Top corner save!!!

Brian Rowe Last Second Jedi Save - UCLA Soccer 2011 Final Four

Neuromuscular junctions and neurotransmitters

Neuromuscular junction

Whereas neurons communicate with other neurons at synapses, an alpha-motor neuron communicates with muscle fibers at a site known as a neuromuscular junction. The function of the neuromuscular junction is essentially the same as that of a synapse. In fact, the proximal part of the neuromuscular junction is the same: It starts with the axon terminals of the motor neuron, which release neurotransmitters into the space between the motor nerve and the muscle fiber in response to an action potential. However, in the neuromuscular junction, the axon terminals protrude into motor end plates, which are troughlike segments on the plasmalemma. Picture below shows.

The motor end plate is invaginated(folded to form cavities). The cavity thus formed is called the synaptic gutter. As with synapses, the space between the neuron and the muscle fiber is the synaptic cleft.

Neurotransmitters released from the alpha-motor neuron axon terminals diffuse across the synaptic cleft and bind to receptors on the muscle fiber’s plasmalemma. This binding typically causes depolarization by opening sodium ion channels, allowing more sodium to enter the muscle fiber. As always, if the depolarization reaches the threshold, an action potential is formed. It spreads across the plasmalemma into the T-tubules, inititating muscle fiber contraction. As in the neuron, the plasmalemma, once depolarized, must undergo repolarization. During the period of repolarization, the sodium gates are closed and the potassium gates are open; thus, like the neuron, the muscle fiber is unable to respond to any further stimulation. This period is reffered to as the refractory period. Once the electrical conditions of the muscle fiber are restored to resting levels, the fiber can respond to another stimulus. Thus, the refractory period limits the motor unit’s firing frequency.

Now we know how the impulse is transmitted between two cells. But to understand what happens once the impulse is transmitted, we must first examine the chemical signals that accomplish transmission.

Neurotransmitters

More than 50 neurotransmitters have been positively identified or are suspected as potential candidates. These can be cathegorized as either (a) small-molecule, rapid-acting neurotransmitters or (b) neuropeptide, slow-acting neurotransmitters. The small-molecule, rapid-acting transmitters, which are responsible for most neural transmissions, are our main concern.

Acetylholine and norepinephrine are the two major neurotransmitters involved in regulating our physiological responses to exercise. Acetylholine is the primary neurotransmitter for the motor neurons that innervate skeletal muscle and for most parasympathetic neurons. It is generally an excitatory neurotransmitter, but it can have inhibitory effects at some parasympathetic nerve endings, such as in the heart. Norepinephrine is the neurotransmitter for the most sympathetic neurons, and it too can be either excitatory or inhibitory, depending on the receptors involved.

Once the neurotransmitters binds to the post-synaptic receptor, the nerve impulse has been successfully transmitted. The neurotransmitter is then either degraded by enzymes, actively transported back into the presynaptic terminals for reuse, or diffused away from the synapse.

Synapse

For a neuron to communicate with another neuron, first in action potential must occur. Once the action potential occurs, it travels the full length of the axon, ultimately reaching the axon terminals. How does the action potential move from the neuron in which it starts to another neuron?

Neurons communicate with each other across synapses. A synapse is the site of action potential transmission from one neuron to another. There are both chemical and mechanical synapses, but the most common type is the chemical synapse, which is our focus. As seen in the figure up, a synapse between two neurons includes:

• The axon terminals of the neuron sending the action potential;
• Receptors on the neuron receiving the action potential, and
• The space between these structures.

The neuron sending the action potential across the synapse is called the presynaptic neuron, so axon terminals are presynaptic terminals. Similarly, the neuron receiving the action potential on the opposite side of the synapse is called the postsynaptic receptors. The axon terminals and postsynaptic receptors are not physically in contact with each other. A narrow gap, the synaptic cleft, separates them.

The action potential can be transmitted across a synapse in only one direction: from the axon terminals of the presynaptic neuron to the postsynaptic receptors, usually on the dendrites, of the postsynaptic neuron. Impulses also can go directly to receptors on the cell body: about 5% to 20% of the axon terminals are adjacent to the cell body instead of the dendrites. Why can the action potential go in only one direction?

The presynaptic terminals of the axon contain a large number of saclike structures, called synaptic vesicles. These sacs contain neurotransmitter chemicals. When the impulse reaches the presynaptic axon terminals, the synaptic vesicles respond by dumping their chemicals into the synaptic cleft. These neurotransmitters then diffuse across the synaptic cleft to the postsynaptic neuron’s receptors. The postsynaptic receptors bind the neurotransmitter once it diffuses across the synaptic cleft. When this binding occurs, the impulse has been transmitted successfully to the next neuron and can be transmitted onward.

Nerve impulse

A nerve impulse – an electrical charge – is the signal that passes from one neuron to the next and finally to an end organ, such as a group of muscle fibers, or back to the CNS. For simplicity, think of the nerve impulse traveling through a neuron much as electricity travels through the electrical impulse is generated and how it travels through a neuron.

Resting membrane potential

The cell membrane of a neuron at rest has a negative electrical potential of about -70mV. This means that if one were to insert a voltmeter probe inside the cell, the electrical charges found there and the charges found outside the cell would differ by 70mV, and the inside would be negative relative to the outside. This electrical potential difference is known as the resting membrane potential(RMP). It is caused by a separation of charges across the membrane differ, the membrane is said to be polarized.

