Hormone Secretion After a Stimulus and Duration of Action of Different Hormones. Some hormones, such as norepinephrine and epinephrine, are secreted within seconds after the gland is stimulated and may develop full action within another few seconds to minutes; the actions of other hormones, such as thyroxine or growth hormone, may require months for full effect. Thus, each of the different hormones has its own characteristic onset and duration of action—each tailored to perform its specific control function.

Concentrations of Hormones in the Circulating Blood and Hormonal Secretion Rates. The concentrations of hormones required to control most metabolic and endocrine functions are incredibly small. Their concentrations in the blood range from as little as 1 picogram (which is one millionth of one millionth of a gram) in each milliliter of blood up to at most a few micrograms (a few millionths of a gram) per milliliter of blood. Similarly, the rates of secretion of the various hormones are extremely small, usually measured in micrograms or milligrams per day. We shall see later in this chapter that highly specialized mechanisms are available in the target tissues that allow even these minute quantities of hormones to exert powerful control over the physiological systems.

FEEDBACK CONTROL OF HORMONE SECRETION

 Negative Feedback Prevents Overactivity of Hormone Systems. Although the plasma concentrations of many hormones fluctuate in response to various stimuli that occur throughout the day, all hormones studied thus far appear to be closely controlled. In most instances, this control is exerted through negative feedback mechanisms  that ensure a proper level of hormone activity at the target tissue. After a stimulus causes release of the hormone, conditions or products resulting from the action of the hormone tend to suppress its further release. In other words, the hormone (or one of its products) has a negative feedback effect to prevent oversecretion of the hormone or overactivity at the target tissue.

The controlled variable is sometimes not the secretory rate of the hormone but the degree of activity of the target tissue. Therefore, only when the target tissue activity rises to an appropriate level will feedback signals to the endocrine gland become powerful enough to slow further secretion of the hormone. Feedback regulation of hormones can occur at all levels, including gene transcription and translation steps involved in the synthesis of hormones and steps involved in processing hormones or releasing stored hormones.

Surges of Hormones Can Occur With Positive Feedback. In a few instances, positive feedback occurs when the biological action of the hormone causes additional secretion of the hormone. One example of positive feedback is the surge of luteinizing hormone (LH) that occurs as a result of the stimulatory effect of estrogen on the anterior pituitary before ovulation. The secreted LH then acts on the ovaries to stimulate additional secretion of estrogen, which in turn causes more secretion of LH. Eventually, LH reaches an appropriate concentration and typical negative feedback control of hormone secretion is then exerted.

Cyclical Variations Occur in Hormone Release. Super imposed on the negative and positive feedback control of hormone secretion are periodic variations in hormone release that are influenced by seasonal changes, various stages of development and aging, the diurnal (daily) cycle, and sleep. For example, the secretion of growth hormone is markedly increased during the early period of sleep but is reduced during the later stages of sleep. In many cases, these cyclical variations in hormone secretion are due to changes in activity of neural pathways involved in con trolling hormone release.

TRANSPORT OF HORMONES IN THE BLOOD

Water-soluble hormones (peptides and catecholamines) are dissolved in the plasma and transported from their sites of synthesis to target tissues, where they diffuse out of the capillaries, into the interstitial fluid, and ultimately to target cells.

Steroid and thyroid hormones, in contrast, circulate in the blood while being mainly bound to plasma proteins. Usually less than 10 percent of steroid or thyroid hormones in the plasma exist free in solution. For example, more than 99 percent of the thyroxine in the blood is bound to plasma proteins. However, protein bound hormones cannot easily diffuse across the capillaries and gain access to their target cells and are therefore biologically inactive until they dissociate from plasma proteins.

The relatively large amounts of hormones bound to proteins serve as reservoirs, replenishing the concentration of free hormones when they are bound to target receptors or lost from the circulation. Binding of hormones to plasma proteins greatly slows their clearance from the plasma.

“Clearance” of Hormones From the Blood. Two factors can increase or decrease the concentration of a hormone in the blood. One factor 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 and 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 (e.g., nanograms per minute) and (2) the plasma concentration of the hormone (e.g., nanograms per milliliter of plasma). Then, the metabolic clearance rate is calculated with use of the following formula:

Metabolic clearance rate

 = Rate of disappearance of hormone from the plasma/Concentration of hormone

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 con centration 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 phenomenon 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 hormonereceptor 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.