Low Thyroid Hormone Levels Disrupt Thyrotrope Development
| Autor: | Theresa Ortiz-Toro, Rolf O. Karlstrom, Ksenia Tonyushkina, Tibor Mascari, Stefanie Krug |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Thyroid Hormones endocrine system medicine.medical_specialty Embryo Nonmammalian Organogenesis Cell Count 030209 endocrinology & metabolism Thyrotropin beta Subunit Biology Animals Genetically Modified 03 medical and health sciences 0302 clinical medicine Endocrinology Thyrotropic cell Internal medicine Thyrotrophs Congenital Hypothyroidism medicine Animals Goitrogen Receptor Zebrafish Research Articles Regulation of gene expression Receptors Thyroid Hormone Thyroid Gene Expression Regulation Developmental Cell Differentiation Embryo biology.organism_classification 030104 developmental biology medicine.anatomical_structure Propylthiouracil Pituitary Gland Hormone |
| Zdroj: | Endocrinology. 158:2774-2782 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2016-1935 |
| Popis: | Low thyroid hormone (TH) conditions caused by a variety of prenatal 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) to block TH synthesis, and this led to an approximately 50% increase in thyrotrope numbers and an 8- to 10-fold increase in tshb mRNA abundance in 2-week-old larvae and 1-month-old juveniles. Thyrotrope numbers returned to normal 3 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. |
| Databáze: | OpenAIRE |
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