The neuron has a high concentration of potassium ions(K⁺) on the inside of the membrane and a high concentration of sodium ions(Na⁺) on the outside. The imbalance in the number of ions inside and outside the cell causes the RMP. The imbalance in the number of ions inside and outside the cell causes the RMP. This imbalance is maintained in two ways. First, the cell membrane is much more permeable to K⁺ than to Na⁺, so the K⁺ can move more freely. Because ions tend to move to establish equilibrium, some of the K⁺ will move to an area where it is less concentrated, outside the cell. The Na⁺ cannot move to the inside as easily. Second, sodium-potassium pumps in the neuron membrane, which contain Na⁺-K⁺ adenosine triphosphatase(ATPase), maintain the imbalance on each side of the membrane by actively transporting potassium ions in the sodium ions out. The sodium-potassium pump moves three Na⁺ out of the cell for each two K⁺ it brings in. The end result is that more positively charged ions are outside the cell than inside, creating the potential difference across the membrane. Maintenance of a constant RMP of about -70mV is primarily a function of the sodium-potassium pump.

Depolarization and hyperpolarization

If the inside of the cell becomes less negative relative to the outside, the potential difference across the membrane decreases. The membrane will be less polarized. When this happens, the membrane is said to be depolarized. Thus, depolarization occurs any time the charge difference becomes less than the RMP of -70mV, moving closer to zero. This typically results from a change in the membrane’s Na⁺ permeability. 

The opposite can also occur. If the charge difference across the membrane increases, moving from the RMP to an even more negative value, then the membrane becomes more polarized. This is known as hyperpolarization. Changes in the membrane potential are actually signals used to receive, transmit, and integrate information within and between cells. These signals are of two types, graded potentials and action potentials. Both are electrical currents created by the movement of ions.

Graded potentials

Graded potentials are localized changes in the membrane potential. These changes can be either depolarizations or hyperpolarizations. The membrane contains ion channels with ion gates that act as doorways into and out of the neuron. These gates are usually closed, preventing ion flow; but they open with stimulation; allowing ions to move from the outside to the inside or vice versa. This ion flow alters the charge separation, changing the polarization of the membrane.

Graded potentials are triggered by a change in the neuron’s local environment. Depending on the location and type of neuron involved, the ion gates may open in response to the transmission of an impulse from another neuron or in response to sensory stimuli such as changes in chemical concentrations, temperature, or pressure.

Recall that most neuron receptors are located on the dendrites( although some are on the cell body), yet the impulse is always transmitted from the axon terminals at the opposite end of the cell. For a neuron to transmit an impulse, the impulse must travel almost the entire length of the neuron. Although a graded potential may result in depolarization of the entire cell membrane, it is usually just a local event such that the depolarization does not spread very far along the neuron. To travel the full distance, an impulse must generate an action potential.

Action potentials

An action potential is a rapid and substantial depolarization of the neuron’s membrane. It usually lasts about 1ms. Typically, the membrane potential changes from the RMP of about -70mV to a value of about +30mV and then rapidly returns to its resting value. This is illustrated in the picture below. How does this marked change in membrane potential occur?

All action potentials begin as graded potentials. When enough stimulation occurs to cause a depolarization of at least 15 to 20mV, an action potential results. In other words, if the membrane depolarizes from the RMP of -70mV to a value of -50 to -55mV, the cell will experience an action potential. The membrane voltage at which a graded potential becomes an action potential is called the depolarization threshold. Any depolarization that does not attain the threshold will not result in an action potential. For example, if the membrane potential changes from the RMP of -70mV to -60mV, the change is only 10mV and does not reach the threshold; thus, no action potential occurs. But any time depolarization reaches or exceeds the threshold, an action potential will result. This is the all-or-none principle.

When a given segment of an axon is generating an action potential and its sodium gates are open, it is unable to respond to another stimulus. This is reffered to as the absolute refractory period. When the sodium gates are closed, the potassium gates are open, and repolarizing is occurring, the segment of the axon can then respond to a new stimulus, but the stimulus must be of substantially greater magnitude to evoke an action potential. This is reffered to as the relative refractory period.

Propagation of the action potential

Now that we understand how a neural impulse, in the form of an action potential, is generated, we can look at how the impulse is propagated, or how it travels through the neuron. Two characteristics of the neuron become particularly important when we consider how quickly an impulse can pass through the axon: myelination and diameter.

Myelin sheath

The axons of many neurons, especially large neurons, are myelinated, meaning they are covered with a sheath formed by myelin, a fatty substance that insulates the cell membrane. This myelin sheath is formed by specialized cells called Schwann cells.

The sheath is not continuous. As it spans the length of the axon, the myelin sheath exhibits gaps between adjacent Schwann cells, leaving the axon uninsulated at those points. These gaps are reffered to as nodes of Ranvier. The action potential appears to jump from one node to the next as it transverses a myelinated fiber. This is reffered to as salutatory conduction, a much faster type of conduction than occurs in unmyelinated fibers.

Myelination of peripheral motor neurons occurs over the first several years of life, partly explaning why children need time to develop coordinated movement. Individuals affected by certain neurological diseases, such as MS as discussed in our chapter opening, experience degeneration of the myelin sheath and a subsequent loss of coordination.

Diameter of the neuron

The velocity of nerve impulse transmission is also determined by the neuron’s size. Neurons of larger diameter conduct nerve impulses faster than neurons of smaller diameter because larger neurons present less resistance to local current flow.

