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Anabolic-androgenic steroids (AAS) and other hormones such as growth hormone (GH) and insulin-like growth factor-1 (IGF-1) have been shown to increase muscle mass in patients suffering from various diseases related to muscle atrophy. Despite known side-effects associated with supraphysiologic doses of such drugs, their anabolic effects have led to their widespread use and abuse by bodybuilders and athletes such as strength athletes seeking to improve performance and muscle mass. On the other hand, resistance training (RT) has also been shown to induce significant endogenous hormonal (testosterone (T), GH, IGF-1) elevations. Therefore, some bodybuilders employ RT protocols designed to elevate hormonal levels in order to maximize anabolic responses. In this article, we reviewed current RT protocol outcomes with and without performance enhancing drug usage. Acute RT-induced hormonal elevations seem not to be directly correlated with muscle growth. On the other hand, supplementation with AAS and other hormones might lead to supraphysiological muscle hypertrophy, especially when different compounds are combined.
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The role of hormones in muscle hypertrophy
Julius Fink, Brad Jon Schoenfeld & Koichi Nakazato
To cite this article: Julius Fink, Brad Jon Schoenfeld & Koichi Nakazato (2017): The
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The role of hormones in muscle hypertrophy
Julius Fink
, Brad Jon Schoenfeld
and Koichi Nakazato
Graduate School of Medicine, Department of Metabolism and Endocrinology, Juntendo University, Tokyo, Japan;
Department of Health Sciences,
Lehman College, Bronx, NY, USA;
Graduate Schools of Health and Sport Science, Nippon Sport Science University, Tokyo, Japan
Anabolic-androgenic steroids (AAS) and other hormones such as growth hormone (GH) and insulin-like
growth factor-1 (IGF-1) have been shown to increase muscle mass in patients suffering from various
diseases related to muscle atrophy. Despite known side-effects associated with supraphysiologic doses
of such drugs, their anabolic effects have led to their widespread use and abuse by bodybuilders and
athletes such as strength athletes seeking to improve performance and muscle mass. On the other
hand, resistance training (RT) has also been shown to induce significant endogenous hormonal
(testosterone (T), GH, IGF-1) elevations. Therefore, some bodybuilders employ RT protocols designed
to elevate hormonal levels in order to maximize anabolic responses. In this article, we reviewed current
RT protocol outcomes with and without performance enhancing drug usage. Acute RT-induced hormo-
nal elevations seem not to be directly correlated with muscle growth. On the other hand, supplementa-
tion with AAS and other hormones might lead to supraphysiological muscle hypertrophy, especially
when different compounds are combined.
Received 20 July 2017
Accepted 15 November 2017
Resistance training;
endogenous hormonal
elevations; anabolic-
androgenic steroids
Although the anabolic effects of anabolicandrogenic steroids
(AAS) are widely recognized, there has been considerable
controversy about the hypertrophic effects of resistance train-
ing (RT)-induced endogenous hormonal elevations. Indeed,
while a recent study found a significant correlation between
RT-induced acute testosterone (T) elevations and long-term
muscle hypertrophy [1], several others failed to observe any
associations between these variables [24]. The theory sup-
porting the anabolic effects of RT-induced hormonal eleva-
tions is based on the concept of elevated post-exercise
anabolic hormones binding to hormone receptors and indu-
cing upregulation of several intracellular anabolic pathways
[1]. However, many studies only measured acute hormonal
changes and research about responses several days after train-
ing is lacking. The exact anabolic mechanism of RT-induced
hormonal elevations is not clear, but enhanced protein synth-
esis, decreased protein breakdown [5], satellite cell activation
[6], Wnt signaling [7], and SHBG receptor binding [8] are
speculated to be major factors. In addition, hormones might
act via non-genomic pathways to increase intracellular calcium
[9], thereby allowing for more force production [10] and ulti-
mately leading to improved training intensity and muscular
adaptations [1].
After the discovery and synthesis of T in the 1930s, AAS
were developed for the treatment of various diseases, growth
stimulation, and increase of muscle mass. By the 1970s, the
anabolic and performance-enhancing effects of AAS were dis-
covered by bodybuilders and some high-level athletes who
began to abuse them. Furthermore, the cosmetic effects of
increased muscle mass achieved with AAS led to the wide
spread of AAS abuse among bodybuilders. It has been
shown that supraphysiological levels of T increase muscle
mass not only in elderly and hypogonadal men but also in
healthy young men [1113]. Previous research on the admin-
istration of T derivatives (AAS) also showed improved body
composition after the treatment [1416]. Indeed, AAS are
synthetic substances derived from T with several different
anabolicandrogenic ratios, often used by athletes for pur-
poses such as bulking (increase of body mass in the off-
season) or cutting (reduction of body fat while maintaining
muscle mass pre-contest) cycles.
In addition to steroid hormones, naturally released peptide
and protein hormones (PH) such as growth hormone (GH) and
insulin-like growth factor 1 (IGF-1) have also been shown to
increase after RT [4,17]. GH became popular as performance-
enhancing drug in the early 1990s after the development of its
improved recombinant form [18]. The difficulty to detect GH
doping made this drug popular especially among body-
builders. However, even though some studies have found a
correlation between acute RT-induced GH increases and long-
term muscle hypertrophy [17], other studies failed to support
these findings [2,3]. It seems that GH improves body composi-
tion without direct effects on performance [19], making this
drug especially notorious among bodybuilders. Indeed, GH
increases serum IGF-1 concentrations [20] and might therefore
have anabolic effects besides its well-recognized lipolytic
CONTACT Julius Fink 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
© 2017 Informa UK Limited, trading as Taylor & Francis Group
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Since the anabolic effects of GH are mainly expressed via
the conversion to IGF-1, doping with IGF-1 has gained in
popularity; however, pharmaceutical grade IGF-1 has only
been recognized for human treatment recently and is not
widely available, giving rise to an increasing illicit production
and trade market. IGF-1 is sought for its anabolic properties
such as the ability to increase muscle fiber volume via activa-
tion of surrounding satellite cells [21].
Even though direct anabolic properties have not been
recognized, the use of insulin is also widespread among body-
builders and strength athletes seeking to increase muscle
mass [22]. Insulin has preventive properties with regard to
protein degradation [22] and insulin is a powerful transporter
hormone often used after or pre workout, despite the risk of
hypoglycemia, in order to transport as much nutrients as
possible to the damaged muscle cells. Insulin is also used by
some bodybuilders throughout the day in order to increase
nutrient uptake.
