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cholesterol profile. In males, the body mistakes the synthetic steroids for the natural hormone and lowers its own production of testosterone — as Ben Johnson found out. Infertility may result.

Growth Hormone

Some athletes take human growth hormone (HGH) preparations to supplement the effects of steroids, because HGH enlarges muscles, as steroids strengthen them. HGH has been available thanks to recombinant DNA technology (a type of genetic engineering) since 1985, and it is prescribed to treat children with certain forms of inherited dwarfism. However, HGH is available from other nations and can be obtained illegally to enhance athletic performance. Unlike steroids, HGH has a half-life of only 17 to 45 minutes, which means that it becomes unde-tectable in body fluids within an hour. There was no urine or blood test for it at the 2000 Olympics.

Boosting the Blood's

Oxygen-Carrying

Capacity

Red blood cells carry oxygen to muscles. Therefore, increasing the number of red blood cells can, theoretically, increase oxygen delivery to muscles and thereby enhance endurance. Swedish athletes introduced a practice called "blood doping" in 1972. The athletes would have blood removed a month of more prior to performance, then have the blood reinfused, boosting the red blood cell supply. Today's hightech version of blood doping is to take erythropoietin (EPO), which is a hormone secreted from the kidneys that signals the bone marrow to produce more red blood cells. Like human growth hormone, EPO is manufactured using recombinant DNA technology. It is used legitimately to treat certain forms of anemia.

Using EPO to improve athletic performance is ill advised. In 1987, it led to heart attacks and death in more than two dozen cyclists from the Netherlands. Runners and swimmers also use EPO. In the 2000 summer Olympic games, some athletes tried a different way to boost their red blood cell supplies—an experimental preparation of cow hemoglobin.

Almost as interesting as the ways in which some athletes seek to manipulate the endocrine system is the ways in which they seek to escape detection. For example, in the 2000 Olympics, some athletes used a water-soluble steroid compound that is metabolized much faster than testosterone, so it doesn't leave a trace. But officials were quick to respond, instituting a test to determine the ratio of testosterone to the impostor, epitestosterone.

An athlete can time drug use based on understanding how the body metabolizes a particular substance. For example, Irish swimmer Michelle Smith won 4 medals in the 1996 Atlanta Olympics, and passed all drug tests. But some months later, a random urine test for another competition showed a superlethal level of alcohol—which she had presumably added to the urine sample to disguise banned drugs. She was banned from the 2000 games. Similarly, East German athletes took home 216 medals in the 1976 and 1980 Olympics combined, but in 1978, between games, they admitted to steroid use in all sports except sailing!

Some caught athletes offer creative explanations for their altered personal biochemistries. A Latvian rower claimed he'd taken an herbal supplement, and not steroids, as did a U.S. shot-putter. A German runner claimed a competitor had spiked his toothpaste with steroids. And a track coach from Uzbekistan said that his athletes used growth hormone to treat hair loss. ■

parathyroid glands; norepinephrine and epinephrine from the adrenal glands; calcitonin from the thyroid gland; and glucagon from the pancreas.

Certain nonsteroid hormones employ second messengers other than cAMP. For example, a second messenger called diacylglycerol (DAG), like cAMP, activates a protein kinase leading to a cellular response.

In another mechanism, a hormone binding to its receptor increases calcium ion concentration within the target cell. Such a hormone may stimulate transport of calcium ions inward through the cell membrane or induce release of calcium ions from cellular storage sites via a second messenger called inositol triphosphate (IP3). The calcium ions combine with the protein calmodulin

(see chapter 9, p. 315), altering its molecular structure in a way that activates the molecule. Activated calmodulin can then interact with enzymes, altering their activities and thus eliciting diverse responses.

Still another hormonal mechanism uses cyclic guanosine monophosphate (cyclic GMP, or cGMP). Like cAMP, cGMP is a nucleotide derivative and functions in much the same manner as a second messenger.

Cellular response to a steroid hormone is directly proportional to the number of hormone-receptor complexes that form. In contrast, response to a hormone operating through a second messenger is greatly amplified. This is possible because many second messenger molecules can be activated in response to just a few hormone-receptor complexes. Because of such amplification, cells are highly sensitive to changes in the concentrations of nonsteroid hormones.

