Heavy Resistance Exercise Acutely Lowers Androgen Receptor Levels In Men
By Karl Hoffmann
Ratamess and coworkers recently published the results of a study that looked
at the hormonal profile and androgen receptor content in the vastus lateralis
muscle (a portion of the muscles comprising the quadriceps) of men following
two exercise protocols [1]. The results were a bit surprising in light of some
previous studies, and suggest a possible supplement regimen to offset some of
the negative effects that were observed. The salient results of their research
were (a) an increase in both cortisol and testosterone levels after multiple
sets of squats; and (b) a significant downregulation of the androgen receptor
in biopsied muscle tissue.
Several previous studies have examined hormonal changes in cortisol,
testosterone, and growth hormone (GH) during and following resistance exercise
[2-4]. In [2] Kraemer et.al. observed an increase in both testosterone and GH
after heavy resistance exercise. Hakkinen and Pakarinen observed increases in
free and total testosterone, cortisol, and GH after an acute bout of heavy squatting
[3]. Kraemer et.al. examined plasma hormone changes after an intense bout of
cycling and noted a significant increase in cortisol [4]. The current study
and the earlier ones cited show a trend of increased cortisol and testosterone
immediately after strenuous exercise.
The current study by Ratamass et.al. is the first to look at androgen receptor
content in worked muscle immediately post-exercise. While the elevated
testosterone that many studies show occurs after exercise sounds beneficial,
if receptor levels are low, then the increased testosterone would be of less
anabolic value than if receptor levels were unchanged or increased. In fact,
a
depressed level of AR is exactly what Ratamass and coworkers found. The
downregulation of AR coupled with high cortisol levels post-exercise would be
expected to make for a metabolic state characterized by net catabolism.
To quote from the current study under investigation,
"...acute hormonal elevations are without context unless subsequent interaction
with a specific membrane bound or nuclear receptor occurs and the appropriate
signal is transduced".
In other words, what good is the extra testosterone produced during lifting
if
the receptors aren't there to accept it?
In the current study, 9 young resistance trained men performed two exercise
protocols. One consisted of a single set (SS) of 10 reps of heavy squats. The
second exercise involved 6 sets of 10 reps of squats (MS). Weights were
determined for each individual by measuring their 1 Rep Max (RM) and then having
them squat at 80 - 85% of the (RM). The average RM was 330.4 lbs.
Plasma testosterone and cortisol were measured every 15 minutes for 1 hour
after both sessions. The vastus lateralis was biopsied to determine AR content
1 hour after training. The results, taken from [1] are shown below.
As can be seen, there was no significant change in cortisol in is SS group,
while cortisol rose about 40% in the MS group after 30 minutes
Similarly, testosterone did not change in the SS group but showed a transient
increase of 20% in the MS group.
The bar graph below from [1] shows relative vastus lateralis AR content at
baseline and 1 hour after completion of exercise. The drop in AR content in
the worked muscle is clear
The authors of the present study attribute the decline in androgen receptors
to an overall loss of protein due to the demands of strenuous exercise. Cortisol
is highly catabolic to proteins and does not discriminate between contractile
proteins and noncontractile proteins, such as the androgen receptor, which itself
is a protein. A number of studies have shown that the AR is upregulated after
a longer post exercise time period. For example, Bamman & Shipp reported
that in humans AR messenger RNA in the vastus lateralis increased 63% and 102%
respectively 48 hours following 8 sets of 8 reps of either eccentric (110% of
1 RM) or concentric ( 85% of 1RM) squats [5]. Thus resistance exercise may ultimately
upregulate the AR, but the initial response appears to be a catabolic one, based
on the current study.
One might be tempted to speculate the increased testosterone and decreased
AR may cancel each other out. This may not be the case. Another interesting
finding of this study was the individual baseline 1 RM was independent of plasma
testosterone levels, but correlated highly with androgen receptor content. So
an individual's AR levels may be more indicative of their strength that their
testosterone levels.
