PUBLICATION
Low thyroid hormone levels disrupt thyrotrope development
- Authors
- Tonyushkina, K., Krug, S., Ortiz-Toro, T., Mascari, T., Karlstrom, R.
- ID
- ZDB-PUB-170701-10
- Date
- 2017
- Source
- Endocrinology 158(9): 2774-2782 (Journal)
- Registered Authors
- Karlstrom, Rolf
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Cell Count
- Cell Differentiation/drug effects
- Congenital Hypothyroidism/complications
- Congenital Hypothyroidism/embryology
- Congenital Hypothyroidism/genetics
- Congenital Hypothyroidism/pathology
- Embryo, Nonmammalian
- Gene Expression Regulation, Developmental/drug effects
- Organogenesis/drug effects
- Pituitary Gland/cytology
- Pituitary Gland/drug effects*
- Pituitary Gland/embryology*
- Pituitary Gland/pathology
- Propylthiouracil/pharmacology
- Receptors, Thyroid Hormone/genetics
- Receptors, Thyroid Hormone/metabolism
- Thyroid Hormones/pharmacology*
- Thyrotrophs/cytology
- Thyrotrophs/drug effects*
- Thyrotrophs/physiology
- Thyrotropin, beta Subunit/genetics
- Zebrafish/embryology
- Zebrafish/genetics
- PubMed
- 28658938 Full text @ Endocrinology
Citation
Tonyushkina, K., Krug, S., Ortiz-Toro, T., Mascari, T., Karlstrom, R. (2017) Low thyroid hormone levels disrupt thyrotrope development. Endocrinology. 158(9):2774-2782.
Abstract
Low thyroid hormone (TH) conditions caused by a variety of pre- and perinatal problems have been shown to alter postnatal regulatory thyrotropin (TSH) responsiveness to TH in humans and rodents. The mechanisms underlying this pituitary TH-resistance remain unknown. Here we use the evolutionarily conserved zebrafish model to examine the effects of low TH on thyrotrope development and function. Zebrafish were exposed to the goitrogen 6-propyl-2-thiouracil (PTU) in order to block TH synthesis and this led to an approximately 50% increase in thyrotrope numbers and a 8-10 fold increase in tshb mRNA abundance in 2 week old larvae and 1 month old juveniles. Thyrotrope numbers returned to normal three weeks after cessation of PTU treatment, demonstrating that these effects were reversible and revealing substantial plasticity in pituitary-thyroid axis regulation. Using a T4 challenge assay we found that development under low TH conditions did not affect the ability of T4 to suppress tshb mRNA levels despite the thyrotrope hyperplasia that resulted from temporary low TH conditions. Together, these studies show that low developmental TH levels can lead to changes in thyrotrope number and function, providing a possible cellular mechanism underlying elevated TSH levels seen in neonates with either permanent or transient congenital hypothyroidism.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping