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11 The Endocrine Response to Exercise

Illustration of a human figure engaged in running overlaid with labeled anatomical representations of key endocrine glands. These include the hypothalamus, pituitary gland, thyroid, adrenal glands, pancreas, and gonads.
Exercise and the Endocrine System.

Learning Objectives

  • Identify the three classes of hormones based on their chemical makeup.
  • Discuss how the chemical composition of hormones affects their transport in the blood and interaction with tissues.
  • Describe how hormones like insulin facilitate glucose uptake in cells.
  • Explain the G protein-coupled receptor mechanism and its significance in cellular responses. 
  • Identify the endocrine glands most affected by exercise and the hormones they secrete.
  • Explain how changes in plasma volume and osmolality during exercise influence hormone secretion.
  • Describe the primary hormones secreted by the adrenal medulla and cortex and their roles during exercise.
  • Explain the renin-angiotensin-aldosterone system and its importance in maintaining plasma volume during exercise.
  • Explain the functions of testosterone and estrogens in the body and their influence on exercise performance.
  • Describe how anabolic hormones like testosterone, GH, insulin, and IGF-1 contribute to muscle hypertrophy and remodeling during resistance training.
  • Compare the acute and chronic hormonal responses to resistance training and their significance.

Introduction

        As discussed in previous chapters, exercise acts as a stressor on the body, disrupting homeostasis and leading to various acute and chronic changes. Two major homeostatic systems involved in regulating bodily functions are the nervous and endocrine systems. These systems work together to sense information, organize appropriate responses, and send messages to tissues to maintain or regain homeostasis. The term neuroendocrinology is often used to describe the systematic study of these control systems, as endocrine organs receive neural input. The nervous system relays messages via action potentials and neurotransmitters, whereas the endocrine system communicates by releasing hormones (chemical messengers) into the blood to circulate and exert effects. Hormones attach to highly specific receptors to trigger cellular responses. In the context of exercise physiology, hormones are crucial for mobilizing fuel for exercise, stimulating protein synthesis, and initiating muscle hypertrophy. The specific responses of the endocrine system to acute and chronic exercises will be discussed in this chapter.

Categories of Hormones

        Hormones can be categorized into three classes based on their chemical makeup: amino acid derivatives, peptides/proteins, and steroid hormones. The chemical composition of hormones determines their transport in the blood and interaction with tissues. Steroid hormones, being lipid-like, require that they are transported bound to plasma proteins and can diffuse through cell membranes to affect the nucleus. The effect of a hormone on a tissue is directly related to its plasma concentration and the number of active receptors. For example, steroid hormones like thyroxine use transport proteins, and their concentration is influenced by the availability of these proteins. Factors such as secretion rates, metabolism or excretion rates, and changes in plasma volume can affect free plasma hormone concentration and the magnitude of their effects. During exercise, plasma volume decreases due to sweating, increasing the hormone concentrations in the plasma and leads to enhanced metabolic and cellular changes.
        Endocrine hormones are carried by the blood to various tissues but only affect those with specific protein receptors. The number of receptors on each cell can range from 500 to 100,000 and can change based on chronic hormone levels. Receptor numbers may decrease (down-regulation) with chronically elevated hormone levels or increase (up-regulation) with low hormone concentrations. High hormone levels can saturate receptors, preventing additional hormonal effects. When a hormone binds to its receptor, it modifies cellular activity through three main mechanisms: altering DNA activity, altering membrane transport activity, and activating second messenger proteins. These mechanisms will be discussed in further detail in the next sections.

Altering DNA activity

        Hormones that alter DNA activity initiate protein synthesis in the nucleus. Steroid hormones, due to their lipid-like structures, can easily diffuse through cell membranes. These hormones, originating from the adrenal cortex and gonads, bind to protein receptors in the cytoplasm, forming a steroid-receptor complex. This complex then enters the nucleus and binds to a hormone response element on the DNA, leading to gene transcription to mRNA, subsequent protein synthesis, finally resulting in metabolic effects. Although thyroid hormones are not steroids, they also act by altering DNA. This process is slow but results in long-lasting effects compared to hormones that work through second messengers. Figure 11.1 illustrates this process.
Diagram illustrating the cellular mechanism of steroid hormone action. Step 1: A steroid hormone, due to its lipophilic nature, diffuses through the cell membrane into the cytoplasm. Step 2: It binds to a specific intracellular receptor, forming a hormone-receptor complex. Step 3: This complex translocates into the nucleus, where it binds to a hormone response element on the DNA, initiating transcription. Step 4: Messenger RNA (mRNA) is synthesized, exits the nucleus, and is translated into a functional protein by ribosomes with the help of transfer RNA (tRNA). The figure emphasizes the direct genomic action of steroid hormones in regulating gene expression.
Figure 11.1 The mechanism by which steroid hormones alter DNA activity. Steroid hormones, being lipophilic, diffuse through the cell membrane (1) and bind to a protein receptor in the cytoplasm. This binding creates a hormone-receptor complex (2) that translocates to the nucleus. Within the nucleus, the (3) hormone-receptor complex binds to the hormone response element on the DNA, regulating protein transcription. Messenger RNA (mRNA) is then transcribed, exits the nucleus, and is (4) translated into a functional protein by transfer RNA (tRNA) and ribosomes.