Overview of the nervous system

The nervous system as a whole is composed of two components: the central nervous system(CNS) and the peripheral nervous system(PNS). The CNS is composed of the brain and spinal cord, while the PNS is composed of two major divisions, the sensory division(or afferent division) and the motor division(or efferent division). The sensory division is responsible for informing the CNS about what is going on within and outside the body. The motor division is responsible for sending information from CNS to the various parts of the body in response to the signals coming in from the sensory division. The motor division is composed of two parts, the autonomic nervous system and the somatic nervous system. Under is the schema of these relationships.

Structure and function of the nervous system

The neuron is the structural unit of the nervous system. We first review the anatomy of the neuron and then look at how it functions – allowing electrical impulses to be transmitted throughout the body.

Neuron

Individual nerve fibers(nerve cells), depicted in the figure below, are called neurons. A typical neuron is composed of three regions:

• The cell body, or soma
• The dendrites
• The axon

The cell body contains the nucleus. Radiating out from the cell body are the cell processes; the dendrites and the axon. On the side toward the axon, the cell body tapers into a cone-shaped region region known as the axon hillock. The axon hillock has an important role in impulse conduction.

Most neurons contain many dendrites. These are the neuron’s receivers. Most impulses, or action potentials, coming into the neuron from sensory stimuli or from adjacent neurons typically enter the neuron via the dendrites. These processes then carry the impulses toward the cell body.

In contrast, most neurons have only one axon. The axon is the neuron’s transmitter and conducts impulses away from the cell body. Near its end, an axon splits into numerous end branches. The tips of these branches are dilated into tiny bulbs known as axon terminals or synaptic knobs. These terminals or knobs house numerous vesicles(sacs) filled with chemicals known as neurotransmitters that are used for communication between a neuron and another cell. The structure of the neuron allows nerve impulses to enter the neuron through the dendrites, and to a lesser extent through the cell body, and to travel through the cell body and axon hillock, down the axon, and out through the end branches to the axon terminals. We next explain in more detail how this happens, including how these impulses travel from one neuron to another and from a motor neuron to muscle fibers.  

Hormonal regulation of fluid and electrolyte balance during exercise

Fluid balance during exercise is critical for optimal metabolic, cardiovascular, and thermoregulatory function. At the onset of exercise, water is shifted from the plasma volume to the interstitial and intracellular spaces. This water shift is specific to the amount of muscle that is active and the intensity of effort. Metabolic by-products begin to accumulate in and around the muscle fibers, increasing the osmotic pressure there. Water is then drawn into these areas by diffusion. Also, increased muscular activity increases blood pressure, which in turn drives water out of the blood(hydrostatic forces). In addition, sweating increases during exercise. The combined effect of these actions is that the muscles and sweat glands gain water at the expense of plasma volume. For example, running at approximately 75% of VO₂max decreases plasma volume by 5% to 10% . Reduced plasma volume decreases blood pressure and the amount of blood flow to the skin and muscles. Both of these effects can impede athletic performance.

The endocrine system plays a major role in monitoring fluid levels and correcting imbalances, along with regulating electrolyte balance, especially that of sodium. The two major hormones involved in this regulation are antidiuretic hormone released from the posterior pituitary and aldosterone, a mineralocorticoid released from the adrenal cortex. The kidneys are the primary target organ for both of these hormones.

Posterior pituitary

The pituitary’s posterior lobe is an outgrowth of neural tissue form the hypothalamus. For this reason, it is also reffered to as the neurohypophysis. It secretes two hormones; antidiuretic hormone(ADH; also called vasopressin or arginine vasopressin) and oxytocin. Both of these hormones are actually produced in the hypothalamus. They travel through the neural tissue and are stored in vesicles within nerve endings in the posterior pituitary. These hormones are released into capillaries as needed in response to neural impulses from the hypothalamus.

Of the two posterior pituitary hormones, only ADH is known to play an important role during exercise. Antidiuretic hormone promotes water conservation by increasing the water permeability of the kidneys’ collecting ducts. As a result, less water is excreted in the urine, creating an “antidiuresis”.

Muscular activity and sweating cause electrolytes to become concentrated in the blood plasma. This is called hemoconcentration, and it increases the plasma osmolality(the ionic concentration of dissolved substances in the plasma). This is the primary physiological stimulus for ADH release. The increased osmolality is sensed by osmoreceptors in the hypothalamus. A second and related stimulus for ADH release is a low plasma volume. In response to either stimuli, the hypothalamus sends neural impulses to the posterior pituitary, stimulating ADH release. The ADH enters the blood, travels to the kidneys, and promotes water retention in an effort to dilute the plasma electrolyte concentration back to normal levels. This hormone’s role in conserving body water minimizes the extent of water loss and therefore the risk of severe dehydration during periods of heavy sweating and hard exercise. Picture below illustrates this process. 

Adrenal cortex revisited

The mineralocorticoids, secreted from the adrenal cortex, maintain electrolyte balance in the extracellular fluids, especially that of sodium(Na⁺) and potassium(K⁺). Aldosterone is the major mineralocorticoid, responsible for at least 95% of all mineralocorticoid activity. It works primarily by promoting renal reabsorption of sodium, thus causing the body to retain sodium. When sodium is retained, so is water: thus, aldosterone, like ADH, results in water retention. Sodium retention also enhances potassium excretion, so aldosterone plays a role in potassium balance as well. For these reasons, aldosterone secretion is stimulated by many factors, including decreased plasma sodium, decreased blood volume, decreased blood pressure, and increased plasma potassium concentration. 

