Discuss the role of negative feedback mechanism in thyroid production.

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The Thyroid Gland

The Thyroid and Its Hormones

The thyroid gland, which consists of two lobes, is located in front of the windpipe (i.e., trachea), just below the voice box (i.e., larynx). The gland produces two structurally related hormones, thyroxine (T4) and triiodothyronine (T3), that are iodinated derivatives of the amino acid tyrosine. Both hormones are collectively referred to as thyroid hormone. T4 constitutes approximately 90 percent of the hormone produced in the thyroid gland. However, T3 is a much more active hormone, and most of the T4 produced by the thyroid is converted into T3 in the liver and kidneys. Thyroid hormone in general serves to increase the metabolism of almost all body tissues. For example, thyroid hormone stimulates the production of certain proteins involved in heat generation in the body, a function that is essential for maintaining body temperature in cold climates. Moreover, thyroid hormone promotes several other metabolic processes involving carbohydrates, proteins, and lipids that help generate the energy required for the bodys functions. In addition to those metabolic effects, thyroid hormone plays an essential role in the development of the central nervous system during late fetal and early postnatal developmental stages. Furthermore, thyroid hormone exerts an effect similar to that of GH on normal bone growth and maturation. Finally, thyroid hormone is required for the normal development of teeth, skin, and hair follicles as well as for the functioning of the nervous, cardiovascular, and gastrointestinal systems.

In addition to thyroid hormone, certain cells (i.e., parafollicular C cells) in the thyroid gland produce calcitonin, a hormone that helps maintain normal calcium levels in the blood. Specifically, calcitonin lowers calcium levels in the blood by reducing the release of calcium from the bones; inhibiting the constant erosion of bones (i.e., bone resorption), which also releases calcium; and inhibiting the reabsorption of calcium in the kidneys. One of the most important features of the endocrine system is its regulation (control) by

negative feedback.

This means that the glands within the endocrine system that stimulate the

release of a hormone (for example, the pituitary) from another gland (for example, the thyroid) are eventually shut off, in a sense, so that too much hormone is not produced and a hormone imbalance is avoided.

Control of Endocrine Activity..

The physiologic effects of hormones depend largely on their concentration in blood and extracellular fluid. Almost inevitably, disease results when hormone concentrations are either too high or too low, and precise control over circulating concentrations of hormones is therefore crucial. The concentration of hormone as seen by target cells is determined by three factors: Rate of production: Synthesis and secretion of hormones are the most highly regulated aspect of endocrine control. Such control is mediated by positive and negative feedback circuits, as described below in more detail. Rate of delivery: An example of this effect is blood flow to a target organ or group of target cells - high blood flow delivers more hormone than low blood flow. Rate of degradation and elimination: Hormones, like all biomolecules, have characteristic rates of decay, and are metabolized and excreted from the body through several routes. Shutting off secretion of a hormone that has a very short halflife causes circulating hormone concentration to plummet, but if a hormone's biological halflife is long, effective concentrations persist for some time after secretion ceases.

Feedback Control of Hormone Production.

Feedback circuits are at the root of most control mechanisms in physiology, and are particularly prominent in the endocrine system. Instances of positive feedback certainly occur, but negative feedback is much more common.

Negative feedback is seen when the output of a pathway inhibits inputs to the pathway.
The heating system in your home is a simple negative feedback circuit. When the furnace produces enough heat to elevate temperature above the set point of the thermostat, the thermostat is triggered and shuts off the furnace (heat is feeding back negatively on the source of heat). When temperature drops back below the set point, negative feedback is gone, and the furnace comes back on.

Feedback loops

are used extensively to regulate secretion of hormones in

thehypothalamic-pituitary axis. An important example of a negative feedback loop is seen in control of thyroid hormone secretion. The thyroid hormones thyroxine and triiodothyronine ("T4 and T3") are synthesized and secreted by thyroid glands and affect metabolism throughout the body. The basic mechanisms for control in this system are: Neurons in the hypothalamus secrete thyroid releasing hormone (TRH), which stimulates cells in the anterior pituitary to secrete thyroid-stimulating hormone (TSH). TSH binds to receptors on epithelial cells in the thyroid gland, stimulating synthesis and secretion of thyroid hormones, which affect probably all cells in the body. When blood concentrations of thyroid hormones increase above a certain threshold, TRH-secreting neurons in the hypothalamus are inhibited and stop secreting TRH. This is an example of "negative feedback".

Inhibition of TRH secretion leads to shut-off of TSH secretion, which leads to shut-off of thyroid hormone secretion. As thyroid hormone levels decay below the threshold, negative feedback is relieved, TRH secretion starts again, leading to TSH secretion.

Serum concentrations of T4 and its biologically active form T3 are maintained in vivo in a narrow range by the ability of thyroid hormone (TH) to limit its own production by negative feedback at the hypothalamic TSHreleasing hormone (TRH) neuron and pituitary thyrotroph. This feedback is critically dependent upon the presence of normal TH receptors (TRs), which bind to the promoters of TRH and TSH subunit genes and regulate their expression. In the presence of its ligand, T3, TRs mediate ligand-dependent repression of the transcription of these genes, and in the absence of T3, the transcription rate is not simply returned to baseline, but ligand-independent activation is observed. Negative feedback acts to stabilize the controlled variable. The controlled variable is what your body is trying to keep constant - e.g. blood pressure, blood glucose level,core body temperature, etc.

The components of a negative feedback loop are:

1. Sensor: measures the actual value of the controlled variable 2. Integrator: compares the actual value with the built in "set point". If measured actual value does not equal set point value, the integrator issues commands to an effector. 3. Effector: produces a response and acts to bring controlled variable back towards set point value. 4. When

actual value: set point value, integrator turns off command signals to effector.

Turning on of the negative feedback loop leads to turning off - which is why its called negative feedback.