Endocrine Responses to Resistance Exercise chapter 3 Endocrine Responses to Resistance Exercise William J. Kraemer, PhD, CSCS, FACSM, FISSN, FNSCA Jakob L. Vingren, PhD, CSCS Barry A. Spiering, PhD, CSCS

Chapter Objectives Understand basic concepts of endocrinology. 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 Point It has been theorized that the endocrine system can be manipulated naturally with resistance training to enhance the devel-opment of various target tissues, thereby improving performance.

Section Outline Synthesis, Storage, and Secretion of Hormones

Key Term hormones: Chemical messengers that are synthesized, stored, and released into the blood by endocrine glands and certain other cells.

Glands of the Body Figure 3.1 (next slide) The principal endocrine glands of the body along with other glands that secrete hormones

Figure 3.1

Section Outline Muscle as the Target for Hormone Interactions

Muscle Cell Figure 3.2 (next slide) The muscle cell is a multinucleated cell in which each nucleus controls a region of the muscle protein (called a nuclear domain).

Figure 3.2

Section Outline Role of Receptors in Mediating Hormonal Changes

Lock-and-Key Theory for Hormonal Action Figure 3.3 (next slide) A schematic representation of the classic lock-and-key theory for hormonal action at the cell receptor level

Figure 3.3

Androgen Receptor Diagram Figure 3.4 (next slide) Diagram of a typical androgen receptor on the DNA element in the nucleus

Figure 3.4

Section Outline Steroid Hormones Versus Polypeptide Hormones Steroid Hormone Interactions Polypeptide Hormone Interactions

Steroid Hormones Versus Polypeptide Hormones There are two main categories of hormones: Steroid Polypeptide (or simply peptide)

Hormone Structure Figure 3.5 (next two slides) Structure of (a) a polypeptide hormone (growth hormone, 22 kDa) (b) a steroid hormone (testosterone)

Figure 3.5a

Figure 3.5b 20

Steroid Hormones Versus Polypeptide Hormones Steroid Hormone Interactions A steroid hormone passively diffuses across the sarcolemma of a muscle fiber. It binds with its receptor to form a hormone-receptor complex (H-RC). H-RC arrives at the genetic material in the cell’s nucleus and “opens” it in order to expose tran-scriptional units that code for the synthesis of specific proteins. (continued)

Steroid Hormones Versus Polypeptide Hormones Steroid Hormone Interactions (continued) RNA polymerase II binds to the promoter that is associated with the specific upstream regulatory elements for the H-RC. RNA polymerase II transcribes the gene by coding for the protein dictated by the steroid hormone. Messenger RNA (mRNA) is processed and moves into the sarcoplasm of the cell, where it is translated into protein.

Steroid Migration Figure 3.6 (next slide) The slide shows 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.

Figure 3.6

Steroid Hormones Versus Polypeptide Hormones Polypeptide Hormone Interactions Cyclic adenosine monophosphate-dependent (cyclic AMP-dependent) signaling pathway Cytokine-activated JAK/STAT signaling pathway Prototypical growth factor, mitogen-activated signaling pathway

Polypeptide Hormone Interaction Figure 3.7 (next slide) The slide shows typical polypeptide hormone (growth hormone in this example) 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. Tyr-P = tyrosinase related protein

Figure 3.7

Section Outline Heavy Resistance Exercise and Hormonal Increases

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

Section Outline Mechanisms of Hormonal Interactions

Mechanisms of Hormonal Interactions Interactions with receptors are greater when exercise acutely increases the blood concentrations of hormones. Receptors are less sensitive when the physiological function to be affected is already close to a genetic maximum, resting hormone levels are chronically elevated due to disease or exogenous drug use, and mistakes are made in exercise prescriptions.

Section Outline Hormonal Changes in Peripheral Blood

Hormonal Changes in Peripheral Blood Mechanisms contributing to changes in peripheral blood concentrations of hormones: Fluid volume shifts Tissue clearance rates Hormonal degradation Venous pooling of blood Interactions with binding proteins in the blood These mechanisms interact to produce certain concentrations of hormones in the blood, which influences the potential for interaction with receptors.

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

Section Outline Adaptations in the Endocrine System

Adaptations in the Endocrine System Examples of the potential types of adaptation with resistance exercise: Amount of synthesis and storage of hormones Transport of hormones via binding proteins Time needed for the clearance of hormones through liver and other tissues Amount of hormonal degradation that takes place over a given period of time How much blood-to-tissue fluid shift occurs with exercise stress How many receptors are in the tissue

Section Outline Primary Anabolic Hormones Testosterone Growth Hormone Free Testosterone and Sex Hormone–Binding Globulin Testosterone Responses in Women Training Adaptations of Testosterone Growth Hormone Efficacy of Pharmacological Growth Hormone Growth Hormone Responses to Stress Growth Hormone Responses in Women Training Adaptations of Growth Hormone (continued)

Section Outline (continued) Primary Anabolic Hormones Insulin-Like Growth Factors Exercise Responses of Insulin-Like Growth Factors Training Adaptations of Insulin-Like Growth Factors

Primary Anabolic Hormones There are three primary hormones involved in muscle tissue growth and remodeling: Testosterone Growth hormone (GH) Insulin-like growth factors (IGFs)

Primary Anabolic Hormones Testosterone The primary androgen hormone that interacts with skeletal muscle tissue Effects on muscle tissue: GH responses that lead to protein synthesis, increased strength and size of skeletal muscle, increased force production potential and muscle mass Diurnal variations Men: Exercise later in the day is more effective for increasing overall testosterone concentrations over an entire day. Women: There are lower concentrations and little variation during the day.

Biosynthesis of Testosterone From Cholesterol Figure 3.8 (next slide) The series of chemical reactions in the biosynthesis of testosterone from cholesterol

Figure 3.8

Key Point Large muscle group exercises result in acute increased serum total testosterone concentrations in men.

Primary Anabolic Hormones Testosterone Free Testosterone and Sex Hormone–Binding Globulin A higher total (bound) testosterone level allows for the potential of more free testosterone. The free hormone hypothesis states that only the free hormone interacts with target tissues. Testosterone Responses in Women Women have 15- to 20-fold lower concentrations of testosterone than men do, and if acute increases occur after a resistance training workout, they are small. Training Adaptations of Testosterone

Serum Testosterone Responses to Exercise Figure 3.9 (next slide) Male (green bars) and female (gold bars) serum testosterone responses to two exercise programs: (a) a protocol entailing eight exercises using 5RM and 3-minute rest periods between sets and exercises (b) a program that called for eight exercises using 10RM and 1-minute rest periods between sets and exercises (the total work for the second protocol was higher) * = significantly above preexercise levels + = significantly above the other group

Figure 3.9 Reprinted, by permission, from Kraemer et al., 1990.

Primary Anabolic Hormones Growth Hormone Secreted by the pituitary gland Interacts directly with target tissues, which include bone, immune cells, skeletal muscle, fat cells, and liver tissue Regulated by neuroendocrine feedback mechanisms and mediated by secondary hormones GH release patterns altered by age, gender, sleep, nutrition, alcohol consumption, and exercise

Growth Hormone Cybernetics and Interactions Figure 3.10 (next slide) Diagram of growth hormone cybernetics and interactions

Figure 3.10

Primary Anabolic Hormones Growth Hormone Efficacy of Pharmacological Growth Hormone Pharmacological use of GH has unknown and unpredictable results. Growth Hormone Responses to Stress GH responds to exercise stressors, including resistance exercise. GH response depends on load, rest, and volume of exercise.

Primary Anabolic Hormones Growth Hormone Growth Hormone Responses in Women GH concentrations and responses to exercise vary with menstrual phase. Women have higher blood levels of GH than do men. Training Adaptations of Growth Hormone There is little change in single measurements of resting GH concentrations in resistance-trained individuals. Training-related changes in GH include a reduction in GH response to an absolute exercise stress and alterations in GH pulsatility characteristics.

Key Point Growth hormone is important for the normal development of a child and appears to play a vital role in adapting to the stress of resistance training. However, GH injections result in a wide variety of secondary effects not related to changes in muscle size or strength and can, in fact, result in hyper-trophy with less force production than occurs with exercise-induced hypertrophy.

Primary Anabolic Hormones Insulin-Like Growth Factors Exercise Responses of Insulin-Like Growth Factors Insulin-like growth factor I (IGF-I) is most studied because of its role in protein anabolism. Exercise results in acute increases in blood levels of IGF-I.

Insulin-Like Growth Factor I and Exercise Figure 3.11 (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 (i.e., Mass Fuel) before and during the 1-hour recovery period †p < .05 from corresponding placebo value

Figure 3.11 Adapted, by permission, from Kraemer et al., 1998.

Primary Anabolic Hormones Insulin-Like Growth Factors Training Adaptations of Insulin-Like Growth Factors Changes in IGF-I appear to be based on the starting concentrations before training. If basal concentrations are low, IGF-I increases. If basal concentrations are high, there is no change or it decreases.

Section Outline The Adrenal Hormones Cortisol Catecholamines Role of Cortisol Resistance Exercise Responses of Cortisol Catecholamines Role of Catecholamines Training Adaptations of Catecholamines

The Adrenal Hormones Cortisol Role of Cortisol Catabolic effects Converts amino acids to carbohydrates, increases the level of enzymes that break down proteins, and inhibits protein synthesis Resistance Exercise Responses of Cortisol Cortisol increases with resistance exercise. Training may reduce the negative effects of this increase. Vast differences are observed in the physiological role of cortisol in acute versus chronic responses.

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 levels of cortisol may have adverse catabolic effects, acute increases may contribute to the remodeling of muscle tissue.

The Adrenal Hormones Catecholamines Role of Catecholamines Increase force production via central mechanisms and increased metabolic enzyme activity Increase muscle contraction rate Increase blood pressure Increase energy availability Increase blood flow Augment secretion rates of other hormones, such as testosterone Training Adaptations of Catecholamines

Key Point Training protocols must be varied to allow the adrenal gland to engage in recovery processes and to prevent the secondary responses of cortisol, which can have negative effects on the immune system and protein structures.

Section Outline Other Hormonal Considerations

Other Hormonal Considerations Many other hormones create an optimal environment in which the primary hormonal actions can take place. Insulin, thyroid hormones, and beta-endorphins affect growth, repair, and exercise stress mechanisms. Improvements in insulin resistance with resistance training may reflect only an acute effect from the most recent exercise session. Researchers have found slight, nonsignificant decreases in serum concentrations of total and free thyroxine after 20 weeks of resistance training.