Endocrine System > Hormones, Receptors and Control Systems

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:

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 the hypothalamic-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 (illustrated to the right) 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.

Another type of feedback is seen in endocrine systems that regulate concentrations of blood components such as glucose. Drink a glass of milk or eat a candy bar and the following (simplified) series of events will occur:

Numerous other examples of specific endocrine feedback circuits are presented in the sections on specific hormones or endocrine organs.

Hormone Profiles: Concentrations Over Time

One important consequence of the feedback controls that govern hormone concentrations and the fact that hormones have a limited lifespan or halflife is that most hormones are secreted in "pulses". The following graph depicts concentrations of luteinizing hormone in the blood of a female dog over a period of 8 hours, with samples collected every 15 minutes:

The pulsatile nature of luteinizing hormone secretion in this animal is evident. Luteinizing hormone is secreted from the anterior pituitary and critically involved in reproductive function; the frequency and amplitude of pulses are quite different at different stages of the reproductive cycle.

With reference to clinical endocrinology, examination of the graph should also demonstrate the caution necessary in interpreting endocrine data based on isolated samples.

A pulsatile pattern of secretion is seen for virtually all hormones, with variations in pulse characteristics that reflect specific physiologic states. In addition to the short-term pulses discussed here, longer-term temporal oscillations or endocrine rhythms are also commonly observed and undoubtedly important in both normal and pathologic states.

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