Endocrine Responses to Resistance Exercise chapter 4 Endocrine Responses to Resistance Exercise William J. Kraemer, PhD, Jakob L. Vingren, PhD, and Barry A. Spiering, PhD

Chapter Objectives Understand basic concepts of endocrinology, including what hormones are and how they interact with each other and target tissues Explain the physiological roles of anabolic hormones Describe hormonal responses to resistance exercise Develop training programs that demonstrate an understanding of human endocrine responses

Key Terms hormones: Chemical messengers that are synthesized, stored, and released into the blood by endocrine glands and certain other cells. endocrine glands: Body structures specialized for releasing hormones into the blood.

Synthesis, Storage, and Secretion of Hormones Figure 4.1 (next slide) The principal endocrine glands of the body along with other glands that secrete hormones

Figure 4.1

Muscle as the Target for Hormone Interactions Hormones are intimately involved with protein synthesis and degradation mechanisms that are part of muscle adaptations to resistance exercise. This includes both anabolic (promote tissue building) and catabolic (degrade cell proteins) hormones.

Roles of Receptors in Mediating Hormonal Changes Lock-and-key theory Figure 4.2 (next slide) A schematic representation of the classic lock-and-key theory for hormonal action at the cell receptor level

Figure 4.2

Roles of Receptors in Mediating Hormonal Changes The inability of a hormone to interact with a receptor is called downregulation. Alterations to a receptor’s binding characteristics or the number of receptors can be as dramatic in adaptation as the release of increased amounts of hormone from an endocrine gland.

Categories of Hormones Steroid hormone interactions Fat soluble and passively diffuse across the cell membrane Figure 4.3 (next slide) Typical steroid migration into a target cell by either testosterone in skeletal muscle or dihydrotestosterone in sex-linked tissues. Only one hormone pathway (testosterone or dihydrotestosterone) is targeted for one cell, but the two are shown together in this diagram. Each has different physiological outcomes.

Figure 4.3

Categories of Hormones Polypeptide hormone interactions Made of chains of amino acids Examples: growth hormone and insulin Figure 4.4 (next slide) Typical polypeptide hormone interaction with a receptor via the cytokine-activated JAK/STAT signaling pathway Although the hormone binds to an external receptor, a secondary messenger (STAT) is activated that can enter the cell nucleus.

Figure 4.4

Categories of Hormones Amine hormone interactions Synthesized from the amino acid tyrosine (e.g., epinephrine, dopamine) or tryptophan (serotonin) Bind to membranes via secondary messengers Not regulated by negative feedback

Heavy Resistance Exercise and Hormonal Increases Hormones are secreted before, during, and after the resistance exercise bout due to the physiological stress of resistance exercise. As few as one or two heavy resistance exercise sessions can increase the number of androgen receptors in the muscle.

Key Point The specific force produced in activated fibers stimulates receptor and membrane sensitivities to anabolic factors, including hormones, which leads to muscle growth and strength changes.

Mechanisms of Hormonal Interactions The combination of many different mechanisms is thought to stimulate exercise-induced hypertrophy. Molecular signaling including hormones is involved with this process. This signaling is influenced by neural factors that provide important signals to the skeletal muscle and thus can augment anabolic processes.

Hormonal Changes in Peripheral Blood Peripheral concentrations of hormones in the blood do not indicate the status of the various receptor populations or the effects of a hormone within the cell. It is typically assumed, however, that large increases in hormone concentration indicate higher probabilities for interactions with receptors. (continued)

Hormonal Changes in Peripheral Blood (continued) Physiological mechanisms that contribute to changes in peripheral blood concentrations of hormones with exercise: Circadian pattern Fluid volume shifts Tissue clearance rates Venous pooling of blood Hormone interactions with binding proteins

Key Point Hormone responses are tightly linked to the characteristics of the resistance exercise protocol.

Adaptations in the Endocrine System Examples of the types of adaptations that are possible: Amount of synthesis and storage of hormones Time needed for clearance of hormones through liver and other tissues How many receptors are in the tissue Changes in the contents of the secretory cells in a gland Degree of interaction with the cell nucleus

Primary Anabolic Hormones Testosterone Heavy resistance training using one or two repetitions in low volume, which may not cause any changes in testosterone concentrations after a workout, could potentially still increase the absolute number of receptors and thus binding sites available to testosterone. This effect on receptors has yet to be fully elucidated.

Key Point Large muscle group exercises using an adequate volume of total work result in acute increased total testosterone concentrations in men.

