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 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:
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:
- Glucose from the ingested lactose or sucrose is absorbed in the intestine and the level of glucose in blood rises.
- Elevation of blood glucose concentration stimulates endocrine cells in the pancreas to release insulin.
- Insulin has the major effect of facilitating entry of glucose into many cells of the body - as a result, blood glucose levels fall.
- When the level of blood glucose falls sufficiently, the stimulus for insulin release disappears and insulin is no longer secreted.
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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