold increase in the expression of Dio2 mRNA.

Conclusions:

  • TSH signal transduction in tanycytes involves activation of the Gαs protein to elevate cAMP levels.
  • An alternative G protein-coupled pathway mediates the TSH-induced phosphorylation of ERK1/2.
  • These pathways collectively contribute to TSH-mediated regulation of gene expression and hypothalamic function in tanycytes.
Keywords:
median eminenceneuroendocrinepars tuberalisthyrotrophin

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