Muscle Hypertrophy and Anabolic Agents I

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Muscle Hypertrophy and Anabolic Agents I

• Lecture 20

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Muscle Anatomy

• Muscles are made up of
• bundles of individual fibers.
• Each fiber is a single
• elongated cell with a
• nucleus, mitochondria,
• endoplasmic reticulum, etc.
• Muscle cells are subdivided
• into myofibils composed of
• actin and myosin filaments
• linked in series in units
• called sarcomeres.
• Stimulus by motor neuron
• causes actin and myosin to
• interact sarcomeres shorten
• and produce force

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Muscle Anatomy (continued)

• 3 main types of muscle fibers
• Type I slow contraction, small, low
• glycogen and CP, many fat droplets
• and mitochondria, fatigue-resistant.
• Type IIa fast, intermediate size, high
• glycogen and CP, pretty rich in
• mitochondria, less fatigue-resistant
• Type IIb fast, large, high in glycogen
• and CP, few mitochondria, not
• fatigue-resistant.

Fat droplet
Mitochondria
Type I Fibers
Type IIb Fibers
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• All muscles
• contain a mix of
• fiber types.
• Muscles that show
• large gains in size
• with training
• usually have a
• fairly high of
• Type-II fibers (e.g.
• gastrocnemius vs.
• soleus).

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Muscle Anatomy and Training

• What are the stimuli for hypertrophy?
• 1. nutritional (energy balance, protein)
• 2. hormonal (testosterone, insulin, growth
  hormone)
• 3. stress (active training, passive stretch)
• Most trainable fibers are Type-IIa.
• After training they take on
• characteristics more like Type I or Type
• IIb depending on type of training.

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Muscle Anatomy and Training

• Fibers most sensitive to hypertrophy are
  Type-IIb.
• This explains why muscle hypertrophy occurs in
• response to stress of high force (resistance
• training). These fibers are only used when rate
  of
• force production is high.
• There is huge individual variation in hypertrophy
  
• response to training.

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Muscle Hypertrophy

• Hypertrophy increasing muscle size. Hypertrophy
• refers to increase in both the cross-sectional
  area of
• the muscle (more myofibrils) and increase in
  length
• of the muscle (more sarcomeres per myofibril).
• Does the number of muscle fibers increase
• (hyperplasia)?

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Hyperplasia?
HYPERTROPHY
HYPERPLASIA
VS.
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Muscle Hypertrophy

• Hypertrophy increasing muscle size. Hypertrophy
• refers to increase in both the cross-sectional
  area of
• the muscle (more myofibrils) and increase in
  length
• of the muscle (more sarcomeres per myofibril).
• Does the number of muscle fibers increase
• (hyperplasia)? Yes in some animals (e.g. cats)
  but
• this does not seem to be a mechanism of
  hypertrophy
• (ADULT) humans.

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Satellite Cell Repair
Hawke et al. 2001
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Muscle Hypertrophy

• Fibers do split as they get larger to maintain a
• minimal surface area to volume ratio.
• This splitting is beneficial because if volume
• increases more than surface area diffusion
• distance will increase and access to oxygen and
• other compounds might be limited.
• Splitting is not considered hyperplasia
• because the fiber shares nuclei.

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• The combined
• effects of nutrients,
• hormonal environment
• and mechanical load
• (training) are
• manifested by
• changes in both gene
• transcription and
• mRNA translation to
• increase myofibrillar
• protein content in the
• muscle cell

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Muscle Hypertrophy and Strength

• Force generating capacity in muscles depends on
• cross-sectional area. As area increases so does
• capacity to generate force (strength).
• Relationship is not 11 however.
• Strength increases at a faster
• rate than area (e.g. a 10
• increase in area results in a
• 30 increase in strength).
• This, in reverse, is a major problem in the
  elderly.
• They lose muscle mass and small decline in muscle
  
• size big decline in strength.

X
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Metabolic cost of muscle

• Besides obvious advantages of having more muscle
• mass in terms of strength - larger muscle mass
• helps with weight management.
• Muscle tissue consumes a lot of energy (high
• maintenance) and basal metabolic rate (energy
• required for basic life function) is directly
• proportional to muscle mass.
• More muscle mass higher basal metabolic rate
• more energy expended per day require more
• energy to maintain the same weight.

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Muscle Building Nutrition

• To gain muscle tissue it is necessary to create
  an
• anabolic environment. Nutritionally, creating
  that
• anabolic environment requires positive energy
• balance (more energy in than out).
• How much more energy in than out? This is the
• question b/c energy surplus also increases body
  fat
• Competitive (natural) body builders know this and
  
• incorporate 2 general phases
• 1. gain muscle and some fat (minimal if possible)
• 2. lose fat and some muscle (minimal if possible)

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The million dollar question

• How to minimize the fat gain while
• maximizing muscle gain?
• Maintain energy balance in state sufficient to
• gain muscle while minimizing fat gain
• 2. Hard resistance training
• 3. Incorporation of cardiovascular training into
  routine
• 4. Manipulation of the hormonal environment
• (nutritionally and pharmacologically)

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ANABOLIC STEROIDS
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STEROIDS FOR SALE!
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Steroid Hormones

• Steroids are a group of
• chemical messengers
• that are synthesized
• from cholesterol. Since
• steroids are fat soluble,
• they are membrane
• permeable and often act
• directly on the nucleus
• of the cell. As you can
• see by the structures to
• the right, many of the
• sex hormones have
• similar structures.

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Ganong, 1995
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Testosterone

• Testosterone contributes to male
• sex characteristics including
• muscle growth. Most testosterone
• is produced in the testes (95)
• remainder is produced by the
• adrenal glands. Testosterone
• has both anabolic (muscle building) effects as
  well as
• androgenic (masculinizing) effects.

Anabolic steroids mimic the actions of
testosterone. Anabolic steroids are used
medically to treat male patients with low levels
of testosterone as well as muscle-wasting
diseases. First used during WWII to help
malnourished POWs regain weight and strength.
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Athletes and Androgens

• Athletes have used anabolic agents to enhance
• performance for 50 years. The goal is to maximize
  
• anabolic actions (incr. strength and muscle mass)
  
• while minimizing androgenic effects.
• Testosterone is classified as a drug and requires
  a
• prescription to obtain. It must be injected for
• maximal effect. Banned by
• most athletic bodies
• (USOC, NCAA, etc)

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• Testosterone

(5-alpha reductase)
(aromatase)
DHT Estradiol
Responsible for male secondary sex
characteristics 3 times as androgenic as
testosterone, yet only 50 as anabolic
Responsible for female secondary sex
characteristics
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Ganong, 1995
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Are steroids effective?

• Bhasin et al. Effects of a supraphysiological
  dose of
• testosterone on muscle size and strength in
  healthy
• men. NEJM 1996.
• 600mg testosterone enanthate given for 10 weeks
• Weight-trained drug group gain in LBM of 13.6
  lbs
• Untrained drug group gain in LBM of 6 lbs
• Considerable strength gains reported from both
• trained and untrained drug groups
• No noticeable side effects reported by
  subjects.
• HOWEVER, this tells us nothing about the long
  term
• effects. Anabolic steroids reduce HDL, increase
  LDL

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Muscle Quality?
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AAS and HIV
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Orals vs Injectables

• There are two types of anabolic steroids orals
  and
• injectables. Besides the obvious differences in
• delivery method, orals have much shorter
  half-lives
• than injectables. The half-life of most orals is
  3-5
• hours. The main consequences of the short
  half-life
• is that (a) they must be taken much more
  frequently
• than injectables (b) they are designed to
  withstand
• the digestive system as well as a trip through
  the
• liver and thus must be taken in larger doses than
  
• injectables.

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• Often oral steroids are methylated to decrease
• degradation as they pass through the liver.
• As a consequence, such drugs alter liver
• enzyme levels and can cause hepatoxicity.
• Methylation may also increase aromatization to
• estrogen.
• Injectables tend to have longer half-lives
• (increased serum testosterone levels may
• last up to 14 days). For this reason athletes
• tend not to take injectable steroids before
• competition because they are easy to detect.

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WELL, IF WE PUT MORE BUILDING BLOCKS IN, MAYBE
WE WILL MAKE MORE NATURAL TESTOSTERONE...
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Prohormones

• Prohormones are marketed to provide a raw
• material that the bodies own metabolic machinery
  
• can convert to testosterone.
• Are prohormones
• safer? If so, are
• they effective?

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IOC BANNED SUBSTANCES

• STIMULANTS
• NARCOTICS
• DIURETICS etc
• PEPTIDE HORMONES
• HCG LH HGH ACTH IGF-1
• ANABOLIC AGENTS
• DHT ANDRO DHEA TESTOSTERONE ETC
• TESTOSTERONE/EPITESTOSTERONE gt 61

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• Studies from Doug Kings lab at Iowa State show
  that
• DHEA does not increase testosterone or strength
• compared with placebo (but no increase in
  estrogen)
• 2. Androstenedione does increase testosterone but
  
• also increases estradiol. No impact on strength
  
• compared with placebo.
• BUT this study was criticized b/c subjects were
  not
• weight trained. Other studies done after this one
  
• suggest that androstenedione supplementation DOES
  
• raise testosterone levels and increase gain of
  muscle
• mass relative to placebo

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DO PRO-HORMONE SUPPLEMENTS WORK?

• ? andro/DHEA
• No ? serum T
• ? estrogens
• ? good cholesterol
• No ? from trained/no supp

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From bodybuildingforyou.com
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REAL WORLD VS RESEARCH
Serving Size 1 packet Servings Per Box
30Whole Pituitary 100mg Lyophilized Pineal
250mcgHypothalmus 100mg Orchic Powder
100mgL-Glutamine 150mg L-Tyrosine
100mgL-Lysine 100mg L-Arginine
100mgL-Ornithine 100mg Glycine
600mg4-Androstenediol 25mg 5-Androstenediol
25mgNor-4-AndroDione 25mg Nor-4-AndroDiol 25mg

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Cessation of Steroid Use
In order to understand the physiological
consequences of stopping steroid use here is a
brief review of the Hypothalamic-Pituitary-Testic
ular Axis (HPTA) hypothalamus ? GnRH
? anterior pituitary ? LH and FSH
? testes
? testosterone
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Cessation of Steroid Use (contd)
When using anabolic agents, high androgen levels
exert negative feedback on the hypothalamus and
decrease the rate at which GnRH is produced. The
lower GnRH levels reduce the amount of
endogenous testosterone produced and if steroid
use stops it takes a while for the body to
reequilibrate its own testosterone
production. hypothalamus ? GnRH
? anterior pituitary ? LH and FSH
? testes ?
testosterone
inhibition
inhibition
estrogen
Androgen use