|ZFIN ID: ZDB-PUB-170701-10|
Low thyroid hormone levels disrupt thyrotrope development
Tonyushkina, K., Krug, S., Ortiz-Toro, T., Mascari, T., Karlstrom, R.
|Source:||Endocrinology 158(9): 2774-2782 (Journal)|
|Registered Authors:||Karlstrom, Rolf|
|PubMed:||28658938 Full text @ Endocrinology|
Tonyushkina, K., Krug, S., Ortiz-Toro, T., Mascari, T., Karlstrom, R. (2017) Low thyroid hormone levels disrupt thyrotrope development. Endocrinology. 158(9):2774-2782.
ABSTRACTLow 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.