Copyright 1996 by The Genmtological Society of America
Journal ofCieromoli>n\: BIOLOGICAL SCIENCES
19%. Vol. 5IA. No. 3. B2I4-B2I9
Growth Hormone Supplementation
Increases Skeletal Muscle Mass of Old Male
Fischer 344/Brown Norway Rats
Gregory D. Cartee,1 Erika E. Bohn,1 Brian T. Gibson,2 and Roger P. Farrar2
'Biodynamics Laboratory, University of Wisconsin, Madison.
-Department of Kinesiology, University of Texas, Austin.
Growth hormone (GH) supplementation can increase the body weight of old rats, but the individual tissues affected
were previously unidentified. Therefore, the masses of the heart, spleen, kidney, epididymal fat pads, and five skeletal
muscles were assessed in male Fischer 3441Brown Norway rats (9, 20, 31 months) injected with recombinant human
GH (0.7 mglkg) or vehicle twice daily for 10 days. Muscle composition (fiber type, protein concentration, dry weight/
wet weight ratio, citrate synthase activity) was also evaluated. Muscle mass was increased with GH treatment, and this
increment was undiminished in old age. Fiber type, protein concentration, and dry weight/wet weight ratio were
unaffected by GH. Citrate synthase activity declined in the plantaris and increased in the soleus with GH treatment.
GH supplementation elevated heart and spleen mass, but not fat pad or kidney weight. The data demonstrate that the
capacity for GH-induced hypertrophy of skeletal muscle, myocardium, and spleen is retained during old age.
loss of skeletal muscle mass has imporTHEtantage-related
functional implications. Consequently, there is
METHODS
much interest in identifying interventions that can attenuate
or reverse muscle atrophy in older individuals. Growth
hormone (GH) can be a potent stimulus for muscle growth in
young animals, so considerable attention has been devoted
to the possible influence of GH supplementation in the
elderly. Nonetheless, apparently only two published studies
have directly assessed the efficacy of GH for promoting
hypertrophy of individual muscles from older (26-27
months) rats (Ullman et al., 1990; Carmeli et al., 1993).
Ullman and colleagues reported that body weight was increased by 13% in old GH-treated rats, despite no increase in
the mass of the extensor digitorum longus (EDL) muscle,
indicating that GH treatment must have induced an increase
in the mass of other muscles or nonmuscle tissue. Carmeli et
al. (1993) observed no increase in body weight or gastrocnemius plus plantaris mass in older GH-treated rats. Each of
these earlier studies only examined one or two muscles and
no nonmuscle tissues from rats at a single age (i.e., 26-27
months), so they provide an incomplete view of the influence
of age on responsiveness to GH.
Therefore, the primary purpose of this study was to
characterize the influence of GH supplementation on the
mass of several skeletal muscles (i.e., gastrocnemius, plantaris, soleus, extensor digitorum longus, and brachioradialis) in male Fischer 344/Brown Norway rats at a wide range
of ages during adulthood (9, 20, and 31 months old). We
also evaluated several aspects of skeletal muscle composition (i.e., fiber type, protein concentration, dry weight/wet
weight ratio, and citrate synthase activity) and determined
the impact of GH administration on the mass of other tissues
that are responsive to GH treatment during youth (i.e., heart,
spleen, kidney, adipose tissue).
Treatment of rats. — Male Fischer 344/Brown Norway
Fl hybrid (F344/BN) rats of three ages (8-9, 19-20, or 3031 months) were obtained from Charles River Breeding
Laboratories. The age groups will be hereafter referred to as
the 9-, 20-, or 31-month-old groups. Upon arriving at
Madison, rats were housed in a facility isolated from contact
with other animals, and their caretakers did not come into
contact with any other rodents. The animal room was maintained at 23-24°C, with a relative humidity of 54-55% and a
light-on/light-off schedule of 6 a.m./6 p.m. Rats were provided with N1H-31M rodent diet (Agway Inc., Syracuse)
and water ad libitum until 4 p.m. on the day before they were
killed, when they were limited to 5 g of food. After equilibrating with their new environment for 10-20 days, rats
were randomly assigned to vehicle control or GH-treated
groups (before GH supplementation, body weights of agematched control and treated groups were not significantly
different). The rats received subcutaneous injections twice
daily, at 8 a.m. and at 3 p.m., for 10 consecutive days. The
GH group was injected with recombinant-derived human
GH (rhGH; Genentech, South San Francisco, CA; 0.7 mg/
kg body weight per injection) dissolved in sterile water
containing 0.9% benzyl alcohol (Abbott Laboratories, Chicago); the vehicle control group was injected with an equivalent volume of sterile water. Body weight was determined on
the day after the last injection when the rats were killed.