99 How does a steroid hormone act on its target cells? ^9 How does a nonsteroid hormone act on its target cells? ^9 What is a second messenger?

Prostaglandins

Prostaglandins are paracrine substances, acting locally, that are very potent and present in very small quantities. They are not stored in cells but are synthesized just before they are released. They are rapidly inactivated.

Some prostaglandins regulate cellular responses to hormones. For example, different prostaglandins can either activate or inactivate adenylate cyclase in cell membranes, thereby controlling production of cAMP and altering the cell's response to a hormone.

Prostaglandins produce a variety of effects. Some prostaglandins can relax smooth muscle in the airways of the lungs and in the blood vessels, dilating these passageways. Yet other prostaglandins can contract smooth muscle in the walls of the uterus, causing menstrual cramps and labor contractions. They stimulate secretion of hormones from the adrenal cortex and inhibit secretion of hydrochloric acid from the wall of the stomach. Prostaglandins also influence movements of sodium ions and water in the kidneys, help regulate blood pressure, and have powerful effects on both male and female reproductive physiology. When tissues are injured, prostaglandins promote inflammation (see chapter 16, p. 660).

Understanding prostaglandin function has medical applications. Drugs such as aspirin and certain steroids that relieve the joint pain of rheumatoid arthritis inhibit production of prostaglandins in the synovial fluid of affected joints. Daily doses of aspirin may reduce the risk of heart attack by altering prostaglandin activity. Prostaglandins may be used as drugs to dilate constricted blood vessels to relieve hypertension.

What are prostaglandins?

Describe one possible function of prostaglandins. What kinds of effects do prostaglandins produce?

Control of Hormonal ions

Hormones are continually excreted in the urine and broken down by various enzymes, primarily in the liver. Therefore, increasing or decreasing blood levels of a hor mone requires increased or decreased secretion. Hormone secretion is precisely regulated.

Control Sources

Hormone secretion must be precisely controlled so that these biochemicals can effectively maintain the internal environment. Control of hormone secretion occurs in three ways:

• The hypothalamus controls the anterior pituitary gland's release of tropic hormones, which are hormones that stimulate other endocrine glands to release hormones. The hypothalamus constantly receives information about the internal environment from neural connections and cerebrospinal fluid, made possible by its location near the thalamus and the third ventricle (fig. 13.7).

• Another group of glands responds directly to changes in the composition of the internal environment. For example, when the blood glucose level rises, the pancreas secretes insulin, and when the blood glucose level falls, it secretes glucagon, as we shall see later in the chapter in the section titled "Hormones of the Islets of Langerhans."

• The nervous system stimulates some glands directly. The adrenal medulla, for example, secretes its hormones (epinephrine and norepinephrine) in response to preganglionic sympathetic nerve impulses. The secretory cells replace the postganglionic sympathetic neurons, which would normally secrete norepinephrine alone as a neurotransmitter.

Negative Feedback Systems

Commonly, negative feedback systems control hormonal secretions (see chapter 1, p. 8). In such a system, an endocrine gland or the system controlling it is sensitive to the concentration of a substance the gland secretes or to the concentration of a product from a process it controls. Whenever this concentration reaches a certain level, the endocrine gland is inhibited (a negative effect), and its secretory activity decreases (fig. 13.8). Then, as the concentration of the gland's hormone decreases, the concentration of the regulated substance or process decreases too, and the inhibition of the gland is diminished. When the gland is less inhibited, it increases secretion of its hormone again. Such negative feedback systems maintain the concentrations of hormones (fig. 13.9).

99 How does the nervous system help regulate hormonal secretions?

Q What is a feedback system?

B How does a negative feedback system control hormonal secretion?

Nervous System Feedback Inhibition

Figure 13.7

The pituitary gland is attached to the hypothalamus and lies in the sella turcica of the sphenoid bone.

Figure 13.7

The pituitary gland is attached to the hypothalamus and lies in the sella turcica of the sphenoid bone.

Hormone A

Hormone A

Hormone A stimulates secretion of gland B

Hormone B

Hormone B inhibits secretion of gland A

Target

Hormone B has N organ action on target cells

Hormone B

Addition to bloodstream

Stimulation

Inhibition

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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