ZFIN ID: ZDB-PUB-140130-7
Embryonic exposure to excess thyroid hormone causes thyrotrope cell death
Tonyushkina, K.N., Shen, M.C., Ortiz-Toro, T., and Karlstrom, R.O.
Date: 2014
Source: J. Clin. Invest.   124(1): 321-327 (Journal)
Registered Authors: Karlstrom, Rolf
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Apoptosis*
  • Cell Differentiation
  • Congenital Hypothyroidism/metabolism
  • Congenital Hypothyroidism/pathology
  • Embryo, Nonmammalian/pathology
  • Feedback, Physiological
  • Female
  • Humans
  • Iodide Peroxidase/metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects/metabolism
  • Prenatal Exposure Delayed Effects/pathology
  • Thyroid Hormones/physiology*
  • Thyrotrophs/physiology*
  • Thyrotropin, beta Subunit/metabolism
  • Thyroxine/physiology*
  • Zebrafish
  • Zebrafish Proteins/metabolism
PubMed: 24316972 Full text @ J. Clin. Invest.
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ABSTRACT

Central congenital hypothyroidism (CCH) is more prevalent in children born to women with hyperthyroidism during pregnancy, suggesting a role for thyroid hormone (TH) in the development of central thyroid regulation. Using the zebrafish embryo as a model for thyroid axis development, we have characterized the ontogeny of negative feedback regulation of thyrotrope function and examined the effect of excess TH on thyrotrope development. We found that thyroid-stimulating hormone β subunit (tshb) and type 2 deiodinase (dio2) are coexpressed in zebrafish thyrotropes by 48 hours after fertilization and that TH-driven negative feedback regulation of tshb transcription appears in the thyroid axis by 96 hours after fertilization. Negative feedback regulation correlated with increased systemic TH levels from the developing thyroid follicles. We used a transgenic zebrafish that expresses GFP under the control of the tshb promoter to follow thyrotrope fates in vivo. Time-lapse imaging revealed that early exposure to elevated TH leads to thyrotrope cell death. Thyrotrope numbers slowly recovered following the removal of excess TH. These data demonstrate that transient TH exposure profoundly impacts the thyrotrope population during a critical period of pituitary development and may have long-term implications for the functional reserve of thyroid-stimulating hormone (TSH) production and the TSH set point later in life.

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