Anterior pituitary hormones

Hormones produced by the anterior lobe of the pituitary include growth hormone or somatotropin (GH, ST), thyrotropin (thyroid–stimulating hormone, or TSH), adrenocorticotropin (ACTH), endorphins (EN), enkephalins, dynorphins, follicle–stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (Dickson, 1970; Willmore and Costill, 1994). The first three play an important role in growth and development in the young animal and in metabolism in the adult animal. The endorphins, enkephalins, and dynorphins are opiate-like peptide hormones that modulate analgesia and immune function and interact with the neural pathways of the hypothalamic–pituitary axis to influence releasing and inhibiting hormones (McLaren et al., 1989; Mehl et al., 2000). FSH, LH, and prolactin are considered hormones essential for normal reproduction and lactation. Research in species other than horses has demonstrated that severe or prolonged exertion can alter their release and, thus, normal reproductive cycles (Dickson, 1970; Willmore and Costill, 1994). Furthermore, prolactin appears to play an important role in the response to severe stress, interacting with many of the metabolic hormones. Though FSH and LH are technically anterior pituitary hormones, their function will be discussed later in the chapter in relation to the gonadal hormones which they influence.

Growth hormone

GH affects all the cells in the body stimulating development and growth in younger animals. In mature animals, GH plays a vital role in muscle metabolism through its effects on protein synthesis and its role in fat and carbohydrate utilization (Dickson, 1970; Willmore and Costill, 1994). The importance of GH in maintenance of normal physiologic function and its possible role in slowing, or possibly even reversing, the effects of aging can be seen in some younger adult humans, where GH deficiency results in changes in appearance, decreased lean body mass, impaired immune function, and other “sequelae” of aging. Treatment of these individuals with recombinant human GH (hGH) results in increased lean body mass, decreased body fat, and increased muscle mass (Murray et al., 2001; Yarasheski, 1994). Chronic hGH administration also appears to increase strength and the ability to perform a battery of weight-lifting exercises in older male humans. These effects have led to increased doping with hGH in human athletes, partly because of improved repair and recovery as well as lack of valid tests for exogenous hGH until recently. Although there have been no reported effects of GH on aerobic capacity, the increase in muscle mass and strength have been shown to benefit the quality of life in humans by increasing the ability to do daily tasks such as maintaining balance while walking and climbing stairs. Those human experiments served as part of the justification for several recent studies of the efficacy of recombinant GH treatment in preventing or retarding functional decline in geriatric humans (Murray et al., 2001; Yarasheski, 1994) and in geriatric horses (Horohov et al., 1999; Malinowski et al., 1997; McKeever et al., 1997).

Researchers conducting equine studies have asked “quality of life” questions similar to those posed in experiments using older humans. Those studies demonstrated that GH therapy increases nitrogen retention and improves appearance in geriatric horses, but they did not demonstrate any effect of chronic GH administration on body weight or the dimensions of several key muscles measured using ultrasonography (Malinowski et al., 1997). Functionally, chronic GH administration did not alter aerobic capacity or several commonly used indices of exercise performance, at least not in unfit old mares (McKeever et al., 1997). Furthermore, data from unfit geriatric horses indicated that exogenous GH did not alter lactate tolerance or cause an increase in maximal power that one would associate with an increase in muscular strength, which is a logical observation, since there was no evidence of an increase in muscle mass (McKeever et al., 1997). It is possible that the lack of significant findings in the horse may be due to insufficient dosage of GH, as was common in many of the early studies on GH and anabolic steroids in humans. Interestingly, studies of geriatric male humans have shown that recombinant GH therapy results in increased muscle mass and, in some cases, increased strength as measured in standardized tests performed with weightlifting equipment. However, although GH therapy does appear to increase strength in humans, there are no data to show that GH therapy alters maximal aerobic capacity or enhances endurance performance (Murray et al., 2001; Yarasheski, 1994).