Altering membrane transport activity

        Polypeptide hormones exert their primary effects by binding to receptors on the cell surface, thereby altering membrane transport activity. Composed of chains of amino acids, these hormones are not fat-soluble and cannot cross the cell membrane. When polypeptide hormones bind to their receptors, they can activate carrier molecules or increase the movement of ions or substrates from outside to inside the cell. A prime example of this mechanism is the action of insulin. Insulin facilitates the influx of glucose into cells by binding to the extracellular domain of the insulin receptor. Due to its size, glucose cannot naturally diffuse into cells, yet it is an essential nutrient for all tissues. In cases of inadequate insulin response, such as in uncontrolled diabetes, glucose accumulates in the blood, leading to complications in various organ systems and tissues. The specific mechanism by which insulin enables glucose entry into cells involves several steps: 
  1. Insulin binds to the alpha subunit of a tyrosine kinase receptor located outside the cell.
  2. Binding causes the beta subunits inside the cell to phosphorylate themselves.
  3. The activation of these subunits leads to the movement of glucose transporters, known as GLUT4 transporters, to the cell membrane.
  4. GLUT4 transporters then facilitate the entry of glucose into the cell.
        Additionally, insulin activates glycogen synthase, an enzyme that converts glucose molecules into glycogen within the cell. Figure 11.2 illustrates the translocation of GLUT4 glucose transporters to the cellular membrane following insulin signaling.
Diagram showing the cellular mechanism of glucose uptake following insulin signaling. Insulin binds to its receptor on the cell membrane, initiating an intracellular signaling cascade. This cascade results in the translocation of GLUT4 glucose transporters from intracellular vesicles to the cell surface. Once embedded in the membrane, GLUT4 facilitates the entry of glucose into the cell. The glucose is then either metabolized for energy or stored as glycogen. The figure emphasizes the role of insulin in regulating glucose homeostasis via GLUT4-mediated transport.
Figure 11.2. Transport of glucose following GLUT4 translocation to the cell membrane after insulin signaling. Insulin binds to its receptor on the cell surface, triggering a signaling cascade that results in the translocation of GLUT4 transporters to the cell membrane. Once at the membrane, GLUT4 transporters facilitate the entry of glucose into the cell, allowing it to be used for energy or stored as glycogen.

Second Messenger Receptor Mechanism

        Due to their solubility, size, or specific function, some hormones cannot cross the cell membrane. Instead, they bind to receptors coupled to G proteins on the cell surface. The G protein, acting as a secondary messenger, can then activate enzymes within the cell, open ion channels, and ultimately lead to a cellular response. This mechanism serves as the link between the hormone-receptor interaction on the cell membrane and the subsequent intracellular events.
        When a hormone binds to its receptor, the G protein is activated, which can trigger a cascade of activities. One significant pathway involves the activation of adenylate cyclase, an enzyme that converts ATP to cyclic AMP (cAMP). Cyclic AMP then activates protein kinase A, which in turn activates response proteins that alter cellular activity. This pathway can lead to the activation of phosphorylase, which breaks down glycogen into glucose, and hormone-sensitive lipase, which breaks down triglycerides into free fatty acids. Figure 11.3 illustrates the cyclic AMP secondary messenger mechanism. Cyclic AMP is eventually inactivated by the enzyme phosphodiesterase, which converts it to 5’ AMP. Caffeine is known to inhibit phosphodiesterase activity, thereby prolonging the effects of cAMP. This prolonged activity can enhance the breakdown of triglycerides in adipose tissues, demonstrating caffeine’s impact on metabolic processes.
Diagram illustrating the cyclic AMP (cAMP) secondary messenger pathway. A hormone binds to a G protein-coupled receptor on the cell membrane, activating an associated G protein. The G protein then stimulates adenylate cyclase, which converts ATP into cyclic AMP (cAMP). cAMP acts as a secondary messenger, activating protein kinase A. This kinase then activates a response protein, initiating cellular processes such as the breakdown of fuels to support exercise. The figure emphasizes the role of cAMP in amplifying hormonal signals within the cell.
Figure 11.3 The cyclic AMP (cAMP) secondary messenger mechanism. Hormones bind to the G protein-coupled receptor on the plasma membrane, activating a G protein. The G protein then activates adenylate cyclase, which converts ATP to cyclic AMP. Cyclic AMP activates protein kinase A, which in turn activates a response protein, leading to the breakdown of fuels for exercise.

Secretion of Hormones and the General Exercise Response

        This section highlights the key endocrine glands involved in the body’s response to exercise and training. Understanding these glands, their regulatory mechanisms, and the hormones they release is crucial for discussing the role of the endocrine system in fuel mobilization during exercise. While this overview is not exhaustive, it focuses on the glands and hormones most affected by exercise.
        The rate of hormone secretion is influenced by both inhibitory and stimulatory signals from the nervous system. For instance, changes in calcium ion (Ca2+) concentration or substrate levels, such as blood glucose, can stimulate hormone release. Additionally, the rate of hormone secretion is affected by the liver’s ability to inactivate hormones and the kidneys’ role in hormone metabolism and excretion. During exercise, blood flow to these organs decreases, which slows the metabolism of hormones, thereby affecting their concentration and activity in the body. Figure 11.4 illustrates the major endocrine organs affected by exercise and their anatomical location.
Anterior anatomical diagram of the human body highlighting the major endocrine organs. Labeled structures include the hypothalamus and pituitary gland in the brain, the thyroid and parathyroid glands in the neck, the adrenal glands atop the kidneys, the pancreas in the abdominal cavity, and the gonads (ovaries in females, testes in males) in the pelvic region. The figure emphasizes the spatial distribution of endocrine organs responsible for hormone production and regulation throughout the body.
Figure 11.4 Anatomical Locations of Major Endocrine Organs in the Human Body.