Kidneys

Although the kidneys are not typically considered major endocrine organs, they release a hormone called erythropoetine. Erythropoetin(EPO) regulates red blood cell(erythrocyte) production by stimulating bone marrow cells. The red blood cells are essential for transporting oxygen to the tissues and removing carbon dioxide, so this hormone is extremely important in our adaptation to training and altitude. The kidneys also release renin, a hormone and enzyme involved in blood pressure control and fluid and electrolyte balance.

The kidneys have a strong regulatory influence on blood pressure that also allows them to regulate fluid balance. Plasma volume is a major determinant of blood pressure: when plasma volume decreases, so does blood pressure. Blood pressure is monitored by specialized cells within the kidneys. During exercise, these cells can be stimulated by decreased blood pressure, decreased blood flow to the kidneys through increased sympathetic nervous activity accompanying exercise, or direct stimulation from the sympathetic nerves.

Figure shows the mechanism involved in renal control of blood pressure, the renin-angiotensin-aldosterone mechanism. The kidneys respond to decreased blood pressure or blood flow by forming an enzyme and hormone called renin. Renin, in turn, converts a plasma protein called angiotensinogen into an active form called angiotensin I. In the blood, angiotensin I is converted to angiotensin II when it encounters the enzyme angiotensin converting enzyme(ACE) in the lungs. Angiotensin converting enzyme inhibitors are a class of drugs used in the treatment of high blood pressure. They lower blood pressure by blocking, or inhibiting, the conversion of angiotensin I to angiotensin II. Angiotensin II acts in two ways. First, it is a potent constrictor of blood vessels. Through this action, peripheral resistance increases, which raises the blood pressure. The second job of angiotensin II is to trigger aldosterone release from the adrenal cortex.

Recall that aldosterone’s primary action is to promote sodium reabsorption in the kidneys. Because water follows sodium, this renal conservation of sodium causes the kidneys to also retain water. The net effect is to conserve body’s fluid content, thereby minimizing the loss of plasma volume while keeping blood pressure near normal. Figure below illustrates the changes in plasma volume and aldosterone concentrations during 2h of exercise.

The hormonal influences of ADH and aldosterone persist for up to 12 to 48h after exercise, reducing urine production and protecting the body from further dehydration. In fact, aldosterone’s prolonged enhancement of Na⁺ reabsorption may cause the body’s Na⁺ concentration to increase above normal following an exercise bout.  

As shown in the figure on the right side, individuals who are subjected to three repeated days of exercise and dehydration show a significant increase in plasma volume that continues to increase throughout the period of activity. This increase in plasma volume appears to parallel the body’s retention of dietary Na⁺. When the daily bouts of activity are terminated, the excess Na⁺ and water are excreted in urine.

Most athletes involved in heavy training have an expanded plasma volume, which dilutes various blood constituents. The actual amount of proteins and electrolyte(solutes) within the blood remains unaltered, but the substances are dispersed throughout a greater volume of water(plasma), so they are diluted and their concentration decreases. This phenomenon is called hemodilution.

“Physiology of sport and exercise”, fourth edition; Jack H. Wilmore, David L. Costill, W. Larry Kenney

Hormonal regulation of metabolism during exercise

As noted earlier, carbohydrate and fat metabolism are responsible for maintaining muscle ATP levels during prolonged exercise. Various hormones work to ensure glucose and FFA availability for muscle energy metabolism. In the next two sections we examine how the metabolism of glucose and fat are affected by these hormones during exercise. Because carbohydrate is the primary fuel used during both  brief and prolonged exhaustive exercise, we first consider the hormones that regulate its availability.

Regulation of glucose metabolism during exercise

The heightened energy demands of exercise require that more glucose be made available to the muscles. Recall that glucose is stored in the body as glycogen, primarily in the muscles and the liver. Glucose must be freed from its storage form of glycogen, so glycogenolysis must increase. Glucose freed from the liver enters the blood to circulate throughout the body, allowing it access to active tissues. Plasma glucose concentration also can be increased through gluconeogenesis.

Regulation of plasma glucose concentration

Four hormones work to increase the amount of circulating plasma glucose:

• Glucagon
• Epinephrine
• Norepinephrine
• Cortisol

The plasma glucose concentration during exercise depends on a balance between glucose uptake by exercising muscles and its release by the liver. At rest, glucose release from the liver is facilitated by glucagon, which promotes both liver glycogen breakdown and glucose formation from amino acids. During exercise, glucagon secretion increases. Muscular activity also increases the rate of catecholamine release from the  adrenal medulla, and these hormones(epinephrine and norepinephrine) work with glucagons to further increase glycogenolysis. Cortisol concentrations also increase during exercise. Cortisol increases protein catabolism, freeing amino acids to be used within the liver for gluconeogenesis. Thus, all four of these hormones can increase plasma glucose by enhancing the processes of glycogenolysis(breakdown of glycogen) and gluconeogenesis(making glucose from other substrates). In addition to the effects of the four major glucose-controlling hormones, growth hormone increases mobilization of FFAs and decreases cellular uptake of glucose, so less glucose is used by the cells(more remains in circulation); and the thyroid hormones promote glucose catabolism and fat metabolism.

