HPT axis‑independent TSHβ splice variant regulates the synthesis of thyroid hormone in mice

Liu,Chunrong; Miao,Jun; Liu,Xiaorong; Zhao,Zhankao; Kou,Tianlei; Liu,Jing; Wang,Ruimin; Li,Lanying; Dong,Qian

doi:10.3892/mmr.2019.10082

HPT axis‑independent TSHβ splice variant regulates the synthesis of thyroid hormone in mice

Authors:
- Chunrong Liu
- Jun Miao
- Xiaorong Liu
- Zhankao Zhao
- Tianlei Kou
- Jing Liu
- Ruimin Wang
- Lanying Li
- Qian Dong
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Affiliations: Department of Pathology, Affiliated Hospital of Logistics University of Chinese People's Armed Police Force, Tianjin 300162, P.R. China, Department of Spinal Surgery, Tianjin Hospital, Tianjin 300211, P.R. China, Department of Pathology, 66336 Millitary Hospital, Gaobeidian, Hebei 074000, P.R. China, Clinical Laboratory, Affiliated Hospital of Logistics University of Chinese People's Armed Police Force, Tianjin 300162, P.R. China, Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, P.R. China
Published online on: March 22, 2019 https://doi.org/10.3892/mmr.2019.10082
Pages: 4514-4522

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Abstract

Thyroid stimulating hormone (TSH) consists of an α‑subunit and a unique β‑subunit. The first in‑frame TSHβ splice variant produced by the cells of immune system was identified in 2009. The TSHβ splice variant and native TSHβ exhibit different expression profiles, and research has been conducted to elucidate the role of the TSHβ splice variant in different diseases. However, understanding of the fundamental physiological characteristics of the TSHβ splice variant is currently limited. To verify whether the TSHβ splice variant has the potential to induce thyroid follicular cells to synthesize thyroid hormone, in vivo and in vitro stimulation experiments were conducted in the present study. A total of 60 C57BL/6 mice were divided into control‑, 5 and 10 µg TSHβ splice variant‑treated groups at random. Mice were sacrificed at 0.5, 1 and 4 h after intraperitoneal injection, and serum levels of tri‑iodothyronine (T3) and thyroxine (T4) were determined using a radioimmunoassay. Thyroid follicular cells were isolated from the thyroids of mice, and stimulated with 2 µg/ml TSHβ splice variant. Supernatants were collected, and the levels of T3 and T4 were detected. The protein expression levels of the sodium‑iodide symporter, thyroperoxidase and thyroglobulin in thyroid follicular cells were quantified using western blot analysis. To verify whether the TSHβ splice variant expression was regulated by the hypothalamus‑pituitary‑thyroid (HPT) axis, similar to native TSHβ, a total of 60 C57BL/6 mice were equally divided into control, 2 mg/kg T3 intraperitoneal injection and 0.05 mg/kg thyroid‑releasing hormone intraperitoneal injection groups at random. Mice were sacrificed at 1 and 4 h after injection. Alterations in the expression of the TSHβ splice variant in the pituitary, thyroid, peripheral blood leukocytes and spleen tissues were detected using western blot analysis. The present study demonstrated that the TSHβ splice variant is not regulated by the HPT axis and may affect thyroid hormone synthesis. Modifications in the expression of the TSHβ splice variant may occur in a uniquely regulated manner to provide peripheral immunological compartments with a source of activated cells, particularly under immune stress.

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