Some studies of younger horses have demonstrated that administration of GH prevents some of the bone demineralization that occurs in the first months of intense training. Other studies found that there was minimal or no therapeutic benefit of administering GH to prevent tendon or cartilage injuries or to promote wound healing (Gerard et al., 2001; Gerard et al., 2002). It has also been demonstrated that GH does not alter aerobic capacity or markers of performance in young (∼2 yr) Thoroughbreds (Gerard et al., 2001; Gerard et al., 2002). However, as with the studies of older horses, the experiments performed on younger animals had no way to evaluate the effects of GH administration on muscular strength. Data are clearly needed to determine if GH alters strength and power, with particular attention also paid to dose–response issues.

Thyrotropin

Release of TSH is stimulated by thyroid-releasing hormone (TRH), which is produced in the hypothalamus (Dickson, 1970; Willmore and Costill, 1994). Studies of humans and other species have demonstrated that acute exercise elicits mixed effects on TSH release. The release of TSH appears to be linked to exercise intensity, as mild and moderate exertions do not appear to have an effect on TSH release. However, there appears to be a threshold for stimulating TSH release, as plasma concentrations of this hormone increase with work intensity only when exercise intensity exceeds 50% of maximal oxygen uptake (O_2max) in humans. This breakpoint is common to several hormonal systems, including the observed increases in catecholamines, adrenocorticotropic hormone (ACTH), cortisol, plasma renin activity (PRA), etc. (Freund et al., 1991; Jimenez et al., 1993; Nagata et al., 1999). Interestingly, exercise duration beyond 40 minutes appears to also cause an increase in TSH. This observed increase during longer steady-state exertion is similar to the response of other metabolic hormones and may be related to substrate mobilization and attempts to prevent the onset of central fatigue mechanisms. Data on the effects of acute exercise and training on TSH in equine athletes are lacking.

Adrenocorticotropic hormone

The release of ACTH is stimulated by corticotropin–releasing hormone (CRH), which is secreted by the hypothalamus (Dickson, 1970; Willmore and Costill, 1994). A number of published papers have demonstrated that exercise causes an increase in ACTH in the horse; however, most of those only report postexercise, rather than during-exercise, values (Elsaesser et al., 2001; McCarthy et al., 1991). The major conclusion of most exercise studies has been that both high-intensity and long-duration endurance exercises cause an increase in ACTH and subsequent increase in cortisol. If one looks at the role of ACTH and glucocorticoids in substrate mobilization and utilization during exertion, it is apparent that the ACTH or cortisol response is an appropriate and adaptive response to physical exertion, which itself is a stressor (Elsaesser et al., 2001; McCarthy et al., 1991; Caloni et al., 1999). In fact, mobilization of the “stress response” provides for remarkable regulation of homeostasis. As the intensity of exercise increases (and, hence, the threat to homeostasis increases), the activation of the HPAA exponentially increases to handle the stress of exercise (Nagata et al., 1999).

The ACTH response appears to be highly correlated to the catecholamine and lactate responses to incremental exercise, all of which also increased in a curvilinear fashion (Nagata et al., 1999). When horses were exercised at 80% or 110% O_2max, the ACTH response was rapid, and concentrations increased in a linear fashion until the end of the exercise test (Nagata et al., 1999). Postexercise concentrations fell rapidly, returning to baseline within 60 to 120 minutes (Nagata et al., 1999). These responses are similar to those reported for humans and other species (Nagata et al., 1999; Willmore and Costill, 1994). With chronic exposure to a stressor, as would happen during overtraining, regulation of the HPAA is challenging, as exhaustion may result from the increased allostatic load.

Endorphins, enkephalins, and dynorphins

These peptides are released from the pituitary in response to stress, pain, or pleasure. Although some classify these substances as hormones, others classify them as neurotransmitters (McLaren et al., 1989; Mehl et al., 2000). Nevertheless, these substances are naturally occurring opiat-like analgesics primarily derived from the pre–prohormone proopiomelanocortin (POMC) that may allow a horse to tolerate higher-intensity exercise (Art et al., 1994; Caloni et al., 1999; Li and Chen, 1987; McCarthy et al., 1991; McLaren et al., 1989; Mehl et al., 2000). The endorphins, enkephalins, and dynorphins play a role in the response to physiologic and psychological stress and appear to modulate pain perception as well as immune responses (McLaren et al., 1989; Mehl et al., 2000). Given that an overload of duration, intensity, or resistance is needed for exercise training to elicit an adaptive response, the endorphins may play an important role in allowing a horse to better tolerate the progressive increases in exercise intensities or longer durations needed to improve fitness and performance. Mehl and coworkers (McLaren et al., 1989; Mehl et al., 2000) have demonstrated that a threshold exists for evoking an increase in plasma beta (β)-endorphin concentration. This threshold appears to correspond to approximately 60% O_2max. Interestingly, this is the same point where one sees a curvilinear increase in the catecholamines, plasma renin activity, plasma lactate concentration, and several other variables. This suggests a close interplay between these factors in the transition from low-intensity and primarily aerobic exercise to higher-intensity exercise with an increasing anaerobic component (Convertino et al., 1983; Freund et al., 1991; Jimenez et al., 1993; Nagata et al., 1999). Duration of exercise also appears to affect the magnitude of the endorphin response with greater plasma concentrations as horses approach fatigue (McLaren et al., 1989; Mehl et al., 2000). Training appears to alter the endorphin response to acute exertion with greater plasma concentrations observed in the postexertion peak occurring between 5 and 10 minutes after exertion (Malinowski et al., 2003).

Posterior pituitary hormones

Hormones released from the posterior lobe of the pituitary, which technically comprises neural tissue rather than glandular tissue, include arginine vasopressin (AVP) and oxytocin. These two protein hormones are actually produced in the hypothalamus by specialized bundles of nerves (Dickson, 1970; Willmore and Costill, 1994). Arginine vasopressin is synthesized in cells of supraoptic and paraventricular nuclei and stored in vesicles in the nerve endings located in the posterior pituitary. Oxytocin causes smooth muscle contraction in the epididymis of males and the uterus of females, and it also acts on mammary tissue causing milk let-down in lactating mares. However, oxytocin’s role in the response to exercise is unclear.

Arginine vasopressin

Arginine vasopressin (AVP), also known as antidiuretic hormone (ADH), is associated with acute as well as chronic defense of blood pressure, plasma volume, and fluid and electrolyte balance (Dickson, 1970; McKeever, 2002; McKeever and Hinchcliff, 1995; Wade, 1984; Zambraski, 1990). The physiologic actions of AVP include vasoconstriction and decreased free water clearance (McKeever and Hinchcliff, 1995; Wade, 1984; Willmore and Costill, 1994; Zambraski, 1990). AVP also plays a major role in the short-term and long-term control of cardiovascular function during and following exercise (Dickson, 1970; Willmore and Costill, 1994). Additionally, AVP is a critical stress hormone and serves as a secretagogue of ACTH. In fact, during acute exercise and in response to other noxious acute stressors (i.e., surgery, shock), AVP appears to be an even more potent stimulus for ACTH secretion than is CRH (Schmidtt et al., 1996).

