Exercise Endocrinology

• Reading material concerns exercise endocrinology
• Fuel sources are both mobilized and utilized in a coordinated fashion
• Adipose tissue is stimulated to release more free fatty acids
• The liver is notified to create/release more glucose into the blood

Neuroendocrinology

• Involves a neuroendocrine system The endocrine system releases hormones
• The nervous system utilizes neurotransmitters
• Endocrine glands release chemical messengers (hormones) directly into the bloodstream
• Hormones alter the activity of tissues possessing receptors specific to them
• Binding initiates the action

Hormones

• Several classes of hormones exist, based on chemical makeup:
• Amino acid derivatives
• Peptides
• Proteins
• Steroids
• Chemical structure affects transport and effects on tissue

Blood Hormone Control

• A hormone's effect on a tissue is proportional to its concentration in the blood and the number of active receptors
• Concentration depends on:
• Rate of secretion from the gland
• Rate of metabolism or excretion
• Quality of transport proteins
• Changes in plasma volume

Hormone Secretion

• Rate of secretion depends on:
• Magnitude of input
• Whether the input is stimulatory or inhibitory
• Input is always a chemical like an ion, neurotransmitter, substance (e.g., glucose) or another hormone
• Hormone control is redundant with many inhibitors of secretion

Insulin Secretion Factors

• Plasma concentration is influenced by the rate of metabolism
• Inactivation can occur at or near the receptor or in the liver
• The kidneys also aid in hormone secretion

Transport Protein & Plasma Volume

• Some hormones require transport proteins in the blood, specifically steroid hormones
• Hormones must be "free" to exert an effect
• The amount of free hormone depends on the quality of the transport protein and the protein's capacity and affinity to bind hormone molecules
• Plasma volume changes occur with changes in body position, during exercise, and in response to heat
• Blood concentrates and elevates hormone concentration, enhancing hormone effects

Hormone-Receptor Interactions

• Hormones are carried to all tissues via circulation, but effects are only exerted on tissues with specific receptors
• Receptors are not static
• Downregulation decreases receptor number in response to high hormone concentration, diminishing the response for any given hormone concentration. Also the tissue becomes less sensitive
• Upregulation increases receptor number in response to low hormone concentration to enhance sensitivity
• Saturation occurs when all receptors are bound with a hormone, so increases in hormone concentration will have no effect
• Competition occurs when two hormones have a similar chemical shape and compete for binding, because receptors are specific to chemical shape

Hormone Action Mechanisms

• Hormones exert a response/effect in several ways:
• Altering DNA activity in the nucleus to initiate or suppress synthesis of a specific protein (Steroids)
• Activating special proteins called "second messengers"
• Altering membrane transport mechanisms (Insulin)

Altering Activity of DNA in the Nucleus

• Easily diffuses into the cell
• They bind to a receptor protein in the cytoplasm or nucleus
• In nucleus, hormones or hormone-receptor complex bind to hormone-responsive elements on DNA
• This activates genes that lead to mRNA synthesis, carrying codes from nucleus to cytoplasm where the protein is synthesized

Cyclic AMP “Second Messenger” Mechanism

• Hormone binds to receptor on cell surface
• This activates a G protein in the cell membrane and provides a link between the inside of cell and hormone-receptor complex on surface
• G protein activates adenylate cyclase, causing cyclic AMP formation
• Increased cyclic AMP concentration activates protein kinase A, which in turn activates response proteins to alter cellular activity

Ion Channel "Second Messenger” Mechanism

• Hormone binds to receptor on cell surface
• This activates a G protein in the cell membrane and provides a link between the inside of cell and hormone-receptor complex on surface
• G protein activates phospholipase C
• Phospholipid on membrane (PIP2) is hydrolyzed into IP3 (causing Ca++ release) and DAG
• Ca++ binds and activates calmodulin
• DAG activates protein kinase C, which activates proteins in the cell
• DAG and calcium effects work in concert with calmodulin effects

Membrane Transport

• A hormone binds to the receptor on the cell surface to activate carrier molecules in or near the membrane to facilitate the movement of substrates/ions into the cells
• Hormones are secreted from endocrine glands:
• Hypothalamus and pituitary glands
• Thyroid and parathyroid glands
• Adrenal gland
• Pancreas
• Testes and ovaries

Hypothalamus and Pituitary Gland

• The hypothalamus controls secretions from the pituitary gland and is located at the base of the brain and attached to it
• Anterior Pituitary Gland
• Hormone release is controlled via chemicals from the hypothalamus
• These chemicals stimulate/inhibit the release of specific anterior pituitary hormones
• Posterior Pituitary Gland
• Also controlled by hypothalamus - hormones go down axon to blood vessels in posterior pituitary and discharge into circulation

Anterior Pituitary Hormones

• Adrenocorticotropic hormone (ACTH)
• Follicle-stimulating hormone (FSH)
• Luteinizing hormone (LH)
• Melanocyte-stimulating hormone (MSH)
• Thyroid-stimulating hormone (TSH)
• Growth hormone (GH)
• Prolactin

Posterior Pituitary Hormones

• Oxytocin
• Antidiuretic hormone (ADH)

Growth Hormone

• Secretion is stimulated by exercise (most potent), sleep, stress, and low plasma glucose
• It stimulates the growth of all tissue through insulin-like growth factors (IGFs)
• Stimulates amino acid uptake, synthesis of new proteins, and long-bone growth
• It spares glucose
• GH release is controlled via negative feedback where GH and IGF concentration inhibit further GH release

GH Role

• Increases gluconeogenesis in liver
• Blocks glucose entry to adipose cell to favor fat mobilization

GH and Exercise

• GH is responsive to exercise and increases by about 2,000% at max
• It's greater in trained vs. untrained subjects so as adaptation to a fitness program increases the growth hormone output during intense exercise

GH and Performance

• GH increases protein synthesis and long-bone growth
• It's used to treat childhood dwarfism and by elderly individuals
• The effects for athletes are traditionally more adverse than beneficial, and there is minimal empirical evidence of performance improvement
• It could enhance recovery from exercise and has the potential for greater intensity training

Posterior Pituitary Gland: Antidiuretic Hormone (ADH)

• Reduces water loss (via urine output) to maintain plasma volume and results in increased water reabsorption from the renal tubules to capillaries
• Release is stimulated by high plasma osmolality and low plasma volume due to sweat loss without water replacement
• Osmoreceptors in the hypothalamus sense water concentration (osmolality) in the interstitial fluid
• High osmolality shrinks osmoreceptors, causing a neural reflex that releases ADH whereas low plasma volume initiates a reflex in the LA that releases ADH

Thyroid Gland

• Is stimulated by TSH to synthesize Triiodothyronin (T3) and Thyroxine (T4)
• T4 is released from thyroid in greater amounts, but converted to T3, which is more potent

Thyroid Hormones

• Central to establishing overall metabolic rate related to weight
• There is a latent period between T3 and T4 release and when their effects are observed
• T3-6-12 hours
• T4-2-3 days
• Have long lasting effects and are controlled by negative feedback
• During exercise, "free" concentration of hormones increases due to changes in transport protein's binding characteristics, which accelerates tissue uptake
• Calcitonin – thyroid hormone with minor role in Ca++ regulation

Parathyroid Gland/Hormone

• Releases PTH, the primary hormone involved in calcium regulation
• Happens in response to low plasma Ca++
• Bone releases Ca++ into plasma, increasing renal absorption

Adrenal Gland

• Adrenal Medulla involves Catecholamines, Epinephrine (EPI) and norepinephrine (NE)
• Adrenal Cortex involves Mineralcorticoids, Aldosterone and Glucocorticoids like Cortisol. Sex steroids include Androgens and Estrogens

Adrenal Medulla

• A part of the sympathetic nervous system, it secretes 80% Epinephrine and 20% Norepinephrine/
• They are both fast acting hormones and invoke the flight or fight response
• Bind to adrenergic receptors on targets depending of receptors such as Alpha (a) or Beta (β)

EPI and NE

• Appear and disappear quickly
• Maintain blood glucose during exercise
• Plasma levels increase during exercise
• There are decreased EPI and NE levels following training

Adrenal Cortex

• Secretes a variety of steroid hormones
• Mineralcorticoids are involved in maintenance of plasma Na+ and K+ concentration
• Glucocorticoids are involved in plasma glucose regulation
• Androgens and estrogens support prepubescent growth; androgens are associated with post-pubescent sex drive in women