Hypothalamus and the Pituitary Gland

        The hypothalamus, located in the brain, plays a crucial role in maintaining general homeostasis by controlling various body functions and is shown in Figure 11.5. During exercise, the regulation of hormone release, fluid intake, and temperature control becomes increasingly important, as exercise acts as a stressor to these systems. The hypothalamus exerts its control over the pituitary gland, which is situated at the base of the brain and is attached to the hypothalamus. The pituitary gland is divided into two lobes: the anterior pituitary (adenohypophysis) and the posterior pituitary (neurohypophysis). These lobes are responsible for the secretion of hormones that play vital roles in the body’s response to exercise and overall homeostasis.
Illustration of the human brain highlighting the hypothalamus and pituitary gland. The hypothalamus is shown near the base of the brain, responsible for regulating essential functions such as body temperature, hunger, and thirst. Just below it, the pituitary gland—often called the “master gland”—is depicted, releasing hormones that influence growth, metabolism, and reproductive processes. The figure emphasizes the anatomical proximity and functional relationship between these two key endocrine structures.
Figure 11.5 The hypothalamus and pituitary glands in the brain. The hypothalamus regulates vital bodily functions such as temperature, hunger, and thirst, while the pituitary gland, often termed the “master gland,” controls various endocrine functions by releasing hormones that influence growth, metabolism, and reproductive processes.

Anterior pituitary and its hormones

         The anterior pituitary gland is primarily regulated by chemical releasing hormones originating from neurons in the hypothalamus. Most hormones secreted by the anterior pituitary control the release of other hormones throughout the body. Key anterior pituitary hormones include adrenocorticotrophic hormone (ACTH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and growth hormone (GH). Other hormones such as melanocyte-stimulating hormone (MSH), follicle-stimulating hormone (FSH), and prolactin are less relevant to the direct changes associated with exercise.
  • Adrenocorticotrophic Hormone (ACTH): Stimulates the production and secretion of cortisol in the adrenal cortex in response to stress.
  • Luteinizing Hormone (LH): Stimulates the production of testosterone and estrogen.
  • Thyroid-Stimulating Hormone (TSH): Regulates the rate and secretion of thyroid hormones.
  • Growth hormone (GH) stimulates the release of insulin-like growth factors (IGFs) from the liver and other tissues, promoting protein synthesis and tissue growth.
The anterior pituitary plays a crucial role during exercise by secreting key hormones necessary for the body’s response.

Growth Hormone (GH) and its regulation

        Growth hormone (GH) stimulates the release of insulin-like growth factors (IGFs) from the liver and other tissues, promoting protein synthesis and tissue growth. The hypothalamus controls GH release in response to stimuli such as exercise, sleep, stress, and low plasma glucose levels. When stimulated, the hypothalamus releases growth hormone-releasing hormone (GHRH), which then prompts the anterior pituitary to release GH. GH is particularly important during exercise as it aids in energy mobilization. Specifically, GH increases liver gluconeogenesis and inhibits glucose entry into adipose tissue, favoring fat mobilization. Conversely, somatostatin, another hormone secreted by the hypothalamus, inhibits GH release from the anterior pituitary. The levels of GH and IGFs in the blood exert a negative feedback effect on the hypothalamus, regulating the continued secretion of GH. This negative feedback loop ensures that GH levels are maintained within an optimal range, as illustrated in Figure 11.6.
Diagram of the negative feedback loop regulating growth hormone (GH) release, particularly in response to exercise. The hypothalamus secretes growth hormone-releasing hormone (GHRH), which stimulates the anterior pituitary to release GH. GH acts on target tissues such as the liver and adipose tissue, promoting metabolic effects and stimulating the production of insulin-like growth factors (IGFs). IGFs exert downstream physiological effects and contribute to the feedback loop. Somatostatin, also released by the hypothalamus, inhibits GH secretion. The figure emphasizes the hormonal regulation and feedback mechanisms involved in GH control during physical activity.
Figure 11.6 The Growth Hormone (GH) Negative Feedback Loop Stimulated by Exercise. Growth hormone release is controlled by the hypothalamus through the secretion of growth hormone-releasing hormone (GHRH). Somatostatin inhibits GH release from the anterior pituitary. When released, GH targets various tissues in the body, including the liver, adipose tissue, and others. Additionally, the release of GH stimulates the production of insulin-like growth factors (IGFs), which have downstream effects.

Posterior pituitary gland

        The posterior pituitary gland stores hormones produced by specialized neurons in the hypothalamus. It primarily stores and releases oxytocin and antidiuretic hormone (ADH). Oxytocin is a potent stimulator of smooth muscle, playing a crucial role in childbirth and milk release from the breast. ADH, on the other hand, reduces water loss by promoting water reabsorption in the kidney tubules. High plasma osmolality (low water concentration) due to sweating without fluid replacement and low plasma volume can stimulate ADH secretion by the hypothalamus. During exercise, as plasma volume decreases and osmolality increases due to sweating, ADH secretion is elevated. Studies indicate that at exercise intensities above 60% VO2max stimulate ADH secretion to conserve water and maintain plasma volume [1]. These responses are vital for maintaining blood pressure and cardiovascular function during exercise.

Thyroid and Parathyroid Glands

        The thyroid gland is essential for establishing metabolic rate through the secretion of thyroid hormones. Stimulated by TSH from the anterior pituitary, the thyroid synthesizes two iodine-containing hormones: triiodothyronine (T3) and thyroxine (T4). T3 contains three iodine atoms, while T4 contains four. Although T4 is released in larger quantities, T3 is more potent. Thyroid hormone secretion is regulated by a negative feedback mechanism. During exercise, the concentration of free thyroid hormones increases due to changes in the binding characteristics of transport proteins, leading to faster uptake by tissues. To counteract the higher rate of hormone removal, thyroid-stimulating hormone (TSH) secretion increases. Exercise-induced secretion of prolactin and cortisol can also influence TSH release, affecting metabolism and enhancing the effects of other hormones. Figure 11.7 illustrates the location of the thyroid and parathyroid glands.
Anterior view diagram of the human neck showing the anatomical positions of the thyroid and parathyroid glands. The thyroid gland is located at the front of the neck, just below the larynx, and is responsible for producing hormones that regulate metabolism, energy levels, and growth. Behind the thyroid are the smaller parathyroid glands, typically four in number, which secrete parathyroid hormone (PTH) to maintain calcium balance in the blood and bones. The figure emphasizes the close anatomical relationship and distinct hormonal functions of these endocrine glands.
Figure 11.7 Diagram Showing the Position of the Thyroid and Parathyroid Glands. The thyroid gland produces hormones that regulate metabolism, energy levels, and growth. The parathyroid glands, located behind the thyroid, produce parathyroid hormone (PTH), which is crucial for maintaining stable calcium levels in the blood and bones.

Calcium regulation and parathyroid hormone

        Calcium ions (Ca2+) play a crucial role in muscle force production, making their regulation vital during exercise. The primary hormone involved in calcium regulation is parathyroid hormone (PTH), secreted by the parathyroid glands in response to low plasma calcium levels. PTH stimulates the release of calcium from bones into the plasma and enhances renal calcium reabsorption. Additionally, PTH promotes the conversion of vitamin D3 into its active form in the kidneys, which increases calcium absorption from the gastrointestinal tract. During both intense and prolonged exercise, PTH levels rise, which is also associated with increased plasma hydrogen ion (H+) and catecholamine concentrations [2]. The thyroid gland also secretes calcitonin, a hormone with a lesser role in calcium regulation. Calcitonin helps control plasma calcium levels by inhibiting calcium release from bones and promoting calcium excretion by the kidneys. Unlike PTH, calcitonin secretion is not significantly influenced by exercise.

Pancreas

        The pancreas functions as both an exocrine and endocrine gland. It secretes digestive enzymes and bicarbonate into the small intestine and contains endocrine tissues known as the islets of Langerhans. These islets release insulin, glucagon, and somatostatin. Somatostatin, secreted by delta cells, modulates gastrointestinal activity to regulate the entry rate of nutrients into the bloodstream. Insulin and glucagon, which are significantly affected by exercise, will be discussed in more detail in this section.
Diagram showing the anatomical location and dual functions of the pancreas. Positioned in the abdomen behind the stomach, the pancreas is illustrated with connections to the digestive tract. The figure highlights its exocrine role in producing digestive enzymes that break down carbohydrates, fats, and proteins, and its endocrine role in regulating blood glucose levels through the secretion of insulin and glucagon. The image emphasizes the pancreas’s central role in both digestion and metabolic homeostasis.
Figure 11.8 The Location and Functions of the Pancreas. The pancreas is in the abdomen behind the stomach. It plays a crucial role in digestion by producing enzymes that help break down carbohydrates, fats, and proteins. Additionally, it regulates blood sugar levels by secreting hormones such as insulin and glucagon.

Insulin and its role in glucose regulation

        Insulin, released from the beta cells of the islets of Langerhans in the pancreas, is the most crucial hormone during the absorptive state of digestion. It stimulates tissues to uptake nutrient molecules such as glucose and amino acids, promoting their storage as glycogen, proteins, and fat. Insulin is essential for facilitating the diffusion of glucose across cell membranes, as glucose cannot naturally diffuse across these membranes due to its size. When the insulin response is impaired, plasma glucose accumulates, leading to systemic issues in various organs and tissues. High plasma glucose levels overwhelm the kidneys’ reabsorption mechanisms, resulting in glucose loss in the urine along with large volumes of water, a condition known as diabetes mellitus.
        Insulin release is regulated by several factors, including plasma glucose concentration, plasma amino acid concentration, sympathetic and parasympathetic nerve stimulation, and various hormones. Blood glucose concentration is a major excitatory input to the beta cells of the pancreas and is part of the negative feedback loop that regulates insulin secretion. Following carbohydrate consumption and absorption, a temporary state of hyperglycemia occurs, with blood glucose levels rising above 100 mg/100 ml, compared to the normal fasting levels of 80-90 mg/100 ml. In response, the beta cells in the pancreas rapidly release insulin into the bloodstream. Insulin then binds to cell receptors, allowing glucose to be transported into the cells, thereby lowering blood glucose concentrations. This process restores blood glucose levels to normal, maintaining homeostasis through a negative feedback mechanism. In summary, insulin release in response to high blood glucose levels works by opposing the stimulus, reducing the amount of circulating blood glucose. After consuming carbohydrates, plasma glucose levels rise, prompting the beta cells to secrete insulin. Figure 11.9 illustrates the negative feedback response following a high-carbohydrate meal.
Diagram illustrating the negative feedback mechanism that regulates blood glucose levels after a high-carbohydrate meal. The figure shows elevated blood glucose triggering the pancreas to release insulin, which promotes glucose uptake by body cells, thereby lowering blood glucose levels. As glucose levels decline, the pancreas shifts to releasing glucagon, which signals the liver to convert glycogen into glucose and release it into the bloodstream. This feedback loop maintains glucose homeostasis. The figure emphasizes the dynamic hormonal regulation between insulin and glucagon.
Figure 11.9 Illustration of the Negative Feedback Mechanism Regulating Blood Glucose Levels After a High-Carbohydrate Meal. This diagram illustrates how blood glucose levels are regulated through a negative feedback loop. After a high-carbohydrate meal, blood glucose levels rise, prompting the pancreas to release insulin. Insulin facilitates the uptake of glucose by cells, lowering blood glucose levels. When glucose levels drop, the pancreas releases glucagon, which signals the liver to release stored glucose, maintaining homeostasis.

Insulin and glucagon responses during exercise

        During exercise, glucose uptake by muscles can increase significantly, ranging from 7- to 20-fold. Consequently, insulin concentration decreases during exercises of increasing intensity to conserve blood glucose for the exercising muscles. If insulin secretion were to increase during exercise, all tissues would uptake glucose more rapidly, potentially leading to hypoglycemia. Lower insulin concentrations during exercise favor the mobilization of glucose from the liver and free fatty acids (FFAs) from adipose tissues. This mobilization helps maintain plasma glucose concentrations during moderate-intensity and long-term exercise bouts.
        As plasma insulin decreases during exercise, glucagon levels increase. Secreted by the alpha cells of the islets of Langerhans, glucagon has effects opposite to those of insulin. In response to low plasma glucose concentrations, glucagon stimulates the mobilization of glucose from the liver, gluconeogenesis, and the release of FFAs from adipose tissues. These actions help spare blood glucose for use as fuel by the tissues. Thus, glucagon increases during exercise to favor the mobilization of FFAs from adipose tissue and glucose from the liver, maintaining plasma glucose concentrations for muscles that are using glucose at a higher rate.

Adrenal Glands

        The adrenal glands, located above the kidneys, are responsible for producing a variety of steroid and adrenal hormones. The gland consists of two sections: the inner adrenal medulla and the outer adrenal cortex. The adrenal medulla secretes epinephrine (E), norepinephrine (NE), and catecholamines, while the adrenal cortex secretes steroid hormones. These hormones play crucial roles in the body’s response to stress, including exercise, by regulating metabolism, cardiovascular function, and other physiological processes.
adrenalgland.png
Figure 11.10 The Location and Functions of the Adrenal Glands. The adrenal glands are located on top of each kidney. They produce essential hormones such as cortisol, aldosterone, and adrenaline, which help regulate metabolism, blood pressure, and the body’s response to stress. Photo credit (13).

Adrenal medulla and its hormones

        The adrenal medulla is regulated by the sympathetic nervous system, with approximately eighty percent of its hormonal secretion being epinephrine. Epinephrine has widespread effects on various systems, including the cardiovascular, respiratory, gastrointestinal, liver, muscle, and adipose tissues. Both epinephrine and norepinephrine are crucial for mobilizing substrates during exercise and are released in response to strong emotional stimuli as part of the “fight or flight” response. These hormones also play a significant role in regulating blood pressure and plasma glucose concentration.
        Epinephrine (E) and norepinephrine (NE) bind to adrenergic receptors on target tissues. These receptors are classified into two major classes: alpha adrenergic receptors (α) and beta adrenergic receptors (β), with their respective subgroups (α1, α2; β1, β2, and β3). E and NE operate via a secondary messenger mechanism and can have inhibitory or stimulatory effects depending on the receptor type. Different receptors alter cell activity by changing cyclic AMP or Ca++ concentrations.

Adrenal cortex and its hormones

        The adrenal cortex, the outer portion of the adrenal gland, secretes cholesterol-derived hormones, including mineralocorticoids (aldosterone), glucocorticoids (cortisol), androgens, and estrogens. Aldosterone is involved in maintaining Na+ and K+ concentrations in blood plasma, directly influencing Na+/H2O balance, plasma volume, and blood pressure. Aldosterone release can be triggered by decreases in plasma volume or increases in plasma K+ concentration. Elevated K+ levels stimulate aldosterone secretion, which then prompts the kidneys to actively transport K+.
        When plasma volume decreases, the kidneys secrete an enzyme called renin. Renin converts angiotensinogen in the plasma to angiotensin I, which is then converted to angiotensin II by angiotensin-converting enzyme (ACE) in the lungs. Angiotensin II is a potent vasoconstrictor and stimulates aldosterone release, increasing Na+ reabsorption in the kidneys. As water follows Na+ to balance osmolality, this process conserves water and increases blood plasma volume. During exercise intensities greater than 50% VO2max, renin, angiotensin, and aldosterone levels increase in parallel to maintain plasma concentration necessary for sweating and blood pressure regulation [3].
Diagram of the renin-angiotensin pathway, which regulates blood pressure and fluid balance. The figure begins with the kidneys detecting a drop in blood pressure and releasing renin. Renin converts angiotensinogen, produced by the liver, into angiotensin I. Angiotensin I is then converted into angiotensin II by angiotensin-converting enzyme (ACE), primarily in the lungs. Angiotensin II causes blood vessels to constrict, raising blood pressure, and stimulates the adrenal glands to release aldosterone. Aldosterone promotes sodium and water retention by the kidneys, further increasing blood volume and pressure. The figure emphasizes the sequential hormonal interactions and feedback involved in this regulatory system.
Figure 11.11 The Renin-Angiotensin Pathway. This pathway illustrates the steps involved in regulating blood pressure and fluid balance. When blood pressure drops, the kidneys release renin, which converts angiotensinogen from the liver into angiotensin I. Angiotensin I is then converted to angiotensin II by the angiotensin-converting enzyme (ACE) primarily in the lungs. Angiotensin II acts to constrict blood vessels, increasing blood pressure, and stimulates the release of aldosterone from the adrenal glands, which promotes sodium and water retention by the kidneys.

Cortisol and its role in metabolism

        Cortisol is the primary glucocorticoid secreted by the adrenal cortex, playing a crucial role in regulating plasma glucose levels during exercise and long-term fasting. Cortisol targets various tissues, including adipose and liver tissues. Upon secretion, cortisol inhibits glucose entry into tissues and promotes the breakdown of tissue proteins to release amino acids. These amino acids are then utilized by the liver to produce glucose through a process known as gluconeogenesis. Additionally, cortisol stimulates liver enzymes involved in gluconeogenesis. Cortisol also facilitates the mobilization of free fatty acids (FFAs) from adipose tissue, providing an alternative energy source. The release of cortisol is regulated by a negative feedback mechanism, ensuring that its levels remain balanced to meet the body’s metabolic demands. This regulatory process is depicted in Figure 11.12.
Diagram illustrating the effects of exercise and stressors on cortisol release and regulation. The figure shows how physical exercise, acting as a controlled stressor, stimulates the hypothalamic-pituitary-adrenal (HPA) axis. This leads to the release of cortisol from the adrenal glands. Cortisol facilitates substrate mobilization, including the breakdown of fats and proteins, and supports glucose availability for energy. The diagram emphasizes cortisol’s role in metabolic regulation during stress and physical activity, as well as the feedback mechanisms that modulate its release.
Figure 11.12 Effects of Exercise and Stressors on Cortisol Release and Regulation. This diagram illustrates how exercise and stressors influence cortisol release and its regulation. Exercise can act as a controlled stressor, initially increasing cortisol levels. Cortisol, produced by the adrenal glands, plays a crucial role in managing substrate mobilization and utilization.

Testes and Ovaries

        The most well-known hormones produced by the testes and ovaries are testosterone and estrogens, respectively. These hormones promote secondary sex characteristics, are crucial for establishing and maintaining reproductive function, and can influence exercise performance based on various metabolic and chronic factors. Androgens and estrogens also support prepubescent growth and female sex drive.
        Testosterone is secreted by the interstitial cells of the testes and is regulated by luteinizing hormone (LH), also known as interstitial cell-stimulating hormone (ICSH). LH release is controlled by a releasing hormone from the hypothalamus. Testosterone is both an anabolic and androgenic steroid, stimulating protein synthesis and causing changes during adolescence that lead to a high muscle-mass to fat-mass ratio. Studies have shown that plasma testosterone concentrations increase by 10-37% during prolonged submaximal work, maximal exercise, and endurance and strength training workouts [4][5]. While exercise-induced testosterone secretion was once thought to be the primary stimulus for muscle protein synthesis and hypertrophy, this effect varies individually and may only account for about 10% of changes [6]. Due to its muscle-building properties, testosterone and synthetic variants are among the most abused substances to enhance muscle mass and performance.
        Estrogens and progesterone are hormones with similar effects, secreted by the ovaries. Estrogens, including estradiol, estrone, and estriol, are responsible for breast development, female fat deposition, and other secondary sex characteristics. LH stimulates the production of androgens in the follicle, which are then converted to estrogens under the influence of follicle-stimulating hormone (FSH). Following ovulation, the luteal phase of the menstrual cycle begins, during which both estrogens and progesterone are produced by the corpus luteum. The effect of the menstrual cycle on exercise performance is still unclear, but current evidence suggests that anaerobic performance is not affected by the menstrual cycle phase [7]. Additionally, glucose-regulatory hormones appear to be unaffected by the menstrual cycle during prolonged exercise [8]. Studies also indicate no significant effects on VO2max, lactate production, plasma volume, risk of heat illness, heart rate, or ventilatory responses to exercise due to the menstrual cycle [9].
        Exercise-induced menstrual cycle irregularities, particularly in endurance, aesthetic, and weight-class athletes, can lead to chronically low estradiol levels, negatively impacting bone mineral content and increasing the risk of osteoporosis. Osteoporosis is common in athletes who experienced secondary amenorrhea (onset of amenorrhea after menarche) due to high volumes of exercise training. The prevalence of amenorrhea in college-aged women is 2-5%, but in collegiate runners, the incidence can range from 3-60% as training volume increases from less than 10 miles (16 km) to more than 68 miles (113 km) per week [10].
        A summary of the hormones discussed in this section, including their actions, stimuli, controlling factors, and the effects of acute and chronic exercise, is shown in Table 11.1.
Table 11.1 Summary of Endocrine Hormones: Actions, Secretion Control, Stimuli Factors, and Effects of Acute and Chronic Exercise Training. This table provides an overview of various endocrine hormones, detailing their primary actions, the factors controlling their secretion, the stimuli that influence their release, and the effects of both acute and chronic exercise training on these hormones.
Gland
Hormone
Action
Control Factors
Stimuli        
Acute Exercise Effect
Chronic Exercise Effect
Anterior pituitary
Growth Hormone (GH)
 
Growth, FFA mobilization, gluconeogenesis; decreases glucose uptake
GH-releasing hormone; somatostatin
Exercise; stress; low blood glucose
Increase
Attenuated response at same rate of work
Thyroid-stimulating hormone (TSH)
Increases T3 and T4 production and secretion
TSH-releasing hormone
Low plasma, T3 and T4
Increase
No known effect
Adrenocorticotrophic hormone (ACTH)
Increases cortisol synthesis and secretion
ACTH-releasing hormone
Stress; bone breaks; heavy exercise; burns
Increase
Attenuated response
Follicle-stimulating hormone (FSH); luteinizing hormone (LH)
Female: Estrogen and progesterone production and ovum development
Male: testosterone production and sperm development
Hypothalamic gonadotrophic-releasing hormone
Females: plasma estrogen and progesterone
Males: plasma testosterone
Firing of neurons in the hypothalamus
Small or no change
No known effect
Endorphins
Block pain in opiate receptors in the brain
ACTH-releasing hormone
Stress
Increases in exercise > or = 70% VO2max
Unknown
Posterior pituitary
Antidiuretic hormone (ADH) (vasopressin)
Decrease water loss at kidney; increases peripheral resistance
Hypothalamic neurons
Plasma volume; plasma osmolality
Increase
Attenuated response
Thyroid
Triiodothyronine (T3); thyroxine (T4)
Increase metabolic rate, mobilization of fuels, growth
TSH; plasma T3 and T4
Low T3 and T4
Increase in “free” T3 and T4
Increase turnover of T3 and T4 at same work rate
Calcitonin
Decreases plasma calcium
Plasma calcium
Elevated plasma calcium
Unknown
Unknown
Parathyroid hormone
Increase plasma calcium
Plasma calcium
Low plasma calcium
Increase
Unknown
Adrenal cortex
Cortisol
Increases gluconeogenesis, FFA mobilization, heart rate, stroke volume, and peripheral resistance
ACTH
Stress; bone breaks; heavy exercise; burns
Increases in heavy exercise; decreases in light exercise
Slight increase
Aldosterone
Increases potassium secretion and sodium reabsorption at kidney
Plasma potassium concentration and renin-angiotensin system
Low blood pressure, low plasma volume, elevated K+
Increase
Unchanged
Adrenal medulla
Epinephrine (E) (80%); norepinephrine (NE) (20%)
Increases glycogenolysis, FFA mobilization, heart rate, stroke volume, and peripheral resistance
Output of baroreceptors; glucose receptor in hypothalamus; brain and spinal centers
Low blood pressure and blood pressure; stress and emotion
Increase
Attenuated response
Pancreas
Insulin
Increases glucose amino acid, and FFA uptake into tissues
Plasma glucose and amino acid concentration; autonomic nervous system
Elevated plasma glucose and amino acid concentration; decreased E and NE
Decrease        
Attenuated response
Testes
Testosterone
Protein synthesis; secondary sex characteristics
FSH and LH (ICSH)
Increased FSH and LH
Small increase
Resting levels decreased
Ovaries
Estrogens and progesterone
Fat deposition; secondary sex characteristics; ovum development
FSH and LH
Increased FSH and LH
Small increase
Resting levels may be decreased in trained women