The mechanism for the release of AVP primarily involves osmoreceptors in the supraoptic and paraventricular nuclei of the hypothalamus and cardiopulmonary baroreceptors in the atria of the heart (Dickson, 1970; McKeever and Hinchcliff, 1995; Wade, 1984; Zambraski, 1990). Data from rats and other species have shown that a very small 1% to 2% decrease in cell volume in the hypothalamus or change in extracellular osmolality of 2 to 4 milliosmole per kilogram (mOsm/kg) will stimulate secretion of AVP and intake of water (Wade, 1984). Exercise causes an increase in plasma AVP that is correlated with both duration and intensity (Convertino, 1991; Convertino et al., 1983; Wade, 1984). Comparative data show that AVP is secreted during exercise in concentrations well above the threshold level associated with its antidiuretic effects, suggesting that its extrarenal actions are more important during acute exercise (McKeever and Hinchcliff, 1995; McKeever et al., 1991a; McKeever et al., 1993; McKeever et al., 1991; McKeever et al., 1992b; Wade, 1984). Extrarenal actions include AVP’s action as a powerful vasoconstrictor, an ACTH stimulus, and an important component in the control of blood pressure during exercise and its action on splenic blood vessels to prevent resequestration of the splenic reserve in the horse (Davies and Withrington, 1973; McKeever and Hinchcliff, 1995). Interestingly, some studies suggest that drinking water, especially cold hypotonic water, during exercise may suppress AVP and thirst, leading to dehydration (Zambraski, 1990). However, sustained elevations in AVP stimulate thirst and drinking water after exercise, cause a decrease in free water clearance by the kidneys, and may influence the uptake of sodium and water from the colon (McKeever and Hinchcliff, 1995; Zambraski, 1990).

In exercising horses, plasma AVP concentration was recently reported to increase from approximately 4.0 picogram per milliliter (pg/mL) at rest to about 95 pg/mL at a speed of 10 meters per second (m/s). It was also reported that the relationship between AVP concentration and exercise intensity was curvilinear and did not plateau at speeds producing maximal heart rate (McKeever et al., 1992b). Another paper reported that AVP increases during steady-state submaximal exercise in horses without a change in free water clearance (McKeever et al., 1991a). However, the increase does not become significant until between 20 and 40 minutes of exertion (McKeever et al., 1991a). Two possible explanations have been given for the delay in AVP secretion in submaximally exercised horses (McKeever et al., 1991a). First, there appears to be a suppression of AVP secretion due to the volume overload sensed by the neural pathways associated with the atrial baroreceptors and the hypothalamus (McKeever and Hinchcliff, 1995; McKeever et al., 1991a). Second, AVP release is inhibited by the increase in atrial natriuretic peptide (ANP) concentrations at the beginning of exercise (McKeever and Hinchcliff, 1995; McKeever et al., 1991). Nevertheless, an increase in AVP concentration has been seen with prolonged exercise that appears to be related to sweat losses and decreases in body water that altered plasma osmolality and blood pressure (McKeever and Hinchcliff, 1995; McKeever et al., 1991; McKeever et al., 1992b). Studies of humans have demonstrated that training alters the slope of the AVP response to acute exercise, suggesting a change in the sensitivity to the exercise challenge (Freund et al., 1991; Convertino et al., 1983; Convertino, 1991). No studies on the effect of training on the AVP response to acute exertion in the horse have been published.

Triiodothyronine and thyroxine

The release of these hormones is stimulated by TSH which, as previously mentioned, is released during exercise. As with TSH, the release of T3 and T4 is associated both with the intensity and duration of exercise in humans and horses (Gonzalez et al., 1998; Willmore and Costill, 1994). Irvine (1967) demonstrated that training increases both the secretion rate of T3 and T4 by approximately 65%. This would indirectly support the suggestion that TSH, which increases with training in humans and other species, is also increased with training in the horse. Training also increases the turnover rate of the thyroid hormones, though not necessarily in a clinically relevant manner that would suggest hyperthyroid function (Willmore and Costill, 1994).

Calcitonin

In addition to its control of metabolic rate, the thyroid is vital to calcium homeostasis. For this function, the thyroid synthesizes and produces calcitonin (Dickson, 1970; Willmore and Costill, 1994). Calcitonin plays a role in calcium homeostasis either by inhibiting osteoclast activity in bone or through its action on the kidney tubules to cause an increase in calcium loss by actively inhibiting tubular reabsorption. New bone is formed by osteoblasts and reabsorbed by osteoclasts. In young growing horses, both osteoclasts and osteoblasts are active; however, the activity of osteoblasts outpaces the activity of osteoclasts, allowing for bone growth and development (Dickson, 1970). To this end, calcitonin appears to be more important in the young growing animal through its inhibitory action on the osteoclasts. Calcitonin is also important in the healing of fractures (Dickson, 1970). Chiba and coworkers (Chiba et al., 2000) documented substantially elevated plasma calcitonin concentrations in racehorses with various fractures. Studies have also demonstrated that there is a period of bone demineralization in young Thoroughbreds in the first few months of training. Growing and adult humans who exercise regularly have increased bone density (Willmore and Costill, 1994). Although a great deal of work has examined markers of bone turnover, more data are needed to determine if acute and chronic exertion affect plasma calcitonin concentrations (Chiba et al., 2000; Geor et al., 1995; Murray et al., 2001).