In view of the anabolic effects of AAS and PH on muscle
mass and performance, some bodybuilders and strength ath-
letes started to attempt to increase their natural levels of T,
GH, and IGF-1 via RT. However, the degree and duration of RT-
induced systemic hormonal increases might not lead to similar
effects as seen with exogenous administration of AAS or PH,
often used at doses leading to levels way above physiological
levels for long periods of time. The purpose of this review is to
elucidate the degree of RT-induced acute hormonal elevations
and if they can, to a certain degree, induce similar anabolic
pathways as compared to the exogenous administration of
AAS and PH.
Hypertrophic effects of RT-induced endogenous
hormonal elevations
The effects of RT on hormonal responses have been widely
investigated for several decades [2325]. Even though broad
guidelines exist regarding which type of RT protocols max-
imize the post-exercise hormonal response [26], the effects of
these acute RT-induced hormonal elevations on long-term
muscle hypertrophy are not currently clear.
Typical bodybuilding-type training protocols that include
large muscle groups with moderate intensity, high volume,
and relatively short rest periods are generally effective in
inducing acute T responses [26]. A positive correlation
(r= 0.76) between acute RT-induced T increases and muscle
cross-sectional area (CSA) has been previously observed [1,27].
However, acute elevations of T after RT last only for about
60 min and the average peak generally does not exceed
650 ng/dL [28], whereas an average dose of testosterone
replacement therapy (TRT) (200 mg of bi-weekly T-enanthate
supplementation), which would be considered a very low dose
among AAS abusers, leads to a sustained average of 815 ng/dL
[29]. Indeed, healthy males produce between 2.1 and 11.0 mg
of T per day [30]. TRT generally consists of a weekly adminis-
tration of 75100 mg of T or 150200 mg every 2 weeks [31]
to restore T within mid-normal physiological ranges (400
700 ng/dL) [32]. As a survey in the bodybuilding community
showed, more than 50% of AAS users use more than 1000 mg
of AAS weekly [33], which is 10 times more than natural T
synthesis or TRT doses, and leads to chronic serum T levels
several times higher than acute endogenous RT-induced T
elevations. From these numbers, we can extrapolate that
minor T raises occurring in response to RT cannot mimic the
effects of large amounts of exogenous AAS administration.
Besides, the various anabolic effects of AAS are much more
pronounced as compared to endogenous T due to the numer-
ous chemical structures of different AAS.
Endogenous GH release seems also to respond to smaller
muscle groups with low to medium intensity and short rest
periods [3], peaking between the period immediately after and
15 min after RT, coming back to baseline values around 60 min
post-RT [3,23,34]. Depending on the muscle group trained, RT-
induced GH responses can reach around 24 ug/L for large
muscle mass (whole body) [23] and around 12 ug/L for small
muscle mass (biceps and triceps) [3]. Studies supporting an
association between acute hormonal responses and long-term
muscle hypertrophy have either found a strong positive cor-
relation between GH and muscle fiber type I (r= 0.74) and II
(r= 0.71) [17] or a weak positive correlation (fiber type I
(r= 0.36) and II (r= 0.28)) [17,35]. Normal GH levels in healthy
males are <5 ug/L and GH-deficient adults are generally pre-
scribed around 0.250.5 U/kg weekly in order to restore
healthy GH levels [36], that is, between 25 and 50 U weekly
for a 100 kg individual. However, many bodybuilders seem to
add 2 to more than 15 U daily on top of their natural produc-
tion spread over the day divided in several injections in order
to constantly maintain elevated GH levels. Similar to T, acute
RT-induced elevations in GH may not be large and long
enough to induce similar effects to exogenous recombinant
GH administration.
Several studies have found the correlation between RT-
induced endogenous hormonal increases and muscle hyper-
trophy as trivial to weak [2,3,34,37]. Differences in measure-
ment methods and statistical analyses might contribute to the
discrepancies observed among studies. Indeed, studies report-
ing a correlation between GH and muscle hypertrophy have
measured muscle fiber CSA [17,35] and not total muscle CSA.
On the other hand, one study reporting anabolic effects of
acute T increases measured the correlation between differ-
ences in T responses before and after a 21-week training
period and changes in muscle CSA [27]. The other study
supporting a correlation between RT-induced acute T eleva-
tions and muscle hypertrophy used partial least squares
regression structural equation modeling in order to analyze
the relationships between endogenous responses to RT and
muscle hypertrophy [1]. From the results above and the large
body of evidence showing a lack of correlation between RT-
induced endocrine responses and muscle hypertrophy, it
appears that even if an association between RT-induced
acute hormonal elevations and long-term muscle hypertrophy
exists, the correlation might be so weak that it is undetectable
depending on the study design.
Attempts have been made to determine causality between
acute hormonal fluctuations and hypertrophy by carrying out
longitudinal research on the topic. West et al. employed a
within-subject design whereby 12 untrained young men
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performed unilateral arm curl exercise under two different
hormonal environments on separate days for 15 weeks [34].
One condition involved performance of 34 sets of elbow
flexion alone, thereby minimizing the post-exercise hormonal
response while the other condition involved the contralateral
arm carrying out the same elbow flexion protocol, which was
then followed immediately by performance of 5 sets of 10
repetitions of leg press and 3 sets of 12 repetitions of leg
extension/leg curl supersets to induce a high post-exercise
hormonal response. Results showed similar increases in mus-
cle girth between conditions, indicating that the acute sys-
temic response does not impact muscle growth. Subsequently,
Ronnestad et al. employed a similar design to that of West
et al., the primary difference being that the lower body exer-
cise was carried out prior to elbow flexion in the high hor-
mone condition [38]. Contrary to the findings of West et al.,
muscle CSAs of the elbow flexors were greater in the high
hormone condition in the middle aspect of the muscle, sug-
gesting a beneficial hypertrophic effect of acute systemic
elevations. As we can see from the studies above, it is difficult
to make comparisons between studies due to the differences
in study design and measurement methods, especially for
highly fluctuating data such as endocrine hormones (Table 1).
Hypertrophic effects of hormonal elevations induced
via exogenous administration of AAS
Initially developed for medical purposes, AAS have spread to
strength athletes and bodybuilders seeking supraphysiological
strength, endurance and muscle mass while taking serious
risks due to severe side effects [40]. A survey of 500 AAS
users showed that more than 75% of respondents were non-
competitive bodybuilders and non-athletes [33]. Furthermore,
more than half of the respondents acknowledged the use of
more than 1000 mg of T or similar AAS weekly, 25% reported
the use of GH and insulin, and more than 99% admitted
suffering from side effects related to AAS [33].
The administration of supraphysiological doses of T
(600 mg/week) has been shown to improve muscle mass
and strength with or without concomitant RT in healthy men
compared to individuals without T supplementation [41], leav-
ing no doubt of the anabolic effects of supraphysiological
levels of T. Studies on other AAS such as trenbolone, stanozo-
lol, or nandrolone have also shown improved body composi-
tion and/or performance in human or rodent studies [4244].