Certain anabolic steroids such as Anavar (oxandrolone), that are considered
to have a very high anabolic to androgenic ratio are noted for their ability
to
upregulate the AR [6].
Since it is generally believed that protein synthesis peaks in the few hours
after a training session, it makes sense to attempt to limit the downregulation
of the AR that seems to occur after exercise. One strategy might be to
supplement with amino acids, especially Branched Chain Amino Acids rich in
leucine. Besides being anabolic in and of itself, leucine taken as a supplement
will be preferentially oxidized for fuel, sparing body proteins, which would
likely include the AR:
The Ergogenic Effects of Citrulline Malate combined with Branched Chain Amino
Acids
Another strategy would be to combine a cortisol blocker such as 7-oxo DHEA
and/or phosphatidyl serine to the BCAA mix to help limit protein catabolism.
While I don't advocate the use of anabolic steroids, clearly agents such as
Anavar which upregulate the AR would likely prove helpful as well.
While elevated cortisol is a likely contributor to protein catabolism, other
proteolytic mechanisms may be at work as well. The body has three independent
systems for degrading and disposing of proteins. These are the so-called lysosomal
and calcium mediated proteases, and the ATP-ubiquitin dependent proteolytic
pathway. However, cortisol has been implicated in activting the ATP-ubiquitin
proteolytic pathway [7], which may ultimately be the mechanism by which cortisol
exerts its catabolic action; so here again cortisol blockers might help.
We mentioned Anavar above. Besides upregulating the AR, Anavar also antagonizes
the catabolic actions of cortisol [8]. Calcium mediated proteolysis is suppressed
by cyclic adenosine monophosphate (cAMP), and forskolin is well know to elevate
cAMP. Thus forskolin may be a worthwhile supplement to defend against this pathway
of protein breakdown. Beta adrenergic agonists, either synthetic such as Clenbuterol
or albuterol, or naturally occurring epinephrine and norepinephrine also elevate
cAMP and suppress calcium mediated protein breakdown [9]. Ephedrine elevates
cAMP directly by binding to beta receptors, and indirectly by increasing levels
of the body's naturally occurring hormone/neurotransmitter norepinephrine.
Newly published research also shows that Clenbuterol, besides inhibiting calcium
dependent proteolysis, also acts to block ATP-ubiquitin mediated protein breakdown
[10].
Finally, both the lysosomal breakdown of protein and the ATP-ubiquitin
proteolytic system are suppressed by insulin [11,12], so adequate carbohydrate
intake prior to, during and after strenuous exercise should help blunt these
pathways of protein breakdown.
Thus we have several strategies for reducing the breakdown of androgen receptor
proteins after exercise, some as simple as eating to elevate insulin, as well
as perhaps even increasing those receptor numbers with the use of certain anabolic
steroids such as oxandrolone.
References
MR, French DN, Vescovi JD, Silvestre R, Hatfield DL, Fleck SJ, Deschenes MR.
Androgen receptor content following heavy resistance exercise in men. J Steroid
Biochem Mol Biol. 2005 Jan;93(1):35-42.
Kraemer WJ, Gordon SE, Fleck SJ, Marchitelli LJ, Mello R, Dziados JE, Friedl
K,
Harman E, Maresh C, Fry AC. Endogenous anabolic hormonal and growth factor
responses to heavy resistance exercise in males and females. Int J Sports Med.
1991 Apr;12(2):228-35.
Hakkinen K, Pakarinen A. Acute hormonal responses to two different fatiguing
heavy-resistance protocols in male athletes. J Appl Physiol. 1993
Feb;74(2):882-7.
Kraemer WJ, Patton JF, Knuttgen HG, Marchitelli LJ, Cruthirds C, Damokosh A,
Harman E, Frykman P, Dziados JE. Hypothalamic-pituitary-adrenal responses to
short-duration high-intensity cycle exercise. J Appl Physiol. 1989
Jan;66(1):161-6.
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