Hormones produced by the adrenal medulla (catecholamines)

The release of the catecholamines has its origin in the fight-or-flight response. This “stress” response involves the local release of NE from the sympathetic nerve endings (acting as a neurotransmitter) and a systemic release of E and NE from the adrenal medulla. Receptors for the catecholamines are specialized and are divided into two primary categories, referred to as alpha (α)- and beta (β)-adrenergic receptors. These two major categories are divided into subcategories, namely, α₁, α₂, β₁, β₂, and β₃ receptors (McKeever, 1993).

Sympathetic nervous activity increases with intensity and duration of exercise, but notable changes in plasma catecholamine concentrations are not always apparent below 50% of maximal aerobic capacity (McKeever, 1993). Plasma catecholamine levels increase in a curvilinear fashion with increasing exercise intensity and are highly correlated with plasma lactate concentrations (Gonzalez et al., 1998; Jimenez et al., 1993; Nagata et al., 1999). The measurable increase appears to coincide with the intensity at which one would expect complete parasympathetic withdrawal (Freund et al., 1991; Jimenez et al., 1993; Nagata et al., 1999). These increases in the catecholamines, particularly E, enhance the increase in heart rate (a chronotropic effect), force of cardiac contraction (an inotropic effect), and cardiac output (McKeever, 1993; McKeever and Hinchcliff, 1995). The catecholamines also play a role inducing splenic contraction and the delivery of 6 to 12 liters (L) of blood into the central circulation at the onset of exercise in horses (McKeever, 1993; Persson, 1967). Even with this mobilization of reserve blood volume, the demands of exercise may exceed central cardiovascular capacity in the horse. Thus, during high-intensity exercise or long-duration exercise, the catecholamines contribute to the vasoconstriction that decreases blood flow to nonobligate tissues (McKeever, 1993; McKeever and Hinchcliff, 1995; Rowell, 1993).

The catecholamines are also linked with the respiratory response to exercise (Jimenez et al., 1993; McKeever, 1993; McKeever and Hinchcliff, 1995; Plummer et al., 1991; Sexton and Erickson, 1986; Snow and Rose, 1981). At the onset of exercise the β₂-adrenergic receptor action relaxes tracheal and bronchial smooth muscle, increasing airway diameter, decreasing airway resistance, and, thus, facilitating movement of greater amounts of air into and out of the lungs. Although the sympathetic system is not directly responsible for the control of ventilation during exercise, the increase in ventilatory drive associated with activation of the motor cortex can be enhanced during exercise by catecholamine secretion and augmentation of the sensitivity of chemoreceptors in the carotid bodies. During high-intensity exercise, ventilation may be further affected by catecholamine release as part of the stress response (McKeever, 1993).

The catecholamines also have major effects on metabolic pathways associated with substrate utilization during exercise (McKeever, 1993; Willmore and Costill, 1994). Increases in sympathetic activity result in an increase in hormone-sensitive lipase and, subsequently, an increase in circulating free fatty acids. Exercise-induced and anticipatory secretion of catecholamines also cause an increase in glycogen breakdown resulting in increased glucose availability. It has been suggested that one way that warmup exercises benefit the athlete is through activation of these metabolic pathways, which allows for elevated blood concentrations of glucose and free fatty acids prior to race-induced increases in utilization, thus facilitating delivery of substrate to tissues without a significant lag time (McKeever, 1993; Willmore and Costill, 1994).

