No effect of sex steroids on compensatory muscle hypertrophy

1984 ◽  
Vol 56 (6) ◽  
pp. 1589-1593 ◽  
Author(s):  
S. R. Max ◽  
N. E. Rance
Keyword(s):  
Androgen Receptor ◽  
Sex Steroids ◽  
Muscle Hypertrophy ◽  
Specific Activity ◽  
Oxidative Capacity ◽  
Muscle Weight ◽  
Hormone Status ◽  
14Co2 Production ◽  
Synergistic Muscles ◽  
Compensatory Muscle Hypertrophy

We studied the effects of sex steroids on muscle weight and oxidative capacity of rat plantaris muscles subjected to functional overload by removal of synergistic muscles. Eight weeks after bilateral synergist removal, plantaris muscles were strikingly hypertrophic compared with unoperated controls. After this period, there were selective alterations in the ability of the muscles to oxidize three substrates of oxidative metabolism. Thus 14CO2 production from [6-14C]glucose and [2-14C]pyruvate was significantly reduced, whereas there was no alteration in 14CO2 production from beta-[3-14C]hydroxybutyrate. Succinate dehydrogenase specific activity was decreased in overloaded muscle. There was no effect of sex hormone status on any of these parameters. Finally, 30 days of functional overload did not influence cytosolic androgen receptor binding. These results are not consistent with the idea that sex steroids and functional overload act synergistically.

Modulation of IGF mRNA abundance during stretch-induced skeletal muscle hypertrophy and regression

1994 ◽  
Vol 76 (5) ◽  
pp. 2026-2030 ◽  
Author(s):  
S. M. Czerwinski ◽  
J. M. Martin ◽  
P. J. Bechtel
Keyword(s):  
Skeletal Muscle ◽  
Muscle Hypertrophy ◽  
Muscle Protein ◽  
Muscle Growth ◽  
Mrna Abundance ◽  
Mrna Levels ◽  
Muscle Weight ◽  
Igf I ◽  
Compensatory Muscle Hypertrophy ◽  
First Time

Increased load on a muscle (synergistic overload or stretch) results in muscle hypertrophy. The expression of insulin-like growth factor I (IGF-I) mRNA in rat skeletal muscle is increased during synergistic overload-induced hypertrophy. Although it has also been established that fasting animals lose muscle protein, it has been shown that compensatory muscle hypertrophy occurs in adult fasting rats that are undergoing a net loss of body weight. The purpose of this investigation was to determine whether a relationship exists between IGF-I mRNA levels and muscle growth and regression. This was accomplished by examining whether IGF-I mRNA levels were altered during muscle hypertrophy after stretch and regression and the effect of fasting on IGF-I mRNA levels during stretch-induced hypertrophy. Patagialis (PAT) muscle weights increased 13 and 44% at 2 and 11 days of stretch, respectively. However, after removal of the stretch stimulus on day 11, PAT weights began to decrease, reaching control weights by 18 days. During the first time point (2 days), PAT muscle IGF-I mRNA remained constant. IGF-I mRNA abundance was threefold greater than contralateral control levels by 11 days of stretch. IGF-I mRNA levels decreased but remained significantly above control levels throughout the regression of hypertrophy (13, 18, and 25 days). Fasting did not alter PAT muscle response to stretch. After 11 days of stretch, PAT muscle weight increased 60% compared with contralateral control muscles and IGF-I mRNA levels increased three-fold. This study supports a role for IGF-I in muscle hypertrophy but not muscle atrophy.

Compartmented pyruvate in perfused working heart

1985 ◽  
Vol 249 (3) ◽  
pp. H439-H449 ◽  
Author(s):  
R. Bunger
Keyword(s):  
Specific Activity ◽  
High Specific Activity ◽  
Inhibitory Effect ◽  
Quantitative Agreement ◽  
Myocardial Substrate ◽  
14Co2 Production ◽  
The Mean ◽  
Glycerol 3 Phosphate Dehydrogenase ◽  
Perfused Hearts ◽  
Working Heart

Pyruvate compartmentation and lactate dehydrogenase (LDH) were studied in isolated perfused working guinea pig hearts. The mean intracellular pyruvate (Pyr) contents increased with perfusate Pyr (0-2 mM) but varied only slightly with glucose (0-10 mM) and additional insulin (0.04-5 U/l), respectively. With 5-10 mM glucose plus 5 U/l insulin, but not with Pyr or lactate (Lac) as substrates, a near equilibrium between the LDH and the glycerol-3-phosphate dehydrogenase seemed to exist. Evidence for an inhibitory effect of Pyr on the activity of the LDH system of the perfused hearts was not obtained. With [U-14C]glucose as sole substrate, the specific activity of coronary venous Lac was near half that of precursor glucose. 14CO2 production was thus in quantitative agreement with rates of pyruvate oxidation that were determined as glucose uptake minus (Pyr + Lac) release. In contrast, with 0.2 mM [1-14C]Pyr plus 5 mM glucose, the ratio of 14CO2 production to specific activity of Lac overestimated Pyr oxidation judged from myocardial substrate balances and O2 uptake, respectively; here, at least three pools of [14C]HCO-3 and [14C]lac, respectively, were kinetically demonstrable during washout of trace amounts of 14C-labeled Pyr. Evidently, the specific activity of Lac was equivalent to that of mitochondrial oxidized Pyr provided [14C]glucose was the sole or major precursor of cellular pyruvate. However, exogenously applied [1-14C]Pyr of high specific activity seemed to induce intracellular formation of both a highly and lowly labeled Pyr; the latter Pyr compartment did not seem in ready equilibrium with the cell physiologically prevailing highly labeled Pyr pool.