Food intake during the experimental period was evaluated by
measuring the food provided to the rats during the first 9 days
of treatment (i.e., not including the final day where food
intake was restricted) and subtracting the amount of food not
eaten. On the day following the last GH injection, animals
were anesthetized with pentobarbital sodium (60 mg/kg).
B214
EFFECTS OF GROWTH HORMONE ON MUSCLE
Several skeletal muscles (gastrocnemius, soleus, plantaris,
extensor digitorum longus, and brachioradialis), as well as
the heart, kidney, spleen, and epididymal fat pads, were
dissected out and weighed.
Determination of muscle protein concentration. — Portions of the gastrocnemius and soleus muscles were homogenized in ice-cold buffer containing 20 mM Hepes, 1 mM
EDTA, 250 mM sucrose (pH 7.4) at a 1:19 (wt:vol) ratio
using a Kontes Duall glass-glass tissue grinder. Protein
concentration in the homogenates was determined using the
spectrophotometric bicinchoninic assay (Smith et al., 1985).
Determination of fiber type composition. — After dissection and weighing, soleus and plantaris muscles that were
used for histochemistry were mounted on wooden holders,
frozen in isopentane cooled to the temperature of liquid N2,
and stored at -80°C until processed and analyzed. Transverse sections (8 |xm) were taken from the mid-belly of the
muscles using a cryostat microtome maintained at-20°C. To
distinguish type I, Ila, and lib fibers, serial sections were
mounted on coverslips and stained for myosin ATPase after
preincubation at pH 10.4, 4.54, or 4.50, respectively.
Stained sections were projected using a Bausch and Lomb
microprojector, and >1000 fibers were classified for each
muscle as previously described (Brooke and Kaiser, 1970).
Determination of muscle citrate synthase activity. —
Portions of the soleus and plantaris muscles were homogenized. Homogenates were analyzed for citrate synthase (CS)
activity at 30°C using a DU-6 UV-Visible Spectrophotometer (Beckman Instruments) (Srere, 1969).
Determination of tissue dry weight. — Portions of the
gastrocnemius and soleus muscles were weighed and then
dried in an oven. The muscles were then weighed on consecutive days until a stable weight was obtained (i.e., dry
weight). Dry weight was also determined for the heart,
spleen, and kidney.
Statistical analysis. — The data were analyzed using twoway analysis of variance employing the General Linear
Models Procedure (SAS; Cary, NC).
B215
sively greater with advancing age (p < .0001), and GH
treatment led to a significant (/; < .0002) elevation in body
weight (432.5 ± 4.6 vs 463.3 ± 4.9, 9-month-old; 515.1
± 6.2 vs 545.8 ± 9 . 1 , 20-month-old; 552.8 vs 578.7 ±
12.5, 31-month-old). The relative GH-induced increase in
body weight was 7%, 6%, and 5% in the 9-, 20-, and 31month-old rats, respectively. Food intake (g) was not significantly affected by age or GH treatment (control vs GH:
21.9 ± 1.0vs22.2 ± 0.6, 9-month-old; 20.6 ± 0.7 vs 20.8
± 1.0, 20-month-old; 24.3 ± 1.5 vs 20.8 ± 0.6, 31month-old).
Muscle weight and protein concentration. — A significant effect of age was found on the weight of every muscle
studied (Table 1). The relative age-related decrease in the
weight (31-month-old control vs apparent peak mass at 9- or
20-month-old controls) varied among the skeletal muscles:
gastrocnemius (25%), plantaris (22%), soleus (13%), EDL
(15%), and brachioradialis (10%). Treatment with GH led to
a significant increase in the weight of each muscle compared
to vehicle-treated controls. With the exception of the brachioradialis muscle, the magnitude of the increment above agematched control values tended to be greatest in the oldest
rats. Gastrocnemius and soleus protein concentration (Table
2) was not significantly affected by age or GH treatment.
Tissue weights and wetIdry weight ratios. — The wet
weights of the spleen, heart, kidney, and epididymal fat pad
each increased significantly Q? < .0001) with advancing age
(Table 3). Treatment with GH significantly increased spleen
{p < .0001) and heart {p < .005) wet weight in each age
group, compared to vehicle-treated controls, by 15—28%
and 6-8%, respectively. The kidney and epididymal fat pad
weights from the GH-treated groups did not differ from agematched control groups. There were no significant effects of
age or GH treatment on the dry weight/wet weight ratios for
the gastrocnemius, soleus, heart, or kidney, demonstrating
the hypertrophy was not attributable to edema (Table 4). The
GH-treated groups were characterized by a statistically
significant {p < .05) decrease in dry weight/wet weight ratio
for the spleen, but the magnitude of this decrement (<5%)
was quite small compared to the relative increase in spleen
wet weight (15-28%).
RESULTS
Body weight and food intake. — As previously reported
(Cartee and Bohn, 1995), body weight (g) became progres-
Muscle fiber type composition. — There was no significant effect of age or GH treatment on the fiber type composition of the soleus (Table 5). In the plantaris, a significant
Table 1. Effect of Age and Growth Hormone Treatment on Skeletal Muscle Weight
9 Months
20 Months
31 Months
Main Effects
Vehicle
Control
Growth
Hormone
Vehicle
Control
Growth
Hormone
Vehicle
Control
Growth
Hormone
Gastrocnemius
Plantaris
Soleus
EDL
2287 ± 38
464 ± 6
2349 ± 55
465 ± 15
195 ± 5
206 ± 3
203 ± 6
210 ± 7
2209 ± 27
457 ± 6
214 ± 5
2271 ±54
477 ± 9
221 ± 7
1722 ± 51
363 ± 13
186 ± 9
1937 ± 76
400 ± 15
206 ± 7
205 ± 9
218 ± 8
175 ± 8
196 ± 10
/; <
p<
p<
p<
Brachioradialis
323 ± 6
361 ± 8
345 ± 8
391 ± 3
312 ± 8
348 ± 10
p < .0001
Age
.0001
.0001
.005
.005
Growth
Hormone
Interaction
Age x Growth
Hormone
/; < .01
p < .05
n.s.
n.s.
/; < .05
n.s.
n.s.
p<.05
/J
< .0001
n.s.
Notes: Values (means ± SE) are expressed as mg; n - 6-10 muscles per group. EDL = extensor digitorum longus. n.s. = nonsignificant (/; > .05).
CARTEEETAL.
B216
Table 2. Effect of Age and Growth Hormone Treatment on Skeletal Muscle Protein Concentration
Gustrocnemius
Soleus
31 Months
20 Months
9 Months
Main Effects
Vehicle
Control
Growth
Hormone
Vehicle
Control
Growth
Hormone
Vehicle
Control
Growth
Hormone
178.5 ± 7.5
160.0 ± 9.6
170.3 ± 10 .7
162.0 ± 8 .8
170.9 ± 6.6
147.1 ± 7.2
172.7 ± 5.7
163.0 ± 6.4
155.3 ± 9.8
148.1 ± 11.2
163.3 ± 10.3
144.7 ± 5.5
Interaction
Age
Growth
Hormone
Age x Growth
Hormone
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
Notes: Values (means ± SE) are expressed as mg protein per g wet weight; n = 6 per group, n.s. = nonsignificant (/; > .05).