Even though many AAS have been developed, only a few are
for human consumption. Steroids like trenbolone are used as
growth promoters in cattle [45]. Several animal studies
[42,46,47] showed the potency of this compound making it
notorious among bodybuilders seeking trenbolone even
though it is not approved for human use. Moreover, the
combined use of AAS and PH has shown the possibility of
even larger improvements in fat-free mass as compared to the
single use of either compound [48], indicating synergistic
effects of AAS and PH. Especially the combination of GH
with insulin and AAS is believed to induce muscle mass
gains going far beyond the use of AAS only. Indeed, muscle
gene IGF-1 expression tends to increase with the combination
of T and GH [48] while insulin reduces proteolysis [49].
Many AAS share the following effects on performance and
muscle mass:
Increase in satellite cell and myonuclear number leading
to larger mitochondrial areas and lower nuclear-to-cyto-
plasmic ratio [6] which might lead to increased maximal
aerobic capacity (VO
Increased protein synthesis [30]
Decreased protein breakdown [30]
Nitrogen retention [30]
Increase in red blood cells and the following increase of
oxygen delivery to the muscles [51,52]
After the discovery of T in the 1930s, researchers tried to
find new chemical structures minimizing side effects and
maximizing anabolic effects. In many cases this means
increasing anabolic while decreasing androgenic effects.
In order to classify the muscle-building potency of AAS,
an anabolic to androgenic ratio chart is often used by
athletes. However, this ratio is based on the growth rate
of the levator ani muscle versus the prostate in rodents
after treatment with several AAS [53]. Nevertheless, even
though this ratio based on a specific muscle of rodents can
hardly be replicated to humans, it seems that many AAS
abusers still consider it when choosing their performance-
enhancing compound.
The major AAS used by athletes can be divided into three
groups [30]:
(1) Testosterone derivatives (T, Methyltestosterone,
Chlorodehydromethyltestosterone, Fluoxymesterone,
Boldenone): The compounds in this group are known
to induce fast strength and muscle gains but show a
high rate of aromatization. Due to the high water reten-
tion caused by aromatization, they are mainly used in
bulking cycles for quick mass gains.
(2) Dihydrotestosterone derivatives (Stanozolol,
Oxandrolone, Oxymetholone, Mesterolone,
Methenolone, Drostanolone): Even though most of
these compounds are highly androgenic, they have a
high binding affinity to the androgen receptor and are
potent strength and muscle mass builders. Due to the
DHT structure, these compounds cannot aromatize to
estrogen. Therefore, these compounds are often used
for cutting cycles and pre-contest.
(3) Nandrolone derivatives (Nandrolone, Trenbolone):
Compounds in this group show the highest anabolic
to androgenic ratio and have strong muscle building
effects. However, administration of nandrolone deriva-
tives can result in elevated progestogenic activity. The
use of this group of AAS is versatile and is used for both
bulking and cutting cycles.
Cellular memory can lengthen the effects of AAS even after
discontinuation of use. Indeed, a rodent study showed that
the increase in myonuclei is largely increased by AAS and
persists for several months after discontinuation [54].
Furthermore, these AAS-treated rodentsmuscle fiber CSA
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grew more than 30% within 6 days in response to overload
after 3 months of discontinuation of AAS treatment [54].
New discoveries in this field do not remain unnoticed by
AAS abusers seeking supraphysiological enhancement.
Indeed, combinations of several performance-enhancing com-
pounds might lead to synergistic effects. The main anabolic
effects of GH are believed to be indirect via conversion of GH
to IGF-1 in the liver triggering the IGF-1-Akt-mTOR pathway
[5557]. However, GH administration might induce insulin
resistance believed to be the main cause for cardiovascular
risks of increased GH levels [5862]. The administration of
insulin might restore normal skeletal muscle glucose transport
[63] and revert the effects of elevated GH. Therefore, many
AAS abusers using GH are thought to combine insulin in order
to avoid the negative side effects on insulin sensitivity induced
by GH. Further, besides its anabolic effects, T administration
also has been shown to improve insulin resistance [64,65].
Moreover, since both insulin and IGF-1 receptors are members
of the superfamily of receptor tyrosine kinase (RTKs) [66], some
athletes using GH seem to add insulin in order to increase
serum IGF-1 levels by preventing large amounts of IGF-1
binding to the insulin receptors [67].
In conclusion, acute RT-induced hormonal elevations may
have at best minor effects on muscle hypertrophy. Acute
hormonal responses might give us an indication on the inten-
sity and the following mechanical and metabolic stress of a
given RT protocol but should not be used as causative evi-
dence for a hypertrophic response to exercise.
On the other hand, high doses of AAS and PH have pro-
found effects on body composition by sustaining supraphy-
siological levels of anabolic hormones increasing protein
synthesis, satellite cell, and Wnt pathway activation while pre-
venting protein breakdown. The combination of AAS with GH,
IGF-1, and insulin might lead to supraphysiological levels of
muscle fiber growth (hypertrophy) and increase hyperplasia.
However, high doses of AAS and PH might cause severe side
effects. The fact that many of these compounds are only
available with prescription or are not even produced by phar-
maceutical companies nourishes illegal black markets where
products of questionable quality are sold to unaware athletes
seeking supraphysiological muscle gains. Furthermore, studies
of direct effects of AAS and PH combined with RT on muscle
Table 1. Previous research about the correlation between resistance training (RT)-induced hormonal increases and muscle hypertrophy.