Overload-induced androgen receptor expression in the aged rat hindlimb receiving nandrolone decanoate

2003 ◽  
Vol 94 (3) ◽  
pp. 1153-1161 ◽  
Author(s):  
Won Jun Lee ◽  
Joseph McClung ◽  
G. A. Hand ◽  
James A. Carson
Keyword(s):  
Androgen Receptor ◽  
Muscle Mass ◽  
Protein Concentration ◽  
Muscle Protein ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Nandrolone Decanoate ◽  
Muscle Weight ◽  
Aged Rat ◽  
Androgen Receptor Protein

This study's purpose was to examine whether functional overload with nandrolone decanoate (ND) administration increased muscle mass and steroid receptor concentration in aged rat soleus (Sol) and plantaris (Plan) muscle. ND (6 mg/kg body wt) was administered once a week for 4 wk, whereas control rats received sesame seed oil injections. Functional overload of the hindlimb Sol and Plan was induced by synergistic gastrocnemius muscle ablation at the beginning of the fourth week. Adult (5 mo of age) and aged rats (25 mo of age) were randomly assigned to four groups: control, overload, control-ND, and overload-ND. Seven days of functional overload increased adult Sol muscle mass 27%, whereas the aged Sol muscle mass did not change. The aged overloaded Sol muscle receiving ND significantly increased muscle weight by 35% and total muscle protein by 24%. Aged Plan muscle did not increase muscle weight with overload or ND treatment. Androgen receptor protein was induced by ND treatment and functional Ov, and combining the two treatments induced Sol androgen receptor protein concentration above either alone. Sol glucocorticoid receptor protein concentration increased in overload groups of both ages. ND administration can increase aged Sol muscle mass and protein content after 7 days of functional overload, and the cooperative induction of androgen receptor may be important for this response.

Fatty acid metabolism in hearts containing elevated levels of CoA

1986 ◽  
Vol 250 (3) ◽  
pp. H351-H359 ◽  
Author(s):  
G. D. Lopaschuk ◽  
C. A. Hansen ◽  
J. R. Neely
Keyword(s):  
Fatty Acid ◽  
Specific Activity ◽  
Pantothenic Acid ◽  
Acid Oxidation ◽  
Palmitate Oxidation ◽  
Triacylglycerol Hydrolysis ◽  
Chain Acyl ◽  
Apparent Decrease ◽  
Apparent Reduction ◽  
14Co2 Production

Palmitate metabolism was determined in isolated perfused hearts containing elevated levels of coenzyme A (CoA). CoA levels were elevated by perfusing hearts with Krebs-Henseleit buffer containing 0.1 mM cysteine, 0.2 mM dithiothreitol, 15 microM pantothenic acid, and no energy substrate. After 45 min, CoA levels had increased from 537 +/- 14 to 818 +/- 44 nmol/g dry wt. When these hearts containing high CoA were subsequently perfused as working hearts with buffer containing 11 mM glucose and 1.2 mM palmitate, long chain acyl CoA levels increased (94 +/- 5-305 +/- 6 nmol/g dry wt). Oxidation of exogenous palmitate (as measured by 14CO2 production from [U-14C]palmitate) was significantly depressed in hearts containing elevated CoA levels. This apparent reduction in fatty acid oxidation was not due to increased glucose or glycogen utilization. When the concentration of palmitate was decreased to 0.4 mM, acyl CoA levels increased much less, and the apparent rate of [14C]palmitate oxidation was unaffected by elevated CoA. Hearts containing high CoA also incorporated [14C]palmitate into triacylglycerols to a greater extent than did control hearts. To determine whether the apparent decrease in exogenous palmitate oxidation resulted from an increased utilization of unlabeled endogenous triacylglycerol fatty acid, [14C]palmitate specific activity was measured in myocardial acylcarnitine. The specific activity of this pool of fatty acid was similar in both control hearts and hearts containing elevated CoA. Thus dilution of the total cellular [14C]acyl carnitine by triacylglycerol hydrolysis was not sufficient to account for the decrease in [U-14C]palmitate oxidation. The possibility that a small pool of rapidly turning over acyl carnitine becomes dilated is discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Steroidal Androgens and Nonsteroidal, Tissue-Selective Androgen Receptor Modulator, S-22, Regulate Androgen Receptor Function through Distinct Genomic and Nongenomic Signaling Pathways

2008 ◽  
Vol 22 (11) ◽  
pp. 2448-2465 ◽  
Author(s):  
Ramesh Narayanan ◽  
Christopher C. Coss ◽  
Muralimohan Yepuru ◽  
Jeffrey D. Kearbey ◽  
Duane D. Miller ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Levator Ani ◽  
Reproductive Organs ◽  
Cross Reactