Transcript Muscle Hypertrophy And Anabolic Agents I

Muscle Hypertrophy and
Anabolic Agents I
Lecture 20
Muscles are made up of
bundles of individual fibers.
Each fiber is a single
elongated cell with a
nucleus, mitochondria,
endoplasmic reticulum, etc.
Muscle Anatomy
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
Muscle Anatomy (continued)
3 main types of muscle fibers
Fat
droplet
Type I: slow contraction, small, low
glycogen and CP, many fat droplets
and mitochondria, fatigue-resistant.
Mitochondria
Type I Fibers
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.
Type IIb Fibers
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).
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.
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.
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)?
Hyperplasia?
HYPERTROPHY
VS.
HYPERPLASIA
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.
Satellite Cell Repair
Hawke et al. 2001
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.
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
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 1:1 however.
Strength increases at a faster
strength
rate than area (e.g. a 10%
increase in area results in a
30% increase in strength).
X
cross-sectional area
This, in reverse, is a major problem in the elderly.
They lose muscle mass and small decline in muscle
size = big decline in strength.
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.
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)
The million dollar question…
How to minimize the fat gain while
maximizing muscle gain?
1. 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)
ANABOLIC STEROIDS
“STEROIDS FOR SALE!”
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.
Ganong, 1995
Testosterone contributes to male
Testosterone
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 POW’s regain weight and strength.
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)
Testosterone
(5-alpha reductase)
DHT
Responsible for male
secondary sex
characteristics
3 times as androgenic
as testosterone, yet
only 50% as anabolic
(aromatase)
Estradiol
Responsible for female
secondary sex
characteristics
Ganong, 1995
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
Muscle Quality?
AAS and HIV
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.
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.
WELL, IF WE PUT MORE BUILDING
BLOCKS IN, MAYBE WE WILL MAKE MORE
“NATURAL” TESTOSTERONE...
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?
OH
Testosterone
O
OH
Testosterone
O
IOC BANNED SUBSTANCES
STIMULANTS
NARCOTICS
DIURETICS etc
PEPTIDE HORMONES
» HCG; LH; HGH; ACTH; IGF-1
ANABOLIC AGENTS
» DHT; ANDRO; DHEA; TESTOSTERONE ETC
» TESTOSTERONE/EPITESTOSTERONE > 6:1
Studies from Doug Kings lab at Iowa State show that:
1. 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
DO PRO-HORMONE
SUPPLEMENTS WORK?
 andro/DHEA
» No  serum T
»  estrogens
»  good cholesterol
» No  from trained/no supp
From bodybuildingforyou.com:
REAL WORLD VS RESEARCH
Serving Size: 1 packet
Whole Pituitary: 100mg
Hypothalmus: 100mg
L-Glutamine: 150mg
L-Lysine: 100mg
L-Ornithine: 100mg
4-Androstenediol: 25mg
Nor-4-AndroDione: 25mg
Servings Per Box: 30
Lyophilized Pineal: 250mcg
Orchic Powder: 100mg
L-Tyrosine: 100mg
L-Arginine: 100mg
Glycine: 600mg
5-Androstenediol: 25mg
Nor-4-AndroDiol: 25mg
Cessation of Steroid Use
In order to understand the physiological
consequences of stopping steroid use here is a brief
review of the Hypothalamic-Pituitary-Testicular Axis
(HPTA)
hypothalamus 
GnRH

anterior pituitary  LH and FSH

testes

testosterone
Cessation of Steroid Use (cont’d)
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

inhibition
testosterone
inhibition
estrogen
Androgen use