Study Sample size and population Acute changes in hormones
Correlation between endogenous hormonal
increases and muscle size
Ahtiainen et al. [25]n=16
Age = 26.8 ± 3.5 yr
Recreational RT experience
FT, GH, T increased during RT Correlation between the difference in acute T
responses pre and post a 21-week training period
and changes in muscle CSA
Fink et al. [3]n=14
Age = 20.2 ± 0.3 yr
Athletes not involved in RT for
at least 2 years
increased immediately after RT and stayed
elevated for 30 min post-RT
IGF-1 increased immediately after RT
T did not significantly increase
No correlation between hormonal increases and
Fink et al. [4]n=20
Age = 19.9 ± 1.0 and
19.6 ± 1.0 yr
Athletes with experience in RT
GH increased immediately after RT No correlation between hormonal increases and
McCall et al. [17]n=11
Age = 1825 yr
Recreational RT
GH and IGF-1 increased mid- and post-RT
T did not significantly increase
No correlation between GH and CSA but a
correlation between GH and type I and II muscle
Mitchell et al. [39]n=23
Age = 24 ± 3 yr
Men recreationally active but
without RT for at least 1 year
N/A No correlation between FT, GH or IGF-1 and muscle
fiber hypertrophy
Mangine et al. [1]n=33
Men with at least 2 years of RT
N/A Correlation between T and muscle size
Morton et al. [2]n=49
Age = 23 ± 1 yr
RT for at least the past 2 years
N/A No correlation between acute anabolic hormonal
elevations and long-term muscle fiber
Rønnestad et al. [38]n=11
Age = 2034 yr
Untrained men
GH and T increased in the leg + arm RT
No changes in arm only RT
Greater CSA increases in a high hormone condition
as compared to low hormone condition
West et al. [37]n=8
Age = 20.0 ± 1.1 yr
Recreationally active men with
no RT activity over the past
GH IGF-1 and T increased immediately after RT
and stayed elevated for 30 min post-RT in the
arm + leg RT protocol
No changes in arm only RT
No improvement in anabolic signaling or acute
post-exercise muscle protein synthesis response
in a high hormone condition
West et al. [34]n=12
Age = 21.8 ± 0.4 yr
Recreationally active men with
no RT experience
GH, T, free T, and IGF-1 increased immediately
after RT and peaked at 15 min post-RT in the
arm + leg RT protocol
No changes in arm only RT
No improvements in total CSA or muscle fiber size
in a high hormone condition
West and Phillips [35]n=56
Young men recreationally active
with no RT activity over the
past 8 months
N/A Weak correlation between C and fiber area and
between GH and fiber area
C: Cortisol; CSA: cross-sectional area, FT, free testosterone, gh growth hormone, I: insulin, IGF-1: insulin-like growth factor 1, T: Testosterone.
Downloaded by [Gothenburg University Library] at 07:32 25 November 2017
mass and performance are lacking. This lack of knowledge
might be one reason for the ongoing abuse of illicit drugs
among bodybuilders and strength athletes. This field needs
more research in order to prevent AAS and PH abuse among
individuals endangering themselves by using drugs with
effects they are not aware of.
This paper is not funded.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial conflict with
the subject matter or materials discussed in the manuscript. This includes
employment, consultancies, honoraria, stock ownership or options, expert
testimony, grants or patents received or pending, or royalties.
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... IGF-1 has two different isoforms, IGF-1Ea and IGF-1Eb. The differing roles of these isoforms remain unclear; however, IGF-1Ea appears to be the main isoform involved in satellite cell activation and growth, and its expression is tightly correlated with muscle hypertrophy; thus, it is fundamental for muscle mass maintenance during aging and in ani-mals affected by muscular diseases [24][25][26]. IGF-1 controls protein synthesis by interacting with its receptor, IGF-1R, a receptor tyrosine kinase, to activate an intracellular signaling cascade that leads to the phosphorylation and activation of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. In this signaling cascade, AKT can phosphorylate and activate mTOR, thereby promoting protein synthesis [27]. ...
... IGF-1 has two different isoforms, IGF-1Ea and IGF-1Eb. The differing roles of these isoforms remain unclear; however, IGF-1Ea appears to be the main isoform involved in satellite cell activation and growth, and its expression is tightly correlated with muscle hypertrophy; thus, it is fundamental for muscle mass maintenance during aging and in animals affected by muscular diseases [24][25][26]. IGF-1 controls protein synthesis by interacting with its receptor, IGF-1R, a receptor tyrosine kinase, to activate an intracellular signaling cascade that leads to the phosphorylation and activation of the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. In this signaling cascade, AKT can phosphorylate and activate mTOR, thereby promoting protein synthesis [27]. ...
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Aging results in a progressive decline in skeletal muscle mass, strength and function, a condition known as sarcopenia. This pathological condition is due to multifactorial processes including physical inactivity, inflammation, oxidative stress, hormonal changes, and nutritional intake. Physical therapy remains the standard approach to treat sarcopenia, although some interventions based on dietary supplementation are in clinical development. In this context, thanks to its known anti-inflammatory and antioxidative properties, there is great interest in using extra virgin olive oil (EVOO) supplementation to promote muscle mass and health in sarcopenic patients. To date, the molecular mechanisms responsible for the pathological changes associated with sarcopenia remain undefined; however, a complete understanding of the signaling pathways that regulate skeletal muscle protein synthesis and their behavior during sarcopenia appears vital for defining how EVOO might attenuate muscle wasting during aging. This review highlights the main molecular players that control skeletal muscle mass, with particular regard to sarcopenia, and discusses, based on the more recent findings, the potential of EVOO in delaying/preventing loss of muscle mass and function, with the aim of stimulating further research to assess dietary supplementation with EVOO as an approach to prevent or delay sarcopenia in aging individuals.
... Furthermore, this is associated with a decrease in physical function and is itself strongly associated with morbidity and mortality (1). Skeletal muscle is a dynamic tissue with excellent regenerative ability and remarkable plasticity to adapt to various external stimuli such as external stimulation, intrinsic factors, or physical activity (2). Insulin-like growth factor-1 (IGF-1) plays a key role as a growth factor that regulates both muscle protein synthesis and degradation via multiple mechanisms such as ubiquitin-proteasome system, phosphatidylinositol 3 kinase/Protein kinase B/mammalian target of rapamycin and phosphatidylinositol 3 kinase/Protein kinase B/glycogen synthase kinase β pathways, and autophagy. ...
... Insulin-like growth factor-1 (IGF-1) plays a key role as a growth factor that regulates both muscle protein synthesis and degradation via multiple mechanisms such as ubiquitin-proteasome system, phosphatidylinositol 3 kinase/Protein kinase B/mammalian target of rapamycin and phosphatidylinositol 3 kinase/Protein kinase B/glycogen synthase kinase β pathways, and autophagy. IGF-1 also activates muscle stem (satellite) cell proliferation in muscle regeneration (2,3). It is known that growth hormone release and IGF-1 expression are stimulated directly or indirectly by γ-aminobutyric acid (GABA) (4,5). ...
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Introduction Oysters possess an excellent nutritional profile containing γ-aminobutyric acid (GABA). Previous data suggest that GABA is a potent bioactive compound for improving muscle health. Lactic acid fermentation is thought to increase GABA content. However, the effect of oral supplementation of fermented oyster extracts (FO) on human muscle strength and mass is unclear. Therefore, we tested the effects and safety of consumption of FO combined with regular walking for 12 weeks on muscle strength and mass in older adults with relatively low muscle mass. Materials and methods A randomized controlled trial was conducted on 54 adults between 50 and 78 years of age. Participants were randomized to receive either placebo or 1,200 mg FO daily for 12 weeks. By fermentation with Lactobacillus brevis BJ20, FO was prepared from Crassostrea gigas . At baseline and at 12 weeks after treatment, the following parameters of the participants were examined: knee strengths, handgrip strengths, body composition, blood tests, and 24-h dietary recall. All participants were required to walk for 30–60 min/day for >3 days/week during the trial period. Physical activity was assessed using an exercise log during the study. Results Of the 54 participants, 49 completed the trial without reporting adverse effects. FO supplementation over 12 weeks did not cause any increase in knee or grip strength compared to the control group. Also, no differences were observed in the muscle mass, growth hormone, muscle biomarkers, anti-inflammatory markers, and antioxidative markers between the two groups. None of the participants experienced adverse events. Application of FO was well tolerated, and no notable adverse effect was reported in both groups. Discussion FO supplementation with regular walking did not improve remarkably muscle function compared to regular walking alone in adults with relatively low muscle mass. Clinical Trial Registration [ ], identifier [NCT04109911].
... Deca Durabolin, testosterone, and Dianabol are some types of AAS that are wrongly used by athletes [2]. The use of AAS is well known and widespread worldwide because of its androgenic and anabolic properties that can increase muscle mass and strength to support athlete performance [3,4]. In addition, AAS is also able to reduce pain after high-intensity exercise by suppressing pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-a) and interleukin in the blood [5,6]. ...
... Naturally, testosterone is already produced by the male reproductive organs [69,70]. This hormone plays an important role in the physical development and sexual development of men [71][72][73][74][75][76].AAS has a similar role to the hormone testosterone, so athletes abuse AAS to increase muscle mass and muscle strength [3,4,22,27,77,78]. The use of AAS will cause negative feedback on the hypothalamic axis to the pituitary gland, altering the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), thereby causing infertility [79]. ...
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Anabolic-androgenic steroids (AAS) are large groups of molecules structurally and functionally similar to the male hormone testosterone. The use of AAS is well known and widespread worldwide due to its androgenic and anabolic properties that can increase muscle mass and strength to support athlete performance. The prevalence of AAS worldwide reaches an incidence of 5% and is generally used by men aged 18-35. AAS has many side effects on the body's organs and is a serious problem for public health and athletics. This review aims to highlight the abuse of AAS and its detrimental effects on the health of human organs. Oxidative stress and apoptosis are common mechanisms that cause organ damage due to AAS use. Chronic administration of high doses of AAS results in cardiac dysfunction and increases the risks of life-threatening arrhythmias and sudden death. In addition, several organs that have the potential to be damaged by the use of AAS include the liver, kidneys, brain, musculoskeletal system, and reproductive organs. In this regard, education intervention and knowledge sharing are the important factors that should be used to raise awareness about preventing AAS abuse.
... The experimental data showed that there was no significant difference in T and C in the three supplement strategies at different time points. As the most active androgen in the body, testosterone can stimulate tissues to take up amino acids and promote protein synthesis [45,46]. Overall, testosterone can promote anabolic metabolism in the body. ...
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Background: The purpose of this study is to explore the effect of carbohydrate only or carbohydrate plus protein supplementation on endurance capacity and muscle damage. Methods: Ten recreationally active male runners (VO2max: 53.61 ± 3.86 ml/kg·min) completed run-to-exhaustion test three times with different intakes of intervention drinks. There was a 7-day wash-out period between tests. Each test started with 60 minutes of running at 70% VO2max (phase 1), followed by an endurance capacity test: time-to-exhaustion running at 80% VO2max (phase 2). Participants randomly ingested either 1) 0.4 g/kg BM carbohydrate before phase 1 and before phase 2 (CHO+CHO), 2) 0.4 g/kg BM protein before phase 1 and 0.4 g/kg BM carbohydrate before phase 2 (PRO+CHO), or 3) 0.4 g/kg BM carbohydrate before phase 1 and 0.4 g/kg BM protein before phase 2 (CHO+PRO). All subjects ingested carbohydrate (CHO) 1.2 g/kg BM during phase 1, and blood samples were obtained before, immediately, and 24 h after exercise for measurements of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), and myoglobin (MB). Results: There was no significant difference in time to exhaustion between the three supplement strategies (CHO+CHO: 432 ± 225 s; PRO+CHO: 463 ± 227 s; CHO+PRO: 461 ± 248 s). However, ALT and AST were significantly lower in PRO+CHO than in CHO+CHO 24 h after exercise (ALT: 16.80 ± 6.31 vs. 24.39 ± 2.54 U/L; AST: 24.06 ± 4.77 vs. 31.51 ± 7.53 U/L, p < 0.05). MB was significantly lower in PRO+CHO and CHO+PRO than in CHO+CHO 24 h after exercise (40.7 ± 15.2; 38.1 ± 14.3; 64.3 ± 28.9 ng/mL, respectively, p < 0.05). CK increased less in PRO+CHO compared to CHO+CHO 24 h after exercise (404.22 ± 75.31 VS. 642.33 ± 68.57 U/L, p < 0.05). Conclusion: Carbohydrate and protein supplement strategies can reduce muscle damage caused by endurance exercise, but they do not improve endurance exercise capacity.
... For striated muscle hypertrophy, several pathways imply specific triggers, ligands or receptors before the induction of different cascades of events. The trigger signals may be soluble molecules coming from endocrine secretions, such as adrenaline/PKA [39], insulin/PI3K [40] and thyroid hormones/nuclear thyroid receptors [41] or cytokines, such as cardiotrophin/SHP2 [42], LIF/Ras [43], and TGF/TAK1 [44]. Other signals involve amino acids, such as leucine/mTOR [45], microRNAs [46] or nitrogen oxide [47]. ...
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The induction of protein synthesis is crucial to counteract the deconditioning of neuromuscular system and its atrophy. In the past, hormones and cytokines acting as growth factors involved in the intracellular events of these processes have been identified, while the implications of signaling pathways associated with the anabolism/catabolism ratio in reference to the molecular mechanism of skeletal muscle hypertrophy have been recently identified. Among them, the mechanotransduction resulting from a mechanical stress applied to the cell appears increasingly interesting as a potential pathway for therapeutic intervention. At present, there is an open question regarding the type of stress to apply in order to induce anabolic events or the type of mechanical strain with respect to the possible mechanosensing and mechanotransduction processes involved in muscle cells protein synthesis. This review is focused on the muscle LIM protein (MLP), a structural and mechanosensing protein with a LIM domain, which is expressed in the sarcomere and costamere of striated muscle cells. It acts as a transcriptional cofactor during cell proliferation after its nuclear translocation during the anabolic process of differentiation and rebuilding. Moreover, we discuss the possible opportunity of stimulating this mechanotransduction process to counteract the muscle atrophy induced by anabolic versus catabolic disorders coming from the environment, aging or myopathies. Keywords: mechanotransduction; striated muscle; ultrasound stimulation; prophylaxis; atrophy; MLP
Background: Skeletal muscle atrophy is a common condition without a pharmacologic therapy. AGGF1 encodes an angiogenic factor that regulates cell differentiation, proliferation, migration, apoptosis, autophagy and endoplasmic reticulum stress, promotes vasculogenesis and angiogenesis and successfully treats cardiovascular diseases. Here, we report the important role of AGGF1 in the pathogenesis of skeletal muscle atrophy and attenuation of muscle atrophy by AGGF1. Methods: In vivo studies were carried out in impaired leg muscles from patients with lumbar disc herniation, two mouse models for skeletal muscle atrophy (denervation and cancer cachexia) and heterozygous Aggf1+/- mice. Mouse muscle atrophy phenotypes were characterized by body weight and myotube cross-sectional areas (CSA) using H&E staining and immunostaining for dystrophin. Molecular mechanistic studies include co-immunoprecipitation (Co-IP), western blotting, quantitative real-time PCR analysis and immunostaining analysis. Results: Heterozygous Aggf1+/- mice showed exacerbated phenotypes of reduced muscle mass, myotube CSA, MyHC (myosin heavy chain) and α-actin, increased inflammation (macrophage infiltration), apoptosis and fibrosis after denervation and cachexia. Intramuscular and intraperitoneal injection of recombinant AGGF1 protein attenuates atrophy phenotypes in mice with denervation (gastrocnemius weight 81.3 ± 5.7 mg vs. 67.3 ± 5.1 mg for AGGF1 vs. buffer; P < 0.05) and cachexia (133.7 ± 4.7 vs. 124.3 ± 3.2; P < 0.05). AGGF1 expression undergoes remodelling and is up-regulated in gastrocnemius and soleus muscles from atrophy mice and impaired leg muscles from patients with lumbar disc herniation by 50-60% (P < 0.01). Mechanistically, AGGF1 interacts with TWEAK (tumour necrosis factor-like weak inducer of apoptosis), which reduces interaction between TWEAK and its receptor Fn14 (fibroblast growth factor-inducing protein 14). This leads to inhibition of Fn14-induced NF-kappa B (NF-κB) p65 phosphorylation, which reduces expression of muscle-specific E3 ubiquitin ligase MuRF1 (muscle RING finger 1), resulting in increased MyHC and α-actin and partial reversal of atrophy phenotypes. Autophagy is reduced in Aggf1+/- mice due to inhibition of JNK (c-Jun N-terminal kinase) activation in denervated and cachectic muscles, and AGGF1 treatment enhances autophagy in two atrophy models by activating JNK. In impaired leg muscles of patients with lumbar disc herniation, MuRF1 is up-regulated and MyHC and α-actin are down-regulated; these effects are reversed by AGGF1 by 50% (P < 0.01). Conclusions: These results indicate that AGGF1 is a novel regulator for the pathogenesis of skeletal muscle atrophy and attenuates skeletal muscle atrophy by promoting autophagy and inhibiting MuRF1 expression through a molecular signalling pathway of AGGF1-TWEAK/Fn14-NF-κB. More importantly, the results indicate that AGGF1 protein therapy may be a novel approach to treat patients with skeletal muscle atrophy.
Heat stress significantly impairs the growth performance of broilers, which causes serious losses to the poultry industry every year. Thus, understanding the performance of indigenous chicken breeds under such environment is crucial to address heat stress problem. The purpose of this study was to investigate the effects of heat stress (HS) on production performance, tissue histology, heat shock response (HSP70, HSP90), and muscle growth-related genes (GHR, IGF-1, and IGF-1R) of Normal yellow chicken (NYC) and Dwarf yellow chicken (DYC). Seventy-two female birds from each strain were raised under normal environmental conditions up to 84 days, with birds from each strain being divided into two groups (HS and control). In the HS group, birds were subjected to high temperature at 35 ± 1 °C for 8 h daily and lasted for a week, while in the control group, birds were raised at 28 ± 1 °C. At 91 days old, bird's liver, hypothalamus, and breast muscle tissues were collected to evaluate the gene expression, histological changes, and the production performance. The Feed intake, weight gain ratio, total protein intake and protein efficiency ratio showed a significant reduction in the treatments (P
Cancer cachexia is a disorder characterized by involuntary weight loss and impaired physical performance. Decline in physical performance of patients with cachexia is associated with poor quality of life, and currently there are no effective pharmacological interventions that restore physical performance. Here we examine the effect of GDF15 neutralization in a mouse model of cancer-induced cachexia (TOV21G) that manifests weight loss and muscle function impairments. With comprehensive assessments, our results demonstrate that cachectic mice treated with the anti-GDF15 antibody mAB2 exhibit body weight gain with near-complete restoration of muscle mass and markedly improved muscle function and physical performance. Mechanistically, the improvements induced by GDF15 neutralization are primarily attributed to increased caloric intake, while altered gene expression in cachectic muscles is restored in caloric-intake-dependent and -independent manners. The findings indicate potential of GDF15 neutralization as an effective therapy to enhance physical performance of patients with cachexia.
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Physical activity has been known as an essential element to promote human health for centuries. Thus, exercise intervention is encouraged to battle against sedentary lifestyle. Recent rapid advances in molecular biotechnology have demonstrated that both endurance and resistance exercise training, two traditional types of exercise, trigger a series of physiological responses, unraveling the mechanisms of exercise regulating on the human body. Therefore, exercise has been expected as a candidate approach of alleviating a wide range of diseases, such as metabolic diseases, neurodegenerative disorders, tumors, and cardiovascular diseases. In particular, the capacity of exercise to promote tissue regeneration has attracted the attention of many researchers in recent decades. Since most adult human organs have a weak regenerative capacity, it is currently a key challenge in regenerative medicine to improve the efficiency of tissue regeneration. As research progresses, exercise-induced tissue regeneration seems to provide a novel approach for fighting against injury or senescence, establishing strong theoretical basis for more and more “exercise mimetics.” These drugs are acting as the pharmaceutical alternatives of those individuals who cannot experience the benefits of exercise. Here, we comprehensively provide a description of the benefits of exercise on tissue regeneration in diverse organs, mainly focusing on musculoskeletal system, cardiovascular system, and nervous system. We also discuss the underlying molecular mechanisms associated with the regenerative effects of exercise and emerging therapeutic exercise mimetics for regeneration, as well as the associated opportunities and challenges. We aim to describe an integrated perspective on the current advances of distinct physiological mechanisms associated with exercise-induced tissue regeneration on various organs and facilitate the development of drugs that mimics the benefits of exercise.
The purpose of this article is to provide the school nurse with the ability to recognize performance and appearance enhancing substance use and understand treatment and prevention strategies to reduce associated health risks. The use of appearance and performance enhancing drugs and substances, also known as "doping," has been an ethical and health issue in sports for many years. It is vital that school nurses learn to recognize performance and appearance enhancing substance use to ensure student athletes and exercisers receive the care and education they need. Commonly used performance and appearance enhancing substances include anabolic-androgenic steroids, stimulants, diuretics, growth hormone, and supplements. Signs and symptoms that may look similar to other health concerns include palpitations, stunted growth, acne, severe headaches, muscle cramps, dizziness, and dehydration, but some long-term severe complications occur as well. Doping can lead to severe and sometimes permanent organ damage, including liver, kidney, and heart disease. The school nurse can play a key role by working with parents, coaches, school counselors, and educators to foster an anti-doping culture.
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Partial least squares regression structural equation modeling (PLS-SEM) was used to examine relationships between the endocrine response to resistance exercise and muscle hypertrophy in resistance-trained men. Pre-testing (PRE) measures of muscle size (thickness and cross-sectional area) of the vastus lateralis and rectus femoris were collected in 26 resistance-trained men. Participants were randomly selected to complete a high-volume (VOL, n=13, 10–12RM, 1-min rest) or high-intensity (INT, n = 13, 3–5RM, 3-min rest) resistance training program. Blood samples were collected at baseline, immediately post-exercise, 30-min, and 60-min post-exercise during weeks 1 (WK1) and 8 (WK8) of training. The hormonal responses (testosterone, growth hormone [22 kD], insulin-like growth factor-1, cortisol, and insulin) to each training session were evaluated using area-under-the-curve (AUC) analyses. Relationships between muscle size (PRE), AUC values (WK1 + WK8) for each hormone, and muscle size (POST) were assessed using a consistent PLS-SEM algorithm and tested for statistical significance (p<0.05) using a 1000 samples consistent bootstrapping analysis. Group-wise comparisons for each relationship were assessed via independent t-tests. The model explained 73.4% (p<0.001) of variance in muscle size at POST. Significant pathways between testosterone and muscle size at PRE (p=0.043) and muscle size at POST (p=0.032) were observed. The ability to explain muscle size at POST improved when the model was analyzed by group (INT: VOL: p<0.001). No group differences in modal quality were found. Exercise-induced testosterone elevations, independent of the training programs used in this study, appear to be related to muscle growth.
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We reported, using a unilateral resistance training (RT) model, that training with high or low loads (mass per repetition) resulted in similar muscle hypertrophy and strength improvements in RT-naïve subjects. Here we aimed to determine whether the same was true in men with previous RT experience using a whole-body RT program and whether post-exercise systemic hormone concentrations were related to changes in hypertrophy and strength. Forty-nine resistance-trained men (mean ± SEM, 23 ± 1 y) performed 12 wk of whole-body RT. Subjects were randomly allocated into a higher-repetition (HR) group who lifted loads of ~30-50% of their maximal strength (1RM) for 20-25 repetitions/set (n=24) or a lower-repetition (LR) group (~75-90% 1RM, 8-12 repetitions/set, n=25), with all sets being performed to volitional failure. Skeletal muscle biopsies, strength testing, DXA scans, and acute changes in systemic hormone concentrations were examined pre- and post-training. In response to RT, 1RM strength increased for all exercises in both groups (p < 0.01), with only the change in bench press being significantly different between groups (HR: 9 ± 1 vs. LR: 14 ±1 kg, p = 0.012). Fat- and bone-free (lean) body mass, type I and type II muscle fibre cross sectional area increased following training (p < 0.01) with no significant differences between groups. No significant correlations between the acute post-exercise rise in any purported anabolic hormone and the change in strength or hypertrophy were found. In congruence with our previous work, acute post-exercise systemic hormonal rises are not related to or in any way indicative of RT-mediated gains in muscle mass or strength. Our data show that in resistance-trained individuals load, when exercises are performed to volitional failure, does not dictate hypertrophy or, for the most part, strength gains.
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Objective: One-third of men with type 2 diabetes have hypogonadotropic hypogonadism (HH). We conducted a randomized placebo controlled trial to evaluate the effect of testosterone replacement on insulin resistance in men with type 2 diabetes and HH. Research design and methods: A total of 94 men with type 2 diabetes were recruited into the study; 50 men were eugonadal, while 44 men had HH. Insulin sensitivity was calculated from the glucose infusion rate (GIR) during hyperinsulinemic-euglycemic clamp. Lean body mass and fat mass were measured by DEXA and MRI. Subcutaneous fat samples were taken to assess insulin signaling genes. Men with HH were randomized to receive intramuscular testosterone (250 mg) or placebo (1 mL saline) every 2 weeks for 24 weeks. Results: Men with HH had higher subcutaneous and visceral fat mass than eugonadal men. GIR was 36% lower in men with HH. GIR increased by 32% after 24 weeks of testosterone therapy but did not change after placebo (P = 0.03 for comparison). There was a decrease in subcutaneous fat mass (-3.3 kg) and increase in lean mass (3.4 kg) after testosterone treatment (P < 0.01) compared with placebo. Visceral and hepatic fat did not change. The expression of insulin signaling genes (IR-β, IRS-1, AKT-2, and GLUT4) in adipose tissue was significantly lower in men with HH and was upregulated after testosterone treatment. Testosterone treatment also caused a significant fall in circulating concentrations of free fatty acids, C-reactive protein, interleukin-1β, tumor necrosis factor-α, and leptin (P < 0.05 for all). Conclusions: Testosterone treatment in men with type 2 diabetes and HH increases insulin sensitivity, increases lean mass, and decreases subcutaneous fat.
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The homodimeric insulin and type 1 insulin-like growth factor receptors (IR and IGF-1R) share a common architecture and each can bind all three ligands within the family: insulin and insulin-like growth factors I and II (IGF-I and IFG-II). The receptor monomers also assemble as heterodimers, the primary ligand-binding sites of which each comprise the first leucine-rich repeat domain (L1) of one receptor type and an α-chain C-terminal segment (αCT) of the second receptor type. We present here crystal structures of IGF-I bound to such a hybrid primary binding site and of a ligand-free version of an IR αCT peptide bound to an IR L1 plus cysteine-rich domain construct (IR310.T). These structures, refined at 3.0-Å resolution, prove congruent to respective existing structures of insulin-complexed IR310.T and the intact apo-IR ectodomain. As such, they provide key missing links in the emerging, but sparse, repertoire of structures defining the receptor family. Copyright © 2015 Elsevier Ltd. All rights reserved.
Objective: Illicit use of growth hormone (GH) as a performance-enhancing drug among athletes is prevalent, although the evidence of such effects in healthy, young subjects is sparse. We therefore performed a meta-analysis of published studies on the effect of GH administration on body composition, substrate metabolism, and athletic performance in healthy, young subjects. Design: The English-language based databases PubMed, EMBASE, and Cochrane Central Register of Controlled Trials were searched, and eligible articles were reviewed in accordance with the PRISMA guidelines. Fifty-four potentially relevant articles were retrieved of which 11 were included in this analysis comprising 254 subjects. Results: Administration of GH significantly increased lean body mass (p<0.01) and decreased fat mass (p<0.01). In addition, GH increased the exercising levels of glycerol (p=0.01) and free fatty acids (p<0.01), but did not alter the respiratory quotient during exercise (p=0.30). GH significantly increased anaerobic exercise capacity (p<0.01) in the only study which investigated this, but did not over weeks to months improve muscle strength (p=0.36) or maximum oxygen uptake (p=0.89). Conclusion: GH administration elicits significant changes in body composition, but does not increase either muscle strength or aerobic exercise capacity in healthy, young subjects.
The goal of testosterone replacement therapy (TRT) is to return serum testosterone levels to within physiologic range and improve symptoms in hypogonadal men. Some of the symptoms aimed to improve upon include decreased libido, erectile dysfunction, infertility, hot flashes, depressed mood, and loss of muscle mass or hair. Clinical use of testosterone for replacement therapy began approximately 70 years ago. Over the decades, numerous preparations and formulations have been developed primarily focusing on different routes of delivery and thus pharmacokinetics (PKs). Currently the routes of delivery approved for use by the United States Food and Drug Administration encompasses buccal, nasal, subdermal, transdermal, and intramuscular (IM). Many factors must be considered when a clinician is choosing the most correct formulation for a patient. As this decision depends highly on the patient, active patient participation is important for effective selection. The aim of this review is to describe and compare all testosterone preparations currently available and approved by the United States Food and Drug Administration. Areas of focus will include pharmacology, PKs, adverse effects, and specifics related to individual delivery routes.
We investigated the effects of volume-matched resistance training (RT) with different training loads and rest intervals on acute responses and long-term muscle and strength gains. Ten subjects trained with short rest (30 s) combined with low load (20 RM) (SL) and ten subjects performed the same protocol with long rest (3 min) and high load (8 RM) (LH). Cross-sectional area (CSA) of the upper arm was measured by magnetic resonance imaging before and after 8 weeks of training. Acute stress markers such as growth hormone (GH) and muscle thickness (MT) changes have been assessed pre and post a single RT session. Only the SL group demonstrated significant increases in GH (7704·20 ± 11833·49%, P<0·05) and MT (35·2 ± 16·9%, P<0·05) immediately after training. After 8 weeks, the arm CSA s in both groups significantly increased [SL: 9·93 ± 4·86% (P<0·001), LH: 4·73 ± 3·01% (P<0·05)]. No significant correlation between acute GH elevations and CSA increases could be observed. We conclude that short rest combined with low-load training might induce a high amount of metabolic stress ultimately leading to improved muscle hypertrophy while long rest with high-load training might lead to superior strength increases. Acute GH increases seem not to be directly correlated with muscle hypertrophy.
We investigated the effects of low-load resistance training to failure performed with different rest intervals on acute hormonal responses and long-term muscle and strength gains. In the acute study, 14 participants were assigned to either a short rest (S, 30 s) or long rest (L, 150 s) protocol at 40% one-repetition maximum. Blood samples were taken before and after the workout. Both groups showed significant (p<0.05) increases in growth hormone and insulin-like growth factor 1 immediately post-workout. In the longitudinal study, the same protocol as in the acute study was performed 2 times per week for 8 weeks by 21 volunteers. Both groups showed significant increases in triceps (S: 9.8±8.8%, L: 10.6±9.6%, p<0.05) and thigh (S: 5.7±4.7%, L: 8.3±6.4%, p<0.05) cross-sectional area. One-repetition maximum also significantly increased for the bench press (S: 9.9±6.9%, L: 6.5±5.8%, p<0.05) and squat (S: 5.2±6.7%, L: 5.4±3.5%, p<0.05). In conclusion, our results suggest that acute hormonal responses, as well as chronic changes in muscle hypertrophy and strength in low-load training to failure are independent of the rest interval length.
The androgen-induced alterations in adult rodent skeletal muscle fibre cross-sectional area (fCSA), satellite cell content and myostatin (Mstn) were examined in 10-month-old Fisher 344 rats (n = 41) assigned to Sham surgery, orchiectomy (ORX), ORX + testosterone (TEST; 7.0 mg week(-1) ) or ORX + trenbolone (TREN; 1.0 mg week(-1) ). After 29 days, animals were euthanised and the levator ani/bulbocavernosus (LABC) muscle complex was harvested for analyses. LABC muscle fCSA was 102% and 94% higher in ORX + TEST and ORX + TREN compared to ORX (p < .001). ORX + TEST and ORX + TREN increased satellite cell numbers by 181% and 178% compared to ORX, respectively (p < .01), with no differences between conditions for myonuclear number per muscle fibre (p = .948). Mstn protein was increased 159% and 169% in the ORX + TEST and ORX + TREN compared to ORX (p < .01). pan-SMAD2/3 protein was ~30-50% greater in ORX compared to SHAM (p = .006), ORX + TEST (p = .037) and ORX + TREN (p = .043), although there were no between-treatment effects regarding phosphorylated SMAD2/3. Mstn, ActrIIb and Mighty mRNAs were lower in ORX, ORX + TEST and ORX + TREN compared to SHAM (p < .05). Testosterone and trenbolone administration increased muscle fCSA and satellite cell number without increasing myonuclei number, and increased Mstn protein levels. Several genes and signalling proteins related to myostatin signalling were differentially regulated by ORX or androgen therapy.
The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone deficiency (TD) and potentially impairs the therapeutic efficacy of classical testosterone replacement therapy (TRT). We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone in a model of TD with the metabolic syndrome (MetS). Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose diet (HF/HS). Following 8 weeks of feeding, rats underwent sham surgery or an orchiectomy (ORX). Alzet mini-osmotic pumps containing either vehicle, 2 mg/kg/day testosterone (TEST) or 2 mg/kg/day trenbolone (TREN) were implanted in HF/HS+ORX rats. Body composition, fat distribution, lipid profile and insulin sensitivity were assessed. Infarct size was quantified to assess myocardial damage following in vivo ischaemia-reperfusion, before cardiac and prostate histology was performed. The HF/HS+ORX animals had increased subcutaneous and visceral adiposity; circulating triglycerides, cholesterol and insulin; and myocardial damage, with low circulating testosterone compared to CTRLs. Both TEST and TREN protected HF/HS+ORX animals against subcutaneous fat accumulation, hypercholesterolaemia and myocardial damage. However, only TREN protected against visceral fat accumulation, hypertriglyceridaemia and hyperinsulinaemia; and reduced myocardial damage relative to CTRLs. TEST caused widespread cardiac fibrosis and prostate hyperplasia, which were less pronounced with TREN. We propose that TRT may have contraindications for males with TD and obesity-related MetS. TREN treatment may be more effective in restoring androgen status and reducing cardiovascular risk in males with TD and MetS.