Two factors can increase or decrease the concentration of a hormone in the blood. One of these is the rate of hormone secretion into the blood. The second is the rate of removal of the hormone from the blood, which is called the metabolic clearance rate. This is usually expressed in terms of the number of milliliters of plasma cleared of the hormone per minute. To calculate this clearance rate, one measures (1) the rate of disappearance of the hormone from the plasma per minute and (2) the concentration of the hormone in each milliliter of plasma. Then, the metabolic clearance rate is calculated by the following formula:
Metabolic clearance rate = Rate of disappearance of hormone from the plasma/Concentration of hormone in each milliliter of plasma
The usual procedure for making this measurement is the following: A purified solution of the hormone to be measured is tagged with a radioactive substance. Then the radioactive hormone is infused at a constant rate into the blood stream until the radioactive concentration in the plasma becomes steady. At this time, the rate of disappearance of the radioactive hormone from the plasma equals the rate at which it is infused, which gives one the rate of disappearance. At the same time, the plasma concentration of the radioactive hormone is measured using a standard radioactive counting procedure. Then, using the formula just cited, the metabolic clearance rate is calculated.
Hormones are "cleared" from the plasma in several ways, including (1) metabolic destruction by the tissues, (2) binding with the tissues, (3) excretion by the liver into the bile, and (4) excretion by the kidneys into the urine. For certain hormones, a decreased metabolic clearance rate may cause an excessively high concentration of the hormone in the circulating body fluids. For instance, this occurs for several of the steroid hormones when the liver is diseased, because these hormones are conjugated mainly in the liver and then "cleared" into the bile.
Hormones are sometimes degraded at their target cells by enzymatic processes that cause endocytosis of the cell membrane hormone-receptor complex; the hormone is then metabolized in the cell, and the receptors are usually recycled back to the cell membrane.
Most of the peptide hormones and catecholamines are water soluble and circulate freely in the blood. They are usually degraded by enzymes in the blood and tissues and rapidly excreted by the kidneys and liver, thus remaining in the blood for only a short time. For example, the half-life of angiotensin II circulating in the blood is less than a minute.
Hormones that are bound to plasma proteins are cleared from the blood at much slower rates and may remain in the circulation for several hours or even days. The half-life of adrenal steroids in the circulation, for example, ranges between 20 and 100 minutes, whereas the half-life of the protein-bound thyroid hormones may be as long as 1 to 6 days.
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