![]() ![]() The release of TSH is controlled by the tripeptide hormone TRH ( FIG. TSH, which is a pituitary-derived hormone that stimulates the thyroid gland to produce T 4 and T 3, is a non-covalently linked heterodimer glycoprotein that consists of α and β subunits. In this section, we provide a brief overview of the regulatory mechanism of the HPT axis and highlight the importance of local activation of thyroid hormone. In addition, we highlight the possible link between thyroid cancer and disrupted circadian machinery. Furthermore, we discuss the connection between disruptions of central and peripheral circadian pacemakers and thyroid function. We then summarize the current state of knowledge regarding the circadian regulation of the HPT axis. We first describe the regulatory mechanisms controlling the HPT axis and provide an overview of the circadian system. In this article, we review the interconnection between circadian clocks and thyroid function. Many endocrine factors are known to show time-dependent variations for example, TSH secretion exhibits a clear daily rhythmicity, and the HPT axis is under circadian control via the central circadian pacemaker in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus 9. Circadian disruption of the endocrine system is one of the main mechanisms that mediates these circadian-related adverse consequences 6– 8. Several lines of evidence indicate that chronic circadian disruption, which can be caused by shift work or travel across time zones, has long-term consequences on human health and increases the risk of weight gain, type 2 diabetes mellitus, cardiovascular disease and several types of cancer 4– 7. An approximately 24-h cell-autonomous circadian clock is present in virtually all cells of the body, and this circadian system tightly regulates physiological functions and endocrine rhythms 3. To better adapt to these cyclic environmental changes, organisms have evolved biological clocks. Organisms are exposed to various rhythmic events, such as daily and seasonal cycles. PT, pars tuberalis PN, pars intermediate PI, pars nervosa. This regulatory pathway is called the ‘hypothalamic–pituitary–thyroid axis’ 1, 2. T 3 derived from circulating T 4 regulates synthesis and release of TRH and pars distalis TSH as part of a negative feedback loop mediated by the thyroid hormone receptor. TSH induces most of the essential events in thyroid hormone production. TSH stimulates the thyroid gland to produce thyroid hormones (predominantly the prohormone T 4) via the TSH receptor on the thyroid follicle cell membrane. TRH stimulates thyrotrophs to synthesize TSH in the pars distalis (PD) of the pituitary gland by upregulating mRNA levels of TSHA and TSHB. Thyrotropin-releasing hormone (TRH) produced in the paraventricular nucleus (PVN) is secreted from the median eminence (ME) and transported to the pituitary via the hypothalamus–hypophyseal portal system. Therefore, the characterization of the thyroid clock machinery might improve the preoperative diagnosis of thyroid cancer. Expression profiles of circadian clock genes are abnormal in well-differentiated thyroid cancer but not in the benign nodules or a healthy thyroid. Disruption of circadian rhythms has been recognized as a perturbation of the endocrine system and of cell cycle progression. ![]() Although the hypothalamic–pituitary–thyroid axis is under the control of the circadian clock via the suprachiasmatic nucleus pacemaker, daily TSH secretion profiles are disrupted in some patients with hypothyroidism and hyperthyroidism. ![]() Chronic circadian disruption caused by shift work, travel across time zones or irregular sleep-wake cycles has long-term consequences on our health and is an important lifestyle factor that contributes to the risk of obesity, type 2 diabetes mellitus and cancer. The circadian system regulates virtually all physiological processes, which are further modulated by changes in external environment, such as light exposure and timing of food intake. In mammals, the central circadian pacemaker, which is located in the hypothalamic suprachiasmatic nucleus, controls peripheral circadian clocks. Circadian rhythmicity is an approximately 24h cell-autonomous period driven by transcription–translation feedback loops of specific genes, which are referred to as ‘circadian clock genes’. ![]()
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