The above-mentioned responses have been well documented during acute exercise. Recent data also suggest that exercise training alters adrenergic receptor numbers and sensitivity in selected tissues. For example, β-adrenergic receptor numbers are unchanged in cardiac muscle with training, whereas α-adrenergic and muscarinic receptor numbers are reduced. Both β-adrenergic receptor numbers and sensitivity are increased in skeletal muscle and in vascular and bronchial smooth muscle (McKeever, 1993; Willmore and Costill, 1994). Changes in receptor number and sensitivity with training may be important with respect to adjustment of drug doses for the animal that has been trained extensively versus an animal that is at the beginning of a training program or one that is being reconditioned following removal from training (McKeever, 1993; Willmore and Costill, 1994).

Primary hormones produced by the adrenal cortex

Some sources suggest that more than 30 structurally distinct steroid hormones are secreted by the adrenal cortex. Secretion of the mineralocorticoid aldosterone and the glucocorticoid cortisol is, however, the most important to the physiologic response to exercise (Dickson, 1970; Willmore and Costill, 1994).

Aldosterone

Aldosterone plays an important role in electrolyte homeostasis, particularly sodium and potassium balance (Dickson, 1970; McKeever, 1998; McKeever and Hinchcliff, 1995; Willmore and Costill, 1994). It is well recognized that aldosterone acts on the kidneys to enhance sodium (and chloride) reabsorption and potassium excretion. Aldosterone also acts on the intestines to facilitate the uptake of electrolytes and water. Aldosterone release can be stimulated by decreases in plasma [Na⁺] or by increases in plasma [H⁺], plasma [K⁺], plasma ACTH, by increased renin (McKeever and Hinchcliff, 1995; McKeever, 1998), or by both. However, the most potent of these stimuli is an increase in plasma [K⁺] (McKeever, 1998; McKeever and Hinchcliff, 1995). Studies of horses have attempted to identify factors that may stimulate the release of aldosterone during exercise (Cooley et al., 1994; McKeever et al., 1987; McKeever, 1998; McKeever et al., 1991a; McKeever et al., 1992b; McKeever et al., 1997; ). In one study, plasma [Na⁺] was not significantly affected by exercise and thus, a decrease in plasma [Na⁺] did not appear to have been the primary stimulus for aldosterone release (McKeever et al., 1991a). The primarily supported mechanism for the release of aldosterone appears to be a proportional increase in the plasma renin–angiotensin–aldosterone cascade, where an increase in renin results in the generation of angiotensin I and angiotensin II, with angiotensin II stimulating the production and release of aldosterone (Costill et al., 1976; Kosunen and Pakarinen, 1976; McKeever et al., 2000; Zambraski, 1990).

The relationship between plasma aldosterone concentration and exercise intensity has been reported in horses running on a treadmill. Aldosterone increased from concentrations around 20 to 50 pg/mL at rest to almost 200 pg/mL at a speed of 10 m/s (Kokkonen et al., 2002; McKeever et al., 1992b). A linear relationship was found between exercise intensity and aldosterone concentration. However, unlike renin, aldosterone concentration did not reach a plateau at maximal heart rate (HR_MAX). Another study found that during submaximal exercise, increases in plasma aldosterone concentration paralleled changes in renin but that the magnitude of the increase in renin (66%) was less than the relative increase (709%) in aldosterone concentration (McKeever et al., 1991a). The authors concluded that factors other than renin also affected the release of aldosterone in the horse (McKeever et al., 1991a). Of all the parameters reported, a significant increase in plasma [K⁺] may have served as the strongest stimulus for the release of aldosterone (McKeever and Hinchcliff, 1995). An increase in plasma [K⁺] as small as 0.3 milliequivalent per liter (mEq/L) can be sufficient to stimulate the secretion of aldosterone, independent of the renin–angiotensin cascade, through the conversion of cholesterol to pregnenolone or at a later step in the biosynthetic pathway (McKeever and Hinchcliff, 1995). This is consistent with the acute homeostatic requirements of the horse, since a major perturbation in electrolyte homeostasis observed during endurance exertion was an increase in plasma [K⁺] and not a drop in plasma [Na⁺] (McKeever et al., 1992b). As with humans, aldosterone has a minimal role in the acute response to exercise in horses. However, aldosterone concentration remains elevated for hours after exercise and may affect the long–term reabsorption of sodium and water (Convertino, 1991; Hyyppa et al., 1996; McKeever, et al., 2002b) by the kidneys and by the intestinal tract (Bridges and Rummel, 1984; Kokkonen et al., 2002)