Table 3. Effect of Age and Growth Hormone Treatment on Tissue Weight
20 Months
9 Months
Growth
Hormone
Vehicle
Control
Heart
Spleen
Kidney
Epididymal fat
1045.7
675.2
1602.9
3395.1
±
±
±
±
15.7
16.3
76.0
107.6
1135.1
836.8
1564.2
3489.0
± 22.8
± 23.4
± 46.2
± 148.9
Growth
Hormone
Vehicle
Control
1220.6 ± 32.4
769.5 ± 18.6
1855.9 ± 75.5
6012.6 ± 275.4
Main Effects
31 Months
1317.2
987.0
1851.3
5656.7
±
±
±
±
36.1
21.1
84.2
262.6
Vehicle
Control
Growth
Hormone
1372.3 ± 58.5
1459.8 ± 39.6
1082.3 ± 57.1
1811.4 ± 63.5
6760.6 ± 544.3
1245.4 ± 59.4
1957.5 ± 42.7
6207.0 ± 395.4
Age
P<
P<
P<
P<
.0001
.0001
.0001
.0001
Interaction
Growth
Hormone
Age x Growth
Hormone
/><.005
/J < .0001
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
Notes: Values (means ± SE) are expressed as mg; n - 7-10 per group, n.s. = nonsignificant (p > .05).
Table 4. Effect of Age and Growth Hormone Treatment on Tissue Dry WeightiWet Weight Ratio
20 Months
9 Months
Vehicle
Control
Gastrocnemius
Soleus
Heart
Spleen
Kidney
0.249
0.251
0.253
0.283
0.254
±
±
±
±
±
0.004
0.014
0.004
0.005
0.006
Growth
Hormone
0.251
0.246
0.253
0.275
0.256
±
±
±
±
±
0.003
0.008
0.005
0.003
0.004
Vehicle
Control
0.250
0.265
0.252
0.284
0.245
± 0.002
± 0.018
± 0.001
± 0.002
±0.011
31 Months
Growth
Hormone
0.244
0.238
0.257
0.286
0.259
± 0.005
± 0.012
± 0.006
± 0.004
± 0.001
Vehicle
Control
0.253
0.243
0.248
0.284
0.269
±
±
±
±
±
0.009
0.006
0.005
0.004
0.005
Main Effects
Growth
Hormone
0.240
0.243
0.245
0.271
0.263
±
±
±
±
±
0.005
0.014
0.003
0.004
0.001
Interaction
Age
Growth
Hormone
Age x Growth
Hormone
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
p < .05
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
Notes: Values (means ± SE) are expressed as the dry weight (mg) -r wet weight (mg); n = 3 - 1 0 per group, n.s. = nonsignificant (p > .05).
age-related increase (/; < .005) in the percentage of type I
libers occurred, and this effect was not reversed by GH
treatment.
lar and intracellular compartments as determined by mannitol space (Cartee and Bonn, 1995). The GH-induced increase in muscle mass in old rats, along with no decrement in
protein concentration or dry weight/wet weight ratio, is
consistent with the observation that 8 days of GH suppleMuscle citrate synthase (CS) activity. — There was a significant main effect of age (p < .002) on soleus CS activity,
mentation significantly enhances the rate of protein synthesis
but no significant age effect was evident for the CS of the
in skeletal muscle from old male rats (Sonntag et al., 1985).
plantaris muscle (Table 6). GH treatment led to a significant
Assuming that the remainder of the musculature responded
{]-> < .01) decline in plantaris CS activity, and a significant (p in a fashion similar to the muscles that we studied, skeletal
< .01) increase in soleus CS activity.
muscle would account for a substantial portion of the GHinduced body weight gain.
DISCUSSION
Two earlier studies reported no effect of rhGH on muscle
The magnitude of the effect of GH on skeletal muscle
mass of older female rats. Ullman and coworkers (1990)
mass was undiminished in old age. In the oldest group, GH
found no increase in EDL mass of 26-month-old female
Sprague-Dawley rats treated with rhGH (4 IU injected daily
treatment led to a 10-13% increase in weight of every
for 10 weeks). Carmeli et al. (1993) observed no rhGHmuscle studied; in the middle-aged group, GH treatment led
induced (0.6 mg/kg, subcutaneously injected on alternate
to a 3-13% increase; in the youngest group, only the brachdays for 3 weeks) change in muscle (gastrocnemius and
ioradialis (12% increase) had an increase of >5%. Muscle
plantaris) or body weight of 26-month-old female Wistar
protein concentration and dry weight/wet weight ratio were
rats. Carmeli and colleagues did find that GH administration
stable with GH supplementation, demonstrating that the
attenuated the muscle weight loss in immobilized (casted)
increase in muscle mass was not attributable to tissue edema.
hindlimb muscles of the old rats. The absence of young
In addition, we recently reported that GH treatment did not
controls undergoing identical GH supplementation in each
alter the distribution of muscle water between the extracellu-
B217
EFFECTS OF GROWTH HORMONE ON MUSCLE
Table 5. Effect of Age and Growth Hormone Treatment on Skeletal Muscle Fiber Type Composition
31 Months
20 Months
9 Months
Main Effects
Interaction
Age
Growth
Hormone
Age x Growth
1 lormone
13.0 ± 1.8
10.3 ± 1.2
76.7 ± 1.6
/; < .005
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
94.6 ± 2.0
5.3 ± 2.1
0.1 ± 0 . 1
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
n.s.
Vehicle
Control
Growth
Hormone
Vehicle
Control
Growth
Hormone
Vehicle
Control
Growth
Hormone
Plantaris*
Type 1
Type IIA
Type IIB
9.4 ± 1.3
15.3 ± 1.5
75.1 ± 1.2
7.9 ± 0.9
14.2 ± 1.9
77.9 ± 2.6
11.5 ± 1.3
22.6 ± 7.6
65.8 ± 7.9
10.6 ± 1.2
17.2 ± 5.8
72.1 ± 4.8
16.9 ± 3.2
16.0 ± 2.9
67.1 ± 5.1
Soleus"
Type 1
Type IIA
Type IIB
93.5 ± 2.1
6.3 ± 1.9
0.1 ± 0 . 1
95.8 ± 0.4
4.2 ± 0.4
0
92.6 ± 1.6
7.3 ± 1.6
0.1 ± 0 . 1
96.9 ± 0.9
3.1 ± 0.9
0
95.4 ± 1.9
4.5 ± 1.8
0.1 ± 0 . 1
Notes: Values (means ± SE) are expressed as percentage of fibers, n.s. = nonsignificant^? > .05).
"Plantaris. n = 4-6 muscles per group.
b
Soleus, n = 2-4 muscles per group.
Table 6. Effect of Age and Growth Hormone Treatment on Skeletal Muscle Citrate Synthase Activity
Plantaris
Soleus
27.45 ± 2.02
28.71 ± 1.53
31 Months
20 Months
9 Months
Vehicle
Control
Growth
Hormone
24.72 ± 1.42
29.68 ± 1.67
Vehicle:
Control
27.07 ± 1. 39
29.41 ± 1. 75
Growth
Hormone
22.58 ± 1.49
35.84 ± 1.96
Vehicle
Control
25.32 ± 1.99
23.57 ± 0.99
Main Effects
Growth
Hormone
21.06 ± 1.91
28.38 ± 1.42
Interaction
Age
Growth
Hormone
Age x Growth
Hormone
n.s.
/; < .002
/; < .01
/ ; < .01
n.s.
n.s.
Notes: Values (means ± SE) expressed as (xmol # min" u g"'; // = 6-10 rats per group, n.s. nonsignificant (/; > .05).
of the earlier studies prevents an unambiguous evaluation of
the influence of age on GH-induced changes in muscle mass.
However, in an earlier study, Ullman and Oldfors (1989)
reported a 24% increase in the EDL weight of 5-month-old
female Sprague-Dawley rats injected with rhGH (4 IU daily
for 36 days). Unlike our results, these previously published
findings suggested that, with advancing age, skeletal muscle
becomes resistant to the growth promoting effects of GH.
The explanation for the absence of a GH effect on the
muscle mass of older rats in earlier studies is uncertain.
Gender might be a factor because female rats were used in
the two studies that did not find a GH-induced increase in
muscle mass during old age, whereas we studied males.