The amount of glucose released by the liver depends on exercise intensity and the duration. As intensity increases, so does the rate of catecholamine release. This can cause the liver to release more glucose than is being taken up by the active muscles. Consequently, during or shortly after an explosive, short-term sprint bout, blood glucose concentrations may be 40% to 50% above the resting level, illustrating that the glucose release by the liver is greater than the uptake by the muscles.

The greater the exercise intensity, the greater the catecholamine release, and thus the glycogenolysis rate is significantly increased. This process occurs not only in the liver but also in the muscle. The glucose released from the liver enters the blood to become available to the muscle. But the muscle has a more readily available source of glucose: its own glycogen. The muscle uses its own glycogen stores before using the plasma glucose during explosive, short-term exercise. Glucose released from the liver is not used as readily, so it remains in the circulation, elevating the plasma glucose. Following exercise, plasma glucose concentrations decrease as the glucose enters the muscle to replenish the depleted muscle glycogen stores.

During exercise bouts that last for several hours, however, the rate of liver glucose release more closely matches the muscles’ needs, keeping plasma glucose at or only slightly above the resting concentrations. As muscle uptake of glucose increases, the liver’s rate of glucose release also increases. In most cases, plasma glucose does not begin to decline until late in the activity as liver glycogen stores become depleted, at which time glucagons concentrations increase significantly. Glucagon and cortisol together enhance gluconeogenesis, providing more fuel.

Figure below illustrates the changes in plasma concentrations of epinephrine, norepinephrine, glucagon, cortisol, and glucose during 3h of cycling. Although the hormonal regulation of glucose remains intact throughout such longterm activities, the liver’s glycogen supply may become critically low. As a result, the liver’s rate of glucose release may be unable to keep pace with the muscles’ rate of glucose uptake. Under this condition, plasma glucose may decline despite strong hormonal stimulation. Glucose ingestion during the activity can play a major role in maintaining plasma glucose concentrations. 

Glucose uptake by muscle

Merely releasing sufficient amounts of glucose into the blood does not ensure that the muscle cells will have enough glucose to meet their energy demands. Not only must the glucose be released and delivered to these cells; it also must be taken up by the cells. Transport of glucose through the cell membranes and into muscle glucose through the cell membranes and into muscle cells in controlled by insulin. Once glucose is delivered to the muscle, insulin facilitates its transport into the fibers.

Surprisingly, as seen in figure below, plasma insulin concentration tends to decrease during prolonged submaximal exercise, despite a slight increase in plasma glucose concentration and glucose uptake by muscle. This apparent contradiction between the plasma insulin concentrations and the muscles’ need for glucose serves as a reminder that a hormone’s activity is determined not only by its concentration in the blood but also by a cell’s sensitivity to that hormone. Exercise may enhance insulin’s binding to receptors on the muscle fiber, thereby reducing the need for high concentrations of plasma insulin to transport glucose across the muscle cell membrane into the cell. This is important, because during exercise four hormones are trying to release glucose from its storage sites and create new glucose. High insulin concentrations would oppose their action, preventing this needed increase in plasma glucose supply. 

Regulation of fat metabolism during exercise

Although fat generally contributes less than carbohydrate to muscles’ energy needs during exercise, mobilization and oxidation of FFAs are critical to performance in endurance exercise. During such prolonged activity, carbohydrate reserves become depleted, and muscle must rely more heavily on the oxidation of fat for energy production. When carbohydrate reserves are low(low plasma glucose and low muscle glycogen), the endocrine system can accelerate the oxidation of fats(lypolysis), thus ensuring that muscles’ energy needs can be met.

Free fatty acids are stored as triglycerides in fat cells and inside muscle fibers. Adipose tissue triglycerides, however, must be broken down to release the FFAs, which are then transported to the muscle fibers. The rate of FFA uptake by active muscle correlates highly with the plasma FFA concentration. Increasing this concentration would increase cellular uptake of the FFA. The rate of triglyceride breakdown may determine, in part, the rate at which muscles use fat as a fuel source during exercise.

The rate of lypolysis is controlled by at least five hormones:

• (decreased) Insulin
• Epinephrine
• Norepinephrine
• Cortisol
• Growth hormone

The major factor responsible for adipose tissue lypolysis during exercise is a fall in circulating insulin. Lipolysis is also enhanced through the elevation of epinephrine and norepinephrine. In addition to having a role in gluconeogenesis, cortisol accelerates the mobilization and use of FFAs for energy during exercise. Plasma cortisol concentration peaks after 30 to 45 min of exercise and then decreases to near-normal levels. But the plasma FFA concentration continues to increase throughout the activity, meaning that lipase continues to be activated by other hormones. The hormones that continue this process are the catecholamines and growth hormone. The thyroid hormones also contribute to the mobilization and metabolism of FFAs, but to a much lesser degree.

Thus, the endocrine system plays a critical role in regulating ATP production during exercise as well as controlling the balance between carbohydrate and fat metabolism.