Endocrine Responses to Resistance Exercise

        Hormones play a crucial role in protein synthesis and degradation processes that are part of muscle adaptations to resistance exercise. Anabolic hormones promote tissue building and contribute to various aspects of muscle remodeling. These hormones include testosterone, insulin, insulin-like growth factors (IGFs), and thyroid hormone. These also aid in hypertrophy and inhibit catabolic hormones such as cortisol and progesterone that cause muscle protein breakdown. Resistance training induces significant hormonal changes essential for muscle adaptations. Changes in acute muscular force, power generation, tissue growth, and remodeling would not be possible without these hormonal changes. The short-term effects of resistance training on anabolic hormone release depend on the type of stimulus. Studies have shown that intensity, volume, the amount of muscle mass targeted, recovery, and training frequency are critical elements that stimulate muscle and tissue remodeling [11]. Long-term adaptations in these hormones are minimal compared to acute changes but are also related to the intensity and volume of training [12]. The main anabolic and catabolic hormones of interest during and following resistance training are discussed below.

Acute Hormonal Response to Resistance Training

The acute hormonal response to resistance training is more critical to tissue growth and remodeling than chronic changes in resting hormone concentrations. Anabolic hormones such as testosterone and growth hormone (GH) have been shown to elevate for 15-30 minutes post-resistance exercise when an adequate stimulus is achieved [13]. High volumes of training at moderate to high intensities, short rest intervals, and targeting large muscle groups produce the greatest acute hormonal elevations in testosterone, GH, and cortisol compared to low-volume, high-intensity protocols with long rest intervals. Testosterone targets include augmentation of hormonal mechanisms, such as stimulating GH and IGF-1, and interacting with receptors on neurons and neurotransmitter release. GH encourages muscle growth through protein synthesis and aids in energy generation by increasing free fatty acid mobilization and gluconeogenesis. Studies have shown inconsistent results in chronic resting levels of testosterone and GH, with most showing no change following long-term training protocols [14].

Insulin and Insulin-Like Growth Factor-1 (IGF-1)

        Insulin and IGF-1 are critical anabolic hormones for skeletal muscle growth. Insulin significantly affects muscle protein synthesis when adequate amino acids are available, helping to reduce protein catabolism. Without protein and carbohydrate supplementation, insulin concentrations decrease during acute resistance exercise as serum concentrations parallel changes in blood glucose levels. Research indicates that supplementation before or during resistance exercise is beneficial for maximizing protein synthesis and muscle hypertrophy.
Diagram showing the liver’s response to growth hormone (GH) stimulation. The figure illustrates GH binding to receptors on liver cells, triggering the production and release of insulin-like growth factor 1 (IGF-1). IGF-1 then enters circulation and promotes anabolic effects, including bone and muscle growth. The image emphasizes the endocrine signaling pathway linking GH to tissue development via hepatic IGF-1 production.
Figure 11.13 Growth Hormone Response in the Liver. The release of growth hormones stimulates the liver to produce insulin-like growth factor 1 (IGF-1), which promotes bone and muscle growth.

        IGFs are small polypeptide hormones secreted by the liver in response to GH-stimulated DNA synthesis. Their main role is to increase protein synthesis following resistance training, resulting in muscle hypertrophy. Recent evidence suggests that IGF-1 increases gene and protein expression due to the stretch and tension associated with resistance training. However, the response is delayed until GH-stimulated synthesis and secretion from the liver occur, with peak values not reached until 16-28 hours post-GH release [15]. Thus, the short-term responses of IGF-1 remain unclear. Chronically, training volume and intensity are important for chronic resting IGF-1 adaptations.

Catecholamines

Catecholamines are critical for force production, muscle contraction rate, energy liberation during exercise, and can affect other hormones such as testosterone. Acute exercise increases plasma concentrations of epinephrine (E), norepinephrine (NE), and dopamine. Significant elevations in plasma E and NE have also been observed before exercise, demonstrating an anticipatory or emotional response. Chronic adaptations to catecholamine release remain unclear, but it is suggested that training reduces the catecholamine response to resistance exercise.

