Regulation of Thyroid Hormone Secretion

Thyroid Regulation

Image by BYU-Idaho Winter 2015

Regulation of thyroid hormone secretion begins at the hypothalamus (see the image above). Recall that the hypothalamus secretes the hormone thyrotropin-releasing hormone (TRH) into the hypothalamo hypophyseal portal system. TRH stimulates cells in the anterior pituitary to secrete the hormone thyroid-stimulating hormone (TSH). TSH then stimulates the thyroid gland to secrete thyroid hormones, Thyroxine (T4) and T3. Proper levels of thyroid hormones in the blood are regulated by a classic negative feedback system. If thyroxine and T3 levels are high, they feed back on the hypothalamus and the pituitary to decrease TSH release. At the level of the hypothalamus, the thyroid hormones inhibit TRH production. In the anterior pituitary, they reduce the number of TRH receptors and inhibit TSH synthesis. The overall effect is to reduce TSH levels, which in turn lowers thyroid hormone synthesis and release. If thyroid hormone levels are low the inhibition is removed and more TSH is secreted to stimulate production and release of more thyroid hormones. Since the thyroid hormones have long half-lives, their concentrations in the blood remain relatively constant and do not tend to fluctuate.

This diagram illustrates a negative feedback loop. It shows the general steps of a negative feedback loop at the center (imbalance, hormone release, correction, and negative feedback) using the example of the hormone cascade that regulates metabolic rate. The hypothalamus releases TRH in response to low metabolic rate and or low T three and T four concentrations in the blood (imbalance). This triggers TSH release by the pituitary (hormone release). The TSH travels to the thyroid where it triggers T three and T four release by the thyroid cells. T three and T four increase basal metabolic rate of the body cells and cause a rise in body temperature (the calorigenic effect). T three and T four then feed back to the hypothalamus and inhibits TRH and TSH release. If metabolic rate is high and or T three and T four concentrations are low, then the hypothalamus stops releasing TRH (negative feedback). As a result, the anterior pituitary will not release TSH and no T three or T four will be produced by the thyroid.

Negative Feedback Loop regulating Thyroid Hormone Levels.
Author: OpenStax License: License: [CC BY 3.0 (http://creativecommons.org/licenses/by/3.0)], via Wikimedia Commons
Link: https://books.byui.edu/-SAYi

Another level of control of thyroid hormone activity occurs at the level of the target tissues. T3 is much more biologically active than thyroxine. At the target tissue thyroxine can be deiodinated (one of the iodine is removed) to produce T3. The enzyme that removes the iodine is deiodinase. By increasing or decreasing the activity of deiodinase thyroid hormone activity can be modulated.

Another factor that can impact thyroid hormone secretion is caloric intake. If caloric intake is greatly elevated (particularly increased carbohydrate consumption), T3 levels go up and metabolism is increased. On the other hand, if caloric intake is drastically reduced as would happen during starvation or a strict diet, T3 levels decrease and metabolism goes down. These mechanisms are thought to be regulated at the level of the target tissues rather than in the thyroid gland, hence they are mediated by changes in the activity of the deiodinase enzyme.

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