“Physiology of sport and exercise”, fourth edition; Jack H. Wilmore, David L. Costill, W. Larry Kenney

Hormonal response to acute exercise and change in response with exercise training

Schema will be following: HORMONE – RESPONSE TO ACUTE EXERCISE(UNTRAINED) – EFFECT OF EXERCISE TRAINING

Anterior pituitary gland

Growth hormone(GH) – increases with increasing rates of work – attenuated response at the same rate of work

Thyrotropin(TSH) – increases with increasing rates of work – no known effect

Adrenocorticotropin(ACTH) – increases with increasing rates of work and duration – attenuated response at same rate of work

Prolactin – increases with exercise – no known effect

Follicle-stimulating hormone(FSH) – small or no change – no known effect

Luteinizing hormone(LH) – small or no change – no known effect

Posterior pituitary

Antidiuretic hormone(ADH or vasopressin) – increases with increasing rates of work – attenuated response at same rate of work

Oxytocin – unknown – unknown

Thyroid

Thyroxine(T₄) and triiodothyronine(T₃) – free T₃ and T₄ increase with increasing rates of work – increased turnover of T₃ and T₄ at same rate of work

Calcitonin – unknown – unknown

Parathyroid

Parathyroid hormone(PTH or parathormone) – increases with prolonged exercise – unknown

Adrenal medulla

Epinephrine – increases with increasing rates of work, starting at about 75% of VO₂max – attenuated response at same rate of work

Norepinephrine – increases with increasing rates of work, starting at about 50% of VO₂max – attenuated response at same rate of work

Adrenal cortex

Aldosterone – increases with increasing rates of work – unchanged

Cortisol – increases only at high rates of work – slightly higher values

Pancreas

Insulin – decreases with increasing rates of work – attenuated response at same rate of work

Glucagon – increases with increasing rates of work – attenuated response at same rate of work

Kidney

Renin – increases with increasing rates of work – unchanged

Erythropoetin(EPO) – unknown – unchanged

Testes

Testosterone – small increases with exercise – resting level decreases in male runners

Ovaries

Estrogens and progesterone – small increases with exercise – resting levels might be decreased in highly trained women

“Physiology of sport and exercise”, fourth edition; Jack H. Wilmore, David L. Costill, W. Larry Kenney

Endocrine glands and their hormones – overview

Anterior pituitary gland

The pituitary gland is a marble-sized gland at the base of the brain. The secretory action of the pituitary is controlled by either neural mechanisms or hormones secreted by the hypothalamus. Therefore, the pituitary gland can be thought of as the relay between central nervous system control centers and peripheral endocrine glands.

The pituitary gland is composed of three lobes: anterior, intermediate and posterior. The intermediate lobe is very small and is thought to play little or no role in humans, but both the posterior and anterior lobes have major endocrine functions. The anterior pituitary has a major role in fluid and electrolyte balance.

The anterior pituitary, also called the adenohypophysis, secretes six hormones in response to releasing factors and inhibiting factors(hormones) secreted by the hypothalamus. Communication between the hypothalamus and the anterior lobe of the pituitary occurs through a specialized circulatory system that transports the releasing and inhibiting factor from the hypothalamus to the anterior pituitary. The major functions of each of the anterior pituitary hormones, along with their releasing and inhibiting factors are discussed here. Exercise appears to be a strong stimulant to the hypothalamus because exercise increases the release rate of all anterior pituitary hormones.

Of the six anterior pituitary hormones, four are tropic hormones, meaning they affect the functioning of other endocrine glands. The exceptions are growth hormone and prolactin. Growth hormone is a potent anabolic agent(a substance that promotes constructive metabolism). It promotes muscle growth and hypertrophy by facilitating amino acid transport into the cells. In addition, growth hormone directly stimulates fat metabolism(lypolysis) by increasing the synthesis of enzymes involved in this process. Growth hormone concentrations are elevated during aerobic exercise, apparently in proportion to the exercise intensity, and typically remain elevated for some time after exercise.

Thyroid gland

The thyroid gland is located along the midline of the neck, immediately below the larynx. It secretes two important nonsteroid hormones, triiodothyronine(T₃) and thyroxine(T₄), which regulate metabolism in general, and an additional hormone, calcitonin, which assists in regulating calcium metabolism.

The two metabolic thyroid hormones share similar functions. Triiodothyronine and thyroxine increase the metabolic rate of almost all tissues and can increase the body’s basal metabolic rate by as much as 60% to 100%. These hormones also:

• Increase protin synthesis(also enzyme synthesis);
• Increase the size and number of mitochondria in most cells;
• Promote rapid cellular uptake of glucose;
• Enhance glycolysis and gluconeogenesis;
• Enhance lipid mobilization, increasing FFA availability for oxidation.

Release of thyrotropin(thyroid-stimulating hormone, or TSH) from the anterior pituitary increases during exercise. Thyroid-stimulating hormone controls the release of triiodothyronine and thyroxine, so the exercise-induced increase in TSH would be expected to stimulate the thyroid gland. Exercise does increase plasma thyroxine concentrations, but a delay occurs between the increase in TSH concentrations during exercise and the increase in TSH concentrations during exercise and the increase in plasma thyroxine concentration. Furthermore, during prolonged submaximal exercise, thyroxine concentrations remain relatively constant after a sharp initial increase as exercise begins, and triiodothyronine concentrations tend to decrease.

Adrenal glands

The adrenal glands are situated directly atop each kidney and are composed of the inner adrenal medulla and the outer adrenal cortex. The hormones secreted by these two parts are quite different, so we consider them separately. The adrenal medulla produces and releases two hormones, epinephrine and norepinephrine, which are collectively referred to as catecholamines. Because of its origin in the adrenal gland, a synonym for epinephrine is adrenaline. When the adrenal medulla is stimulated by the sympathetic nervous system, approximately 80% of its secretion is epinephrine and 20% is norepinephrine, although these percentages vary with different physiological conditions. The catecholamines have powerful effects similar to those of the sympathetic nervous system. Recall that these same catecholamines function as neurotransmitters in the sympathetic nervous system: however, the hormones’ effect last longer because these substances are removed from the blood relatively slowly compared to the quick reuptake and degradation of the neurotransmitters. These two hormones prepare a person for immediate action, often called the “fight-or-flight response”.

