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In mammals, the D3 is highly expressed in the placenta and pregnant uterus ( 10– 14), fetal and neonatal tissues ( 15, 16) as well as in the developing and adult brain ( 17, 18). Whereas the type 1 and 2 deiodinases (D1 and D2, respectively) activate T 4 by converting it to T 3, the type 3 deiodinase (D3) can convert both T 4 and T 3 into inactive metabolites by removing an iodine atom from the inner ring of these molecules ( 6, 9). Systemic and intracellular TH concentrations are also regulated at a prereceptor level by the three selenodeiodinases, whose actions result either in the activation or inactivation of TH ( 6– 8). Given the pleiotropic and profound biological effects of TH, the proper regulation of the HPT axis is of great importance to numerous biological processes. Serum TH provide additional regulatory control by exerting negative feedback effects on the axis at both the pituitary and hypothalamic levels. TRH generated in the hypothalamus induces the secretion from the pituitary of TSH, which in turn stimulates the thyroid gland to release TH into the circulation. Their concentrations in the plasma are tightly regulated by the hypothalamic-pituitary-thyroid (HPT) axis. Two TH are secreted by the thyroid: T 4, which is considered to be a prohormone, and the more active hormone T 3. Their effects are predominantly exerted through their nuclear receptors, which, upon binding of TH, function as transcription factors to regulate gene expression ( 3– 5). IN VERTEBRATES, THYROID HORMONES (TH) are critical for normal development, growth, and metabolism ( 1, 2). In conclusion, the absence of D3 activity results in impaired clearance of T 3 and significant defects in the mechanisms regulating the thyroid axis at all levels: hypothalamus, pituitary, and thyroid. This is accompanied by significant weight loss and lethality in mutant animals.
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Finally, treatment with T 3 results in a serum T 3 level in D3KO mice that is much higher than that in wild-type mice. In addition, D3KO animals rendered severely hypothyroid fail to show the expected increase in prepro-TRH mRNA in the paraventricular nucleus of the hypothalamus. Furthermore, after induction of severe hypothyroidism by antithyroid treatment, the rise in serum TSH in D3KO mice is only 15% of that observed in wild-type mice.
![type 3 type 3](https://englishgrammarhere.com/wp-content/uploads/2019/12/If-Clause-Type-3-Conditional-Type-3.png)
Our results demonstrate that the thyroid and pituitary glands of D3KO mice do not respond appropriately to TSH and TRH stimulation, respectively. In this report we describe the results of additional studies designed to investigate the regulation of the thyroid axis in this unique animal model. We have recently observed that mice lacking D3 activity (D3KO mice) develop perinatal thyrotoxicosis followed in adulthood by a pattern of hormonal levels that is suggestive of central hypothyroidism. The type 3 deiodinase (D3) is a selenoenzyme that inactivates thyroid hormones and is highly expressed during development and in the adult central nervous system.