Other differences in the studies (e.g., rat strain and age;
duration, frequency, or dose of the GH injections) might also
be important. The experiments failing to observe GHinduced muscle hypertrophy in older rats used a single daily
injection or a single injection on alternate days. GH is
normally secreted in a pulsatile fashion, and greater growth
has been repotted with two to four daily injections compared
to a single daily injection (Jansson et al., 1982). For this
reason, the rats in this study were injected twice daily, in the
morning and the afternoon. It is notable that Sonntag et al.
(1985) studied male rats injected twice daily with GH when
they documented a GH-induced enhancement in muscle
protein synthesis during old age.
Previously, we reported that the serum insulin-like growth
factor-I (IGF-I) concentration did not change with age in
control animals used for this study (controls: 9-month =
4.24; 20-month = 4.40; 31-month = 4.25 U/ml), and IGF-I
levels were approximately doubled by GH supplementation
at every age (GH: 9-month = 9.73; 20-month = 9.52; 31month = 8.98 U/ml) (Cartee and Bohn, 1995). Since
skeletal muscle expresses receptors for both GH and IGF-I,
muscle hypertrophy could potentially be directly mediated
by GH or indirectly mediated by IGF-I. However, Guler et
al. (1988) demonstrated that infusion of rhIGF-I does not
stimulate muscle growth in hypophysectomized rats, suggesting that the hypertrophy depends on the presence of GH.
Although aging has repeatedly been shown not to alter the
fiber type composition of the soleus or EDL (Eddingeret al.,
1985; Florini and Ewton, 1989; Brown et al., 1992), Holloszy et al. (1991) found that the percentage of type Ifibersof
the plantaris was higher in 28- to 30-month-old rats compared
to 9-month-old Long Evans rats. Consistent with these earlier
investigations, we observed no effect of age on soleus fiber
type composition and a significant age-related increase in the
percentage of type I fibers of the plantaris. Also, in agreement with the findings of Florini and Ewton (1989), the fiber
type composition of the soleus was unaffected by GH administration. Furthermore, GH supplementation did not reverse
the age-related increase in type I fibers found in the plantaris.
This lack of difference in fiber type composition, as we
determined using the myosin ATPase technique (Brooke and
Kaiser, 1970), does not eliminate the possibility that fibers
contain more than one isoform of myosin heavy chain.
Skeletal muscle CS activity has been found to decline with
advancing age in various skeletal muscles from F344 (Cartee
and Farrar, 1987), Long Evans (Holloszy et al., 1991), and
Wistar (Hansford and Castro, 1982) rats. Similarly, in the
F344/BN rats from this study, soleus CS activity was ~ 17%
lower in the 31-month-old group compared to the 9- and 20-
B218
CARTEEETAL.
month-old control groups. However, plantaris CS activity
was not significantly affected by age in F344/BN rats.
Few studies have evaluated the influence of GH on the
activity of mitochondrial enzymes in skeletal muscle. Administration of rhGH (556 fxg/day by osmotic minipumps for 10
days) to male Sprague-Dawley rats (35 days old) did not
affect succinate dehydrogenase activity of the soleus (Jiang et
al., 1993); this protocol also did not influence soleus mass.
Unexpectedly, the GH supplementation elicited divergent
effects on the CS activity in the two muscles that we studied:
an increase was observed for the soleus and a decline occurred in the plantaris. Although the explanation for these
findings is uncertain, it is apparent that GH treatment can alter
the metabolic profile of muscles, even when fiber type composition and total protein concentration are unaffected. Along
these lines, we recently reported that GH treatment regimen
used in this study can reduce the glucose transport activity of
skeletal muscle (Cartee and Bohn, 1995).
The growth-promoting influence of GH supplementation
varied among the tissues studied. Spleen mass of the GHtreated rats was 15-28% higher than the values for agematched controls, greatly exceeding the relative elevation in
body weight (5-7%). This observation is consistent with
earlier results in younger rats (Ullman and Oldfors, 1989).