Although some of the specific actions of these two hormones differ, the two work together. Their combined effects include:

• Increased heart rate and force of concentration;
• Increased metabolic rate;
• Increased glycogenolysis(breakdown of glycogen to glucose) in the liver and muscle;
• Increased release of glucose and FFAs into the blood;
• Redistribution of blood to the skeletal muscles(through vasodilatation of vessels supplying skeletal muscles and vasoconstriction of vessels to the skin and viscera);
• Increased blood pressure;
• Increased respiration.

Release of epinephrine and norepinephrine is affected by a wide variety of factors, including changes in body position, psychological stress, and exercise. Plasma concentrations of these hormones increase as individuals gradually increase their exercise intensity. Plasma norepinephrine concentrations increase markedly at work rates above 50% of VO₂max, but epinephrine concentrations do not increase significantly until the exercise intensity exceeds 60% to 70% of VO₂max. During long-duration steady-state activity of moderate intensity, blood concentrations of both hormones increase. When the exercise bout ends, epinephrine returns to resting concentrations within only a few minutes of recovery, but norepinephrine can remain elevated for several hours.

The adrenal cortex secretes more than 30 different steroid hormones, referred to as corticosteroids. These generally are classified into three major types: mineralocorticoids, glucocorticoids, and gonadocorticoids(sex hormones).

The glucocorticoids are essential components in the ability to adapt to external changes and stress. They also help maintain fairly consistent plasma glucose concentrations even when we go for long periods without ingesting food. Cortisol, also known as hydrocortisone, is the major corticosteroid. It is responsible for about 95% of all glucocorticoid activity in the body. Cortisol:

• Stimulates gluconeogenesis to ensure an adequate fuel supply;
• Increases mobilization of FFAs, making them more available as an energy source;
• Decreases glucose utilization, sparing it for the brain;
• Stimulates protein catabolism to release amino acids for use in repair, enzyme synthesis, and energy production;
• Acts as an anti-inflammatory agent;
• Depresses immune reactions;
• Increases the vasoconstriction caused by epinephrine.

Pancreas

The pancreas is located behind and slightly below the stomach. Its two major hormones are insulin and glucagon. The balance of these two opposing hormones provides the major control of plasma glucose concentrations. When plasma glucose is elevated(hyperglycemia), as after a meal, the pancreas receives signals to release insulin into the blood.

Among its actions, insulin:

• Facilitates glucose transport into the cells, especially those in muscle;
• Promotes glycogenolysis;
• Inhibits gluconeogenesis.

Insulin’s main function is to reduce the amount of glucose circulating in the blood. But it is also involved in protein and fat metabolism, promoting cellular uptake of amino acids and enhancing synthesis of protein and fat.

The pancreas secretes glucagon when the plasma glucose concentration falls below normal concentrations(hypoglycemia). Its effects generally oppose those of insulin. Glucagon promotes increased breakdown of liver glycogen to glucose(glycogenolysis) and increased gluconeogenesis, both of which increase plasma glucose levels.

During exercise lasting 30 min or longer, the body attempts to maintain plasma glucose concentrations. However, insulin concentrations tend to decline. Research has shown that the ability of insulin to bind to its receptors on muscle cells increases during exercise,  due in large part to increased blood flow to muscle. This increases the body’s sensitivity to insulin and reduces the need to maintain high plasma insulin concentrations for transporting glucose into the muscle cells. Plasma glucagons, on the other hand, shows a gradual increase throughout exercise. Glucagon primarily maintains plasma glucose concentrations by stimulating liver glycogenolysis. This increases glucose availability to the cells, maintaining adequate plasma glucose concentrations to meet increased metabolic demands. The responses of these hormones are usually blunted in trained individuals, and those who are well trained are better able to maintain plasma glucose concentrations.

“Physiology of sport and exercise”, fourth edition; Jack H. Wilmore, David L. Costill, W. Larry Kenney

Hormones in human body - general info

Hormones are involved in most physiological processes, so their actions are relevant to many aspects of exercise and sport performance. A discussion of hormonal control is included cause hormones significantly affect metabolism. However, hormones play key roles in almost every system of the body. Here will be described general mechanisms by which hormones act and their chemical nature.

Chemical classification of hormones

Hormones can be categorized as two basic types: steroid hormones and nonsteroid hormones. Steroid hormones have a chemical structure similar to cholesterol, since most are derived from cholesterol. For this reason, they are soluble in lipids and diffuse rather easily through cell membranes. This group includes the hormones secreted by:

• The adrenal cortex(such as cortisol and aldosterone);
• The ovaries(estrogen and progesterone);
• The testes(testosterone), and
• The placenta(estrogen and progesterone).

Nonsteroid hormones are not lipid soluble, so they cannot easily cross cell membranes. The nonsteroid hormone group can be subdivided into two groups: protein or peptide chormones and amino acid-derived hormones. The two hormones from the thyroid gland(thyroxine and triiodothyronine) and the two from the adrenal medulla(epinephrine and norepinephrine) are amino acid hormones. All other nonsteroid hormones are protein or peptide hormones. 

