ESPEYB21 3. Thyroid Hypothalamus-Pituitary-Axis Regulation (2 abstracts)
3.3. TSH pulses finely tune thyroid hormone release and TSH receptor transduction
Anne Guillou , Yasmine Kemkem , Chrystel Lafont , Pierre Fontanaud , Davide Calebiro , Pauline Campos , Xavier Bonnefont , Tatiana Fiordelisio-Coll , Ying Wang , Emilie Brûlé , Daniel J Bernard , Paul Le Tissier , Frederik Steyn & Patrice Mollard
Endocrinology. 2023 Nov 20;165(1):bqad164. doi: 10.1210/endocr/bqad164. PMID: 37934802
Brief Summary: This study examined the pulsatile secretion of TSH and its regulatory role in thyroid hormone (TH) synthesis in mice. Using a novel ultra-sensitive ELISA for mouse TSH, it shows that TSH pulsatility plays a critical role in regulating thyroid function.
In addition to mapping the normal TSH secretion pattern in healthy mice, and the secretion pattern in a mouse model of disease (mouse made hypothyroid by an iodine-deficient diet enriched with propylthiouracil), experiments show that repeated short bursts of TSH secretion (ultradian pulses) are more effective in stimulating TH hormone production than sustained increases in TSH levels. Additional experiments investigating the role of TSH in thyroid follicle signal transduction, particularly via cAMP, finds that ultradian TSH pulses produce stepwise increases in intracellular cAMP, enhancing thyroid function. In contrast, continuous TSH stimulation leads to an initial cAMP rise, which then declines over time, suggesting that thyroid cells respond better to pulsatile TSH patterns.
This study highlights the importance of TSH pulsatility in thyroid function regulation, showing that TSH pulses are more effective than sustained increases in stimulating TH production. The experimental framework developed here will not only allow studying thyroid sensing of TSH secretion patterns in relation to the kinetics of signal transduction downstream of the TSH receptor, as the authors suggest, but may also be used to gain more insight in the precise causes of decreased TH synthesis/secretion in central congenital hypothyroidism (CH), by using mouse models expressing targeted mutations in IGSF1 or other genes associated with central CH like TBL1X or IRS4 [1]. In 2016, Joustra et al reported that patients with central CH due to IGSF1 deficiency showed decreased pulsatile secretion of TSH with decreased disorderliness and reduced diurnal variation. This however, was investigated in only three patients [2].
References: 1. Lauffer P, Zwaveling-Soonawala N, Naafs JC, Boelen A, van Trotsenburg ASP. Diagnosis and Management of Central Congenital Hypothyroidism. Front Endocrinol (Lausanne). 2021 Sep 9;12:686317. doi: 10.3389/fendo.2021.686317. eCollection 2021. PMID: 345668852. Joustra SD, Roelfsema F, Endert E, Ballieux BE, van Trotsenburg AS, Fliers E, Corssmit EP, Bernard DJ, Oostdijk W, Wit JM, Pereira AM, Biermasz NR. Pituitary Hormone Secretion Profiles in IGSF1 Deficiency Syndrome. Neuroendocrinology. 2016;103(3-4):408-16. doi: 10.1159/000439433. Epub 2015 Aug 25. PMID: 26336917
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ESPE Yearbook of Paediatric Endocrinology
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