Glucocorticoids

        Glucocorticoids are released from the adrenal cortex in response to the stress of resistance exercise, with cortisol accounting for 95% of this activity. Cortisol has catabolic functions that have greater effects on type II muscle fibers [16]. In peripheral tissues, cortisol stimulates lipolysis in adipose cells, increases protein degradation, and decreases protein synthesis in muscle cells, resulting in a greater release of lipids and amino acids into circulation. Several studies have shown significant elevations in cortisol and adrenocorticotropic hormone (ACTH) during acute resistance exercise in both men and women [17].
        A summary of the acute and chronic changes in important anabolic and catabolic hormone concentrations targeted during resistance exercise can be found in Table 11.2.
Table 11.2 Effects of Resistance Training on Acute and Chronic Changes in Notable Anabolic and Catabolic Hormones. This table summarizes the impact of resistance training on the acute and chronic changes in key anabolic hormones, such as testosterone and growth hormone, and catabolic hormones, such as cortisol. It highlights how different training protocols can influence hormone levels immediately after exercise and over prolonged periods, contributing to muscle growth, strength, and overall metabolic health.
Hormone
Acute response
Chronic response
Testosterone
Increase in men, no change or elevation in women
No change or inconsistent results
Growth Hormone
Increases in both sexes
No change
Cortisol
Increases in both sexes
No change or inconsistent results
IGF-1
No change
Increases with high volumes and intensities
Insulin        
Decreases without supplementation
No change
Catecholamines (Epinephrine, Norepinephrine, Dopamine)
Increase
Unclear
        Resistance training induces a complex array of hormonal changes that are crucial for muscle hypertrophy, force production, and energy liberation. Research indicates that the short-term effects of resistance training are influenced by factors such as intensity, volume, the amount of muscle mass targeted, recovery, and training frequency. These elements are essential for stimulating muscle and tissue remodeling. While long-term hormonal adaptations are minimal, they are closely related to the volume and intensity of training. Understanding these hormonal responses is key to optimizing resistance training outcomes.

Chapter Summary

        This chapter explored the intricate relationship between exercise and the endocrine system, emphasizing the roles of various hormones in maintaining homeostasis and facilitating muscle adaptations. Key points include:
  • Introduction to Exercise and Homeostasis: Exercise disrupts homeostasis, prompting acute and chronic changes regulated by the nervous and endocrine systems. Hormones play a vital role in mobilizing fuel, stimulating protein synthesis, and initiating muscle hypertrophy.
  • Categories of Hormones: Hormones are classified into amino acid derivatives, peptides/proteins, and steroid hormones. Their chemical makeup influences their transport in the blood and interaction with tissues.
  • Mechanisms of Hormone Action: Hormones modify cellular activity through altering DNA activity, membrane transport, and activating second messenger proteins. Examples include insulin’s role in glucose uptake and the G protein-coupled receptor mechanism.
  • Secretion of Hormones During Exercise: The chapter highlighted the endocrine glands most affected by exercise, including the hypothalamus, pituitary gland, thyroid, parathyroid glands, and pancreas. Hormonal regulation during exercise involves complex feedback mechanisms to maintain plasma glucose and calcium levels.
  • Adrenal Glands: The adrenal medulla and cortex secrete hormones like epinephrine, norepinephrine, cortisol, and aldosterone, which are crucial for stress response, metabolism, and maintaining plasma volume during exercise.
  • Testes and Ovaries: Testosterone and estrogens are essential for reproductive function and influence exercise performance. The chapter discussed their roles in muscle hypertrophy, secondary sex characteristics, and the impact of menstrual cycle irregularities on bone health.
  • Endocrine Responses to Resistance Exercise: Resistance training induces significant hormonal changes, particularly in anabolic hormones like testosterone, GH, insulin, and IGF-1, which are critical for muscle growth and remodeling. The chapter also covered the role of catecholamines and glucocorticoids in exercise. Resistance training elicits hormonal changes essential for muscle hypertrophy, force production, and energy liberation. Short-term effects depend on training intensity, volume, muscle mass targeted, recovery, and frequency, while long-term adaptations are minimal but related to training volume and intensity.
        Understanding these hormonal responses is key to optimizing exercise performance and achieving desired training outcomes.

Scholarly Questions

  1. How does exercise act as a stressor on the body, and what are the acute and chronic changes it induces?
  2. What roles do the nervous and endocrine systems play in maintaining homeostasis during exercise?
  3. What are the three classes of hormones based on their chemical makeup, and how does this affect their transport and interaction with tissues?
  4. How do steroid hormones differ from peptide/protein hormones in terms of their mechanism of action?
  5. Describe the process by which insulin facilitates glucose uptake in cells.
  6. Explain the G protein-coupled receptor mechanism and its significance in hormone action.
  7. Which endocrine glands are most affected by exercise, and what hormones do they secrete?
  8. How do changes in plasma volume and osmolality during exercise influence hormone secretion?
  9. What are the primary hormones secreted by the adrenal medulla and cortex, and what are their roles during exercise?
  10. How  does the renin-angiotensin-aldosterone system help maintain plasma volume during exercise?
  11. What are the functions of testosterone and estrogens in the body, and how do they influence exercise performance?
  12. Discuss the impact of menstrual cycle irregularities on bone health in female athletes.
  13. How do anabolic hormones like testosterone, GH, insulin, and IGF-1 contribute to muscle hypertrophy and remodeling during resistance training?
  14. What are the acute and chronic hormonal responses to resistance training, and how do they differ?
  15. Why is the acute hormonal response to resistance training more critical than chronic changes in resting hormone concentrations?
  16. How do catecholamines and glucocorticoids influence exercise performance and muscle adaptation?
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  13. Kraemer WJ, Ratamess NA, Hormonal Responses and Adaptations to Resistance Exercise and Training. Review Article. Sports Medicine, 2005. 35(4): p. 339-361. ↵
  14. Kraemer WJ, Ratamess NA, Hormonal Responses and Adaptations to Resistance Exercise and Training. Review Article. Sports Medicine, 2005. 35(4): p. 339-361. ↵
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  17. Kraemer WJ, Ratamess NA, Hormonal Responses and Adaptations to Resistance Exercise and Training. Review Article. Sports Medicine, 2005. 35(4): p. 339-361. ↵
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