Hormone actions

Because hormones travel in the blood, they contact virtually all body tissues. How, then, do they limit their effects to specific targets? This ability is attributable to the specific hormone receptors possessed by the target tissues. The interaction between the hormone and its specific receptor has been compared with a lock(receptor) and key(hormone) arrangement, in which only the correct key can unlock a given action within the cells. The combination of a hormone bound to its receptor is referred to as a hormone-receptor complex.

Each cell typically has from 2,000 to 10,000 receptors. Receptors for nonsteroid hormones are located  on the cell membrane, whereas those for steroid hormones are found either in the cell’s cytoplasm or in its nucleus. Each hormone is usually highly specific for a single type of receptor and binds only with its specific receptors, thus affecting only tissues that contain those specific receptors. Numerous mechanisms allow hormones to control the actions of cells.

As mentioned earlier, steroid hormones are lipid soluble and thus pass easily through the cell membrane. Their mechanism of action is illustrated below. Once inside the cell, a steroid hormone binds to its specific receptors. The hormone-receptor complex then enters the nucleus, binds to part of the cell’s DNA, and activates certain genes. This process is referred to as direct gene activation. In response to this activation, mRNA is synthesized within the nucleus. The mRNA then enters the cytoplasm and promotes protein synthesis. These proteins may be:

• Enzymes that can have numerous effects on cellular processes;
• Structural proteins to be used for tissue growth and repair;
• Regulatory proteins that can alter enzyme function.

Because nonsteroid hormones cannot cross the cell membrane, they react with specific receptors outside the cell, on the cell membrane. A nonsteroid hormone molecule binds to its receptor and triggers a series of enzymatic reactions that lead to the formation of an intracellular second messenger. A widely distributed second messenger that mediates a specific hormone-receptor response is cyclic adenosine monophosphate(cyclic AMP, or cAMP). This mechanism is illustrated in the picture below.

In this case, attachment of the hormone to the appropriate membrane receptor activates an enzyme, adenylate cyclase, situated within the cell membrane. This enzyme catalyzes the formation of cAMP from cellular ATP. Cyclic AMP then can produce specific physiological responses, which can include:

• Activation of cellular enzymes
• Change in membrane permeability
• Change in cellular metabolism
• Stimulation of cellular secretions.

Thus, nonsteroid hormones typically activate the cAMP system of the cell, which then alters intracellular functions.

Hormones are not secreted uniformly, but rather are released in relatively brief bursts, so plasma concentrations of specific hormones fluctuate over short periods such as an hour or less. But these concentrations also fluctuate over longer periods of time, showing daily or even monthly cycles(such as monthly menstrual cycles). How do endocrine glands know when to release their hormones?

Most hormone secretion is regulated by a negative feedback system. Secretion of a hormone causes some change in the body, and this change in turn inhibits further hormone secretion. Consider how a home thermostat works. When the room temperature decreases below some preset level, the thermostat signals the furnace to produce heat. When the room temperature increases to the preset level, the thermostat’s signal ends, and the furnace stops producing heat. When the temperature again falls below the preset level, the cycle begins anew. In the body, secretion of a specific hormone is similary turned on or off(or up or down) by specific physiological changes.

Negative feedback is the primary mechanism through which the endocrine system maintains homeostasis. Using the example of plasma glucose concentrations and the hormone insulin, when the plasma glucose concentration is high, the pancrease releases insulin. Insulin increases cellular uptake of glucose, lowering plasma concentration of glucose. When plasma glucose concentration returns to normal, insulin release is inhibited until the plasma glucose level increases again.

Hormone receptors

The plasma concentration of a specific hormone is not always the best indicator of that hormone’s activity because the number of receptors on target cells can be altered to increase or decrease that cell’s sensitivity to the hormone. Most commonly, an increased amount of a specific hormone decreases the number of cell receptors available to it. When this happens, the cell becomes less sensitive to that hormone, because with fewer receptors, fewer hormone molecules can bind. This is reffered to as downregulation, or desensitization. In some people with obesity, for example, the number of insulin receptors on their cells appears to be reduced. Their bodies respond by increasing insulin secretion from the pancreas, so their plasma insulin concentrations increase. To obtain the same degree of plasma glucose control as normal, healthy people, these individuals must release much more insulin.

In a few instances, a cell may respond to the prolonged presence of large amounts of a hormone by increasing its number of available receptors. When this happens, the cell becomes more sensitive to that hormone because more can be bound at one time. This is reffered to as upregulation. In addition, one hormone occasionally can regulate the receptors for another hormone.

Prostaglandins

Prostaglandins, although technically not hormones, are often considered to be  a third class of hormones. These substances are derived from a fatty acid, arachidonic acid, and they are associated with the plasma membranes of almost all body cells. Prostaglandins typically act as local hormones, exerting their effects in the immediate area where they are produced. But some also survive long enough to circulate through the blood to affect distant tissues. Prostaglandin release can be triggered by many stimuli, such as other hormones or a local injury. Their functions are quite numerous because there are several different types of prostaglandins. They often mediate the effects of other hormones. They are also known to act directly on blood vessels, increasing vascular permeability(which promotes swelling) and vasodilatation. In this capacity, they are important mediators of the inflammatory response. They also sensitize the nerve endings of pain fibers; thus, they promote both inflammation and pain.

“Physiology of sport and exercise”, fourth edition; Jack H. Wilmore, David L. Costill, W. Larry Kenney