Aldosterone

• An important regulator of Na+ and K+, and thus important for blood volume and blood pressure regulation
• Release controlled by K+ concentration and RAA system
• Decreased blood volume leads to decreased blood pressure which the kidney senses and increases renin secretion, converting angiotensinogen to angiotensin I
• Angiotensin I goes to the lungs and is converted to angiotensin II which stimulates the production/release of aldosterone

Cortisol

• Controls blood glucose during long-term fasting/exercise
• Promotes breakdown of tissue protein to form amino acids that undergo gluconeogenesis via Cori Cycle in liver
• Stimulates FFA mobilization from adipose tissue and liver enzymes involved in pathways leading to glucose synthesis
• Blocks glucose entry into tissues, forcing them to use more FFA as fuel

Pancreas

• Hormones released from pancreas play a role in blood glucose control
• Insulin secreted from B cells - most important hormone during absorptive state. It facilitates glucose movement from circulation to inside cells thus is stimulated by plasma amino acid/glucose concentration, and parasympathetic tone. But is inhibited by sympathetic outflow, EPI, & low plasma glucose
• Glucagon is secreted from α cells and has the opposite effect of insulin. It mobilizes glucose from hepatic glycogen stores, FFA from adipose tissue, and stimulates gluconeogenesis similar to cortisol & stimulated by low plasma glucose/EPI

Hormonal Control of Substrate Mobilization During Exercise

• Type and rate of substrate utilization depends upon intensity and duration of exercise
• High intensity means more carbohydrate usage
• Prolonged exertion means more fat usage

Muscle Glycogen Utilization

• Exercise intensity is related inversely to exercise duration; higher intensity means shorter duration
• With elevated intensity results in more quicker depletion

Control of Muscle Glycogen Utilization

• Plasma EPI is a powerful stimulator of glycogen breakdown
• Figure shows EPI concentration for a variety of intensities (VO2 max) and durations displayed in pattern similar to glycogen depletion

Control of Muscle Glycogen Utilization

• Receptor blockade has effect on the rate of glycogen depletion
• Studies investigated the effect of non-selective β-adrenergic receptor blockade
• The main point is that, there are other influential variables or players in the second messenger system
• The effects demonstrate that intracellular Ca++ plays a prominent role in glycogen usage/depletion

Blood Glucose Homeostasis During Exercise

• Exercise provides a significant challenge to blood glucose control mechanisms that requires the maintenance of Pglucose by four processes:
• Mobilization of liver glycogen, or hepatic glycogen stores
• Mobilize FFA from adipose tissue and spare plasma glucose
• New glucose is produced in hepatic gluconeogenesis such as amino acids, lactate, and glycerol
• Blood glucose entry into cells is forced primarily to muscle thus use of FFA is a fuel to maintain AND sustain work

Blood Glucose Homeostasis During Exercise

• Permissive and/or Slow Acting influences include:
  • Thyroxine
  • Cortisol
  • GH
• Fast Acting influences include:
  • EPI and NE
  • Insulin & Glucagon

Permissive & Slow Acting Hormones

• Thyroid hormones
• T3 and T4: responsible for basal metabolic rate allowing full effect
• They impact receptor sites directly on the cell and alter receptor affinity
• Mininal effect on FFA mobilization in absence of T3

Permissive & Slow Acting Hormones: Cortisol

• Stimulates fat from the ADipose tissue and mobilizes tissue protein to hepatic gluconeogenesis
• Decreases glucose utilization mainly because it appears cortisol increases glucose control in intense situations

Permissive & Slow Acting Hormones: Growth Hormone

• Decreases the rate of Glucose consumption and enhances hepatic glucose uptake. As well, increases drastically with trained or untrained levels
• A direct effect has a slow influence with exercises

Fast Acting Hormones

-Liver is crucial because it has the Glycogen that results mobilization of glucose (glycogenolysis), the key to Mobilization of fat that is derived from triglycerides, is an Interference with muscle to facilitate with the uptake. -Mobilization of the glucose from the liver. Has a connection to SNS activity that reflects on its effects in the plasma -A significant mobilization as a result of an action that occurs in the tissue and results due to interference with glucose with the uptake

Fast Acting Hormones

• Responsive to endurance Plasma Glucose with workload is constant. It is less influenced by given workloads
• Plasma EPI/NE at maximal level is greatly influenced as workloads increase.

Fast Acting Hormones

Insulin is highly influential as it increases glucose storage but has the opposite effect. While Glucagon has effects for glycogen breakdown therefore glucose rates are increased.