GH treatment led to an increase (6-9%) in myocardial mass
compared to control values, and the magnitude of the increase that was roughly proportional to the effect on body
weight. Comparable observations have been reported for
younger rats (Ullman and Oldfors, 1989; Rubin et al.,
1990). Kidney weight was unaltered in the GH-supplemented groups, a finding that differs from published data for
young rats: kidney weight has been reported to increase
roughly in proportion to the increases for body weight and
heart weight (Greenbaum and Young, 1953; Ullman and
Oldfors, 1989). IGF-I, independent of GH, can promote
hypertrophy of the spleen, heart, and kidney of young rats
(Clark et al., 1985; Guleret al., 1988). As described above,
the circulating IGF-I levels were substantially elevated in the
animals from the current study. In this light, the failure for
GH to promote renal hypertrophy might be indicative of a
tissue-specific resistance to IGF-1 action compared to the
younger animals from earlier studies.
GH can stimulate lipolysis (Hart et al., 1984) and reduce
body fat stores in young rats (Batchelor and Stern, 1973;
Crist et al., 1988), so it seemed possible that a GH-induced
decline might occur in the mass of the epididymal fat pad.
Although there was a trend for reduced epididymal fat pad
weight in the older animals, there was no significant GH
effect. It remains possible that the mass of other fat depots
was reduced by GH supplementation.
In younger animals, the growth-promoting action of GH
can occur independent of altered food intake, indicating
that the weight gain is caused by increased feed efficiency;
high doses of exogenous GH can stimulate hyperphagia
concomitant with even greater weight gain (Byatt et al.,
1993). In this study, the increased body weight in the GHtreated rats occurred without any change in food intake,
regardless of age.
In conclusion, we have identified several of the individual
tissues (i.e., skeletal muscle, heart, and spleen) that contrib-
ute to the increased body weight in adult, middle-aged, and
old male F344/BN rats after a brief period of GH administration. GH supplementation led to an increase in the mass of
the skeletal muscles studied, and the magnitude of this
increment was unattenuated by advancing age. The results
suggest that an increase in skeletal muscle mass accounted
for a large portion of the greater body weight in the GHtreated rats.
ACKNOWLEDGMENTS
This research was supported by an award from the American Federation
lor Aging Research and National Institute on Aging grant AG-10026 (G. D.
Cartee).
We are grateful for the excellent technical assistance of Carol BriggsTung, Mindy Huiting, Myriah Mathisen, and Deborah Nucatola. Genentech generously provided the recombinant-derived human growth hormone.
Address correspondence to Dr. Gregory D. Cartee, Biodynamics Laboratory, University of Wisconsin, 2000 Observatory Drive, Madison, Wl
53706.
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Received June 28, 1995
Accepted September 19, 1995
Scheie Eye Institute
Department of Ophthalmology
University of Pennsylvania Health System
presents
THE 11TH ANNUAL SYMPOSIUM ON LOW VISION
Saturday, June 15, 1996
8:00 a.m. - 5:00 p.m.
TOPICS INCLUDE:
Current Therapeutic Trials for Macular Degeneration
Hereditary Retinal Degeneration - Present and Future
Physiatry and Vision Rehabilitation
Occupational Therapy and Vision Rehabilitation
Coordinating Low Vision Rehabilitation with
Occupational Therapy
Workshops:
Problem Solving Techniques in Vision Rehabilitation
Evaluation and Management of Homonymous
Hemianopsias
The Visually Impaired Child
The Auto-Focus Telescope - It's Here!
What's New and Exciting in Low Vision Rehabilitation
Fitting and Prescribing Telescopes
COURSE FACULTY:
Chairman -Janet DeBerry Steinberg, O.D.
Richard Brilliant, O.D.
Henry Greene, O.D.
Samuel G. Jacobson, M.D, Ph.D.
Alexander J. Brucker, M.D.
Keith Robertson, M.D.
Abbe Dantzig, OTR/L
Bruce Rosenthal, O.D.
Paul Freeman, O.D.
CME Credits:
Fee:
Location:
Information:
6 credit hours in Category 1
$125 for practicing O.D./M.D./D.O. (includes breakfast, luncheon & coffee breaks)
Scheie Eye Institute,
51 No. 39th Street,
Philadelphia, PA 19104
Diane Lutz, CME Coordinator
(215) 662-8141