Primary Anabolic Hormones Testosterone Exercise variables that can increase serum testosterone concentrations: Large muscle group exercises (deadlift, squats) Heavy resistance (85-95% of 1RM) Moderate to high volume of exercises Short rest intervals (30 seconds to 1 minute) Two years or more of resistance training experience (continued)

Primary Anabolic Hormones (continued) Testosterone Free testosterone and sex hormone–binding globulin Free testosterone accounts for only 0.5% to 2% of total testosterone; thus higher total testosterone concentration allows for more free testosterone. Heavy resistance exercise (e.g., six sets of 10 repetitions at 80% of 1RM) can acutely increase free testosterone in men and women, although the increase is much smaller for women. (continued)

Primary Anabolic Hormones (continued) Testosterone Responses in women Women have about 15- to 20-fold lower concentrations of circulating testosterone than men do. The testosterone concentration can vary substantially between individual women, as some women secrete higher concentrations of adrenal androgens. (continued)

Primary Anabolic Hormones (continued) Figure 4.5 (next slide) Responses to six sets of squats at 80% of 1RM with 2 minutes rest between sets (a) Total testosterone (b) Free testosterone in response * Indicates a significant increase from preexercise values. # Indicates a significant difference from women at the corresponding time point.

Figure 4.5(a)

Figure 4.5(b)

Primary Anabolic Hormones Testosterone Training adaptations Testosterone increases in response to the demands of an exercise protocol, and then the receptors either increase binding to use the elevated testosterone or they do not due to a lack of need for the signal to increase muscle-related metabolism. Other receptors on other target tissues (e.g., nervous, satellite cells) may be more affected at certain time points in training, depending on the window of adaptation available in the target tissues. (continued)

Primary Anabolic Hormones (continued) Growth hormone Important for the normal development of a child Appears to play a vital role in adapting to the stress of resistance training Figure 4.6 (next slide) Diagram of growth hormone cybernetics and interactions

Figure 4.6

Primary Anabolic Hormones Growth hormone Main physiological roles of GH and its superfamily: Decreases glucose utilization Increases protein synthesis Increases collagen synthesis Stimulates cartilage growth Enhances immune cell function Increases lipolysis (fat breakdown)

Key Point Growth hormone release is affected by the type of resistance training protocol used, including the duration of rest period. Short rest period types of workouts result in greater serum concentrations compared to long rest protocols of similar total work; however, at present it is not clear how the various molecular forms (e.g., aggregates and splice variants) or types of GH are affected by rest period duration.

Primary Anabolic Hormones Growth hormone Responses in women Hormone concentrations and hormone responses to exercise vary with menstrual phase. The mechanisms of this variation are unclear. (continued)

Primary Anabolic Hormones (continued) Growth hormone Training adaptations It appears that GH concentrations need to be measured over longer time periods (2-24 hours) to show whether changes occur with resistance training. The area under the time curve, which includes an array of pulsatile effects, tells whether changes in release have occurred. (continued)

Primary Anabolic Hormones (continued) Exercise responses of insulin-like growth factor Figure 4.7 (next slide) Responses of insulin-like growth factor I to a multiple-set, heavy resistance exercise protocol on three consecutive days with and without nutritional supplementation of protein-carbohydrate before and during the 1-hour recovery period

Figure 4.7

Primary Anabolic Hormones Training adaptations of insulin-like growth factor Probably reflected in a variety of mechanisms related to type of IGFs, release, transport, and receptor interaction. Interaction with other anabolic hormones cannot be ignored, as these often target the same outcome. Adaptations to heavy resistance training of IGF-I in the various tissues still require further investigation. (continued)

Adrenal Hormones Cortisol Exerts its major catabolic effects by stimulating the conversion of amino acids to carbohydrates, increasing the level of proteolytic enzymes (enzymes that break down proteins), inhibiting protein synthesis, and suppressing many glucose-dependent processes such as glycogenesis and immune cell function. Has a greater effect on Type II fibers than Type I fibers. (continued)

Adrenal Hormones (continued) Cortisol Resistance exercise responses Responds to resistance exercise protocols that create a dramatic stimulus to anaerobic metabolism. Increases in cortisol might not have negative effects in men after a period of training to which the body has adapted; adaptation “disinhibits” cortisol at the level of the testis, thereby maintaining testosterone’s primary influence on its nuclear receptors.

Key Point Resistance exercise protocols that use high volume, large muscle groups, and short rest periods result in increased serum cortisol values. Though chronic high concentrations of cortisol may have adverse catabolic effects, acute increases still contribute to the remodeling of muscle tissue and maintenance of blood glucose.

Adrenal Hormones Catecholamines Roles Increase force production via central mechanisms and increased metabolic enzyme activity Increase muscle contraction rate Increase blood pressure Increase energy availability Increase muscle blood flow (via vasodilation) Augment secretion rates of other hormones, such as testosterone (continued)

Adrenal Hormones (continued) Catecholamines Training adaptations Heavy resistance training has been shown to increase the ability of an athlete to secrete greater amounts of epinephrine during maximal exercise. Because epinephrine is involved in metabolic control, force production, and the response mechanisms of other hormones (such as testosterone, GHs, and IGFs), stimulation of catecholamines is probably one of the first endocrine mechanisms to occur in response to resistance exercise.

Other Hormonal Considerations Hormones such as insulin, thyroid hormones, and beta-endorphin have been implicated in growth, repair, pain analgesia, and exercise stress mechanisms; unfortunately, few data are available concerning their responses and adaptations to resistance exercise or training.