Lecture 25 - Growth-promoting agents for skeletal muscle Flashcards

1
Q

Medical applications of anabolic agents is important for treatment of many diseases including…

A
MDs
HIV-AIDS
cancer cachexia
ageing (sarcopenia)
sepsis
denervation
plaster casting 
enhancing regeneration after muscle injury
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2
Q

What are the hormonal therapeutic agents?

A

GH, testosterone, DHEA, SARMs

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3
Q

What are the hormonal therapeutic agents?

A

IGF-1, IL-15, TGF-Beta

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4
Q

What are the other growth promoter agents?

A

beta2-agonists

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5
Q

What is an Ergongenic aid?

A

Allows the bosy to train/perform at a higher level

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6
Q

What is the effect of endogenous levels and exogenous administration of testosterone?

A

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

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7
Q

androgenic -anabolic steroids are synthetic derivatives of ______ capable of exerting strong effects on the body that can benefit athletic performance

A

androgenic -anabolic steroids are synthetic derivatives of testosterone capable of exerting strong effects on the body that can benefit athletic performance

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8
Q

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

A

true

muscle growth achieved

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9
Q

What are the Direct mechanisms of action for androgenic -anabolic steroids ?

A

Androgen receptor

  • located in skeletal muscle
  • stimulated by testosterone and DHT

receptor stimulation causes: increase in protein synthesis and therefore increase in muscle mass

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10
Q

What are the indirect mechanisms of action for androgenic -anabolic steroids ?

A

modulate gene expression of autocrine and paracrine mediators via other receptors (IFG-1)

Alter secretion of other hormones that suppress skeletal muscle growth - cortisol

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11
Q

What are the potential benefits of androgenic -anabolic steroids use?

A

Muscle hypertrophy
- increased protein synthesis

Ca2+ deposition in bones

lipolysis - increased lean body mass

increased RBC production - greater oxygen carrying capacity

motivation

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12
Q

what are the levels of testosterone administration and endogenous levels?

A

endogenous levels - 7mg testosterone/day

medicinal 4-10 mg/day

females
medicinal 0.04-0.12 mg/day

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13
Q

some studies have demonstrated enhanced muscle strength following testosterone administration, but other have reported…

A

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

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14
Q

What are the potential medical consequences of testosterone abuse?

A

at 100-350+ mg/day

liver dysfunction
testicular atrophy
increased body hair

male pattern baldness

gynaecomastia

acne

reduced HDL cholesterol levels

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15
Q

The abuse of testosterone in sports undermines the…

A

potential theapeutic applications

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16
Q

Where is growth hormone released from endogenousl and what inhibits it?

A

the ant. pituitary

somatostatin inhibits GH release

17
Q

What is the mechanism of action of GH and its effects?

A

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

18
Q

Is there clinical evidence for increased performance, bone strength and decreased body fat for GH in sport?

19
Q

True or false

rhGH is indistinguishable from GH

A

true

banned by IOC, but undetectable

20
Q

What are the side effects of GH excess?

A

gigantism (pre-puberty)

acromegaly (post-puberty)

organomegaly

hypertension (increase Na reabsorbtion)

Collagen deposition

21
Q

what is the therapeutic potential of GH?

A

improves muscle structure

mscuel function

numerous side effects
limited therapeutic potential

22
Q

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

A

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

23
Q

What does IGF-1 do?

A

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
24
Q

How is IGF treated wrt sport?

what are its potential therapeutic benefits?

A

expensive (10,000 for 50mg)

does incerase muscle mass, strength and oxidative capacity

hence banned by the IOC

25
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
26
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)
27
what is the mechanism of action of Beta-agonists?
acts through Pi3K/AKT and PKA
28
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
29
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
30
what family of receptors are beta-adrenoreceptors a part of?
G-protein coupled receptors (GPCRs)
31
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