The Type 3 Deiodinase Is a Critical Determinant of Appropriate Thyroid Hormone Action in the Developing Testis

• DOI: 10.1210/en.2015-1910
• Publication Date: 2016-01-04T18:00:35Z
• Authors: M. Elena Martinez; Aldona Karaczyn; J. Patrizia Stohn; William T. Donnelly; Walburga Croteau; Robin P. Peeters; Valerie A. Galton; Douglas Forrest; Donald St. Germain; Arturo Hernandez
• Keywords: DIO2

Abstract Timely and appropriate levels of thyroid hormone (TH) signaling are necessary to ensure normal developmental outcomes in many tissues. Studies using pharmacological models altered TH status have revealed an influence these hormones on testis development size, but little is known about the role endogenous determinants action developing male gonads. Using a genetic approach, we demonstrate that type 3 deiodinase (D3), which inactivates protects tissues from undue action, key factor. D3 highly expressed testis, D3-deficient (D3KO) mice exhibit thyrotoxicosis cell proliferation arrest neonatal resulting approximately 75% reduction size. This accompanied by larger seminiferous tubules, impaired spermatogenesis, hormonal profile indicative primary hypogonadism. A deficiency receptor-α fully normalizes size adult gene expression D3KO mice, indicating effects mediated through this receptor. Similarly, deficiencies D2 or monocarboxylate transporter 8 partially rescue abnormalities gonadal axis featured mice. Our study highlights as important tissue coordinately converge identifies critical factor testicular protection thyrotoxicosis.