Lecture 25 - Growth-promoting agents for skeletal muscle Flashcards
Medical applications of anabolic agents is important for treatment of many diseases including…
MDs HIV-AIDS cancer cachexia ageing (sarcopenia) sepsis denervation plaster casting enhancing regeneration after muscle injury
What are the hormonal therapeutic agents?
GH, testosterone, DHEA, SARMs
What are the hormonal therapeutic agents?
IGF-1, IL-15, TGF-Beta
What are the other growth promoter agents?
beta2-agonists
What is an Ergongenic aid?
Allows the bosy to train/perform at a higher level
What is the effect of endogenous levels and exogenous administration of testosterone?
endogenous levels
- responsible for male phenotype
- promotes bone and muscle growth
exogenous administration
- stimulates muscle protein synthesis
There are also synthetic analogues of testosterone and their precursors: nandrolone, oxandrolone, stanozolol
androgenic -anabolic steroids are synthetic derivatives of ______ capable of exerting strong effects on the body that can benefit athletic performance
androgenic -anabolic steroids are synthetic derivatives of testosterone capable of exerting strong effects on the body that can benefit athletic performance
True or false
testosterone replacement has been used to counteract loss of lean body mass in hypogonadal men, in older men with normal or low serum testosterone and HIV-infected men with low serum testosterone
true
muscle growth achieved
What are the Direct mechanisms of action for androgenic -anabolic steroids ?
Androgen receptor
- located in skeletal muscle
- stimulated by testosterone and DHT
receptor stimulation causes: increase in protein synthesis and therefore increase in muscle mass
What are the indirect mechanisms of action for androgenic -anabolic steroids ?
modulate gene expression of autocrine and paracrine mediators via other receptors (IFG-1)
Alter secretion of other hormones that suppress skeletal muscle growth - cortisol
What are the potential benefits of androgenic -anabolic steroids use?
Muscle hypertrophy
- increased protein synthesis
Ca2+ deposition in bones
lipolysis - increased lean body mass
increased RBC production - greater oxygen carrying capacity
motivation
what are the levels of testosterone administration and endogenous levels?
endogenous levels - 7mg testosterone/day
medicinal 4-10 mg/day
females
medicinal 0.04-0.12 mg/day
some studies have demonstrated enhanced muscle strength following testosterone administration, but other have reported…
n effect of androgen therapy on muscle function despite increases in muscle size
although anabolic steroids have been used for the treatment of HIV-related wasting and other wasting conditions for many years, many questions remain unanswered
e.g what are appropriate and safe doses for long-term administration and what are the associated potential risks or side-effects
What are the potential medical consequences of testosterone abuse?
at 100-350+ mg/day
liver dysfunction
testicular atrophy
increased body hair
male pattern baldness
gynaecomastia
acne
reduced HDL cholesterol levels
The abuse of testosterone in sports undermines the…
potential theapeutic applications
Where is growth hormone released from endogenousl and what inhibits it?
the ant. pituitary
somatostatin inhibits GH release
What is the mechanism of action of GH and its effects?
GH binds two receptors resulting in dimerisation
- causes the release of somatomedins = IGF-1
Effects - lipolysis increase lean body mass - bone growth protein accretion
rhGH(synthetic) has the same effect
Is there clinical evidence for increased performance, bone strength and decreased body fat for GH in sport?
No
True or false
rhGH is indistinguishable from GH
true
banned by IOC, but undetectable
What are the side effects of GH excess?
gigantism (pre-puberty)
acromegaly (post-puberty)
organomegaly
hypertension (increase Na reabsorbtion)
Collagen deposition
what is the therapeutic potential of GH?
improves muscle structure
mscuel function
numerous side effects
limited therapeutic potential
true or False
GH has been used by athletes since the 1980s to improve performance despite being banned for many years and appearing on the WADA list of banned substances
True
the actions of GH that interest athletes are anabolic and lipolytic
some of the anabolic GH actions are mediated through the generation of IGF-1 and there is anecdotaed evidence that this too is being abused by athletes either alone or in combination with GH
What does IGF-1 do?
growth factor with structural homology to insulin
involved with normal growth and repair of muscle
mediates action of GH
mechanism of Action: Binding of IGF-1 to receptor - increases protein synthesis Decreases protein degradation increase Muscle mass
How is IGF treated wrt sport?
what are its potential therapeutic benefits?
expensive (10,000 for 50mg)
does incerase muscle mass, strength and oxidative capacity
hence banned by the IOC
What are the thrapeutic benefits for Beta-agonists for sarcopenia?
increase muscle mass, Fibre size, absolutele force-producing capacity
cause slow-to-fast muscle fibre transitions (which causes hypertrophy)
enhance muscle repair after damage
Beta-adrenoceptor agonists (beta agonsits) are used for what?
used traditioanlly as bronchodilators for treating asthma, some have powerful anabolic effects on muscle however (when taken in higher doses and systemically rather than inhalation)
what is the mechanism of action of Beta-agonists?
acts through Pi3K/AKT and PKA
Increased levels of adrenergic stimulants reduces the response, how?
Desensitisation = same adrenoreceptor number but decreased receptor function
downregulation = decrease in adrenoceptor number, but same receptor fucntion
Can we separate the beneficial effects on skeletal muscle from those (delerious effects) on the heart?
all of these can be factors to deal with the CV side effect
choice of beta-agonists (clenbuterol is old, there are newer versions)
dosage
duration of treatment
mode of adminsitration
what family of receptors are beta-adrenoreceptors a part of?
G-protein coupled receptors (GPCRs)
True or False
currently in development, a synthetic receptor and an activator neither of which activates or impairs endogenous signalling
true
RASSLs and DREADDs - still in early phases of development
limits signalling to the tissue/region of interest - a result that current beta-agonists cannot achiebe