Cortisol

The major glucocorticoid secreted by the adrenal glands is cortisol. However, some cortisone, corticosterone, and deoxycorticosterone are also produced (Dickson, 1970; Willmore and Costill, 1994). Cortisol, cortisone, and corticosterone can be found in a ratio of 16:8:0.5 in the plasma of horses; therefore, most exercise studies have focused on cortisol (Dickson, 1970). Cortisol undergoes diurnal variation, with peak levels found in the early morning between 06:00 and 10:00 and lowest levels found in the late evening and overnight periods (Dickson, 1970; Willmore and Costill, 1994). Although glucocorticoids are typically, and correctly, referred to as “stress” hormones, they are also released under a multitude of normal situations not necessarily characterized as stressful. Thus, it is the appropriateness of their release and the magnitude of their release that would indicate whether a given physiologic or psychological disturbance (or stressor) can be classified as a mere perturbation or a true threat to homeostasis.

Release of cortisol allows an individual to tolerate and adapt to challenges to homeostasis that occur in everyday life. To this end, the functional effects of cortisol fall into two major categories: (1) substrate mobilization and (2) immune modulation (Dickson, 1970; Willmore and Costill, 1994). During acute exercise, itself a distinct challenge to homeostasis and a unique stressor, cortisol stimulates substrate mobilization by enhancing gluconeogenesis, mobilizing free fatty acids through lipolysis, and increasing the availability of amino acids through protein degradation (Willmore and Costill, 1994). At the same time, cortisol release decreases glucose utilization by nonessential tissues to spare it for use by the central nervous system (Willmore and Costill, 1994). One could speculate that such an action could delay the onset of central fatigue that occurs during endurance exertion when blood glucose concentrations drop (Farris et al., 1998; McKeever, et al., 2002b). The increase in protein catabolism results in amino acid availability as a source of energy when glucose levels begin to drop. They are available after exercise to repair tissues and for the synthesis of enzymes involved in many cellular pathways. Cortisol’s modulation of immune function results from its actions as an antiinflammatory agent and suppressor of immune reactions (Dickson, 1970; Willmore and Costill, 1994).

Overall, these actions may be of significant benefit in the response to training. Overload through increased exercise intensity, resistance, or duration is necessary for training to stimulate an adaptive response to exercise. The minor disruption of function and structure in the cells of muscles results in protein accretion, substrate uptake and deposition, and other beneficial remodeling that increases the functional capacity of the cells. Cortisol’s suppression of immune function and antiinflammatory effects may actually provide a permissive environment for tolerating the slight amount of “muscle damage” needed for training-induced remodeling. In this context, it is likely that cortisol serves as an important signal for cellular and muscular repair following intense training. Though cortisol is a catabolic hormone, it would be incorrect to interpret its acute secretion during exercise as an undesirable event if optimal adaptations to training are desired. Instead, cortisol clearance and recovery from the stressor may be the more important physiologic occurrences.

Many studies have demonstrated that cortisol is increased in the horse during a wide variety of exercise activities, from racing, to polo, to endurance rides (Caloni et al., 1999; Crandell et al., 1999; Horohov et al., 1999; Hyyppa, 2001; Snow and MacKenzie, 1977; Snow and Rose, 1981). The release of cortisol in the horse appears to be affected both by intensity and duration of exercise (Snow and MacKenzie, 1977; Snow and Rose, 1981). However, excessive increases in cortisol concentrations following exertion can be a marker of too much exercise. Prolonged cortisol recovery times as well as either inappropriately high or low plasma concentrations of cortisol may be a marker of overtraining in the horse. As mentioned above, postexertion effects of cortisol may elicit a permissive effect that is beneficial for training adaptation by preventing the immune system from eliciting an inflammatory and immune reaction to acute exercise (Horohov et al., 1999; Toutain, et al., 1995). Several studies on horses have followed cortisol levels for extended periods following exercise. Those experiments demonstrated that exercise caused a sixfold increase in adrenal cortisol secretion and a two- to three-fold increase in plasma cortisol concentration. Urinary cortisol concentrations also increased threefold with a return to baseline levels by 10 hours after exertion (Toutain, et al., 1995). The authors also noted a substantial increase in liver clearance of cortisol.

Prior studies have suggested that peak postexercise cortisol concentrations are reached earlier in trained horses and that trained horses have a faster cortisol recovery time (Snow and MacKenzie, 1977; Snow and Rose, 1981). On average, peak cortisol levels were observed at about 30 minutes after exertion. Much of this enhanced recovery would be dependent on optimal training volume and rest to produce training adaptations. Still, improved training status may improve the potential to rapidly switch from a catabolic state to an anabolic state.

Insulin

Insulin functions as part of the feedback system controlling blood glucose concentration (Dickson, 1970; Willmore and Costill, 1994). Insulin is primarily a glucose “storage” hormone because it facilitates glucose uptake by the cells, promotes glycogenesis, and inhibits gluconeogenesis (Dickson, 1970; Giraudet et al., 1994; Ralston, 1992; Willmore and Costill, 1994). As such, it is arguably the most potent anabolic hormone. At rest, insulin is the “key” that opens the cellular door to allow uptake of glucose. However, during exercise, the working muscles take up glucose without insulin. Thus, insulin is very important during the recovery from exercise when glycogen repletion is most active (Dickson, 1970; Davie et al., 1994; Davie et al., 1999; De La Corte et al., 1999; Willmore and Costill, 1994).

The insulin response to acute exercise has been well documented with the horse which, like humans and other species, suppresses insulin during exercise (Duren et al., 1999; Geor et al., 2000; Snow and Rose, 1981). This suppression appears to have a threshold of 50% of O_2max, which coincides with the increase in catecholamines seen during exercise (McKeever, 2002). Mechanistic studies have demonstrated the link between exercise-induced increases in sympathetic drive, particularly due to epinephrine’s inhibitory effects on insulin, and changes in insulin and glucagon secretion in the horse (Geor et al., 2000). Functionally, this allows the animal to increase gluconeogenesis to maintain blood glucose concentrations during exercise (Geor et al., 2000; Willmore and Costill, 1994). Suppression of insulin and maintenance of blood glucose concentration prevents the onset of central mechanisms of fatigue (Farris et al., 1998; McLaren et al., 1989). Much of the recent work on the insulin response to exertion has centered on the composition and timing of pre-exercise feeding (Crandell et al., 1999; Frape, 1988; Hyyppa et al., 1999; Pagan and Harris, 1999; Poso and Hyyppa, 1999). High-carbohydrate feeds are beneficial for optimal muscle glycogen synthesis to fuel exercise. However, the resultant increase in blood glucose seen after a horse eats a high-carbohydrate ration usually evokes an increase in insulin secretion. The goal of recent research has been to prevent this feed-induced spike in insulin that would tend to decrease blood glucose right before or during exercise (Williams et al., 2001a). This phenomenon has often been referred to as “rebound hypoglycemia” (Jentjens and Jeukendrup, 2002). Recent research in humans has suggested that rebound hypoglycemia may be influenced by the timing of carbohydrate intake and the intensity of the exercise but that any hypoglycemic effects may have little, if any, impact on performance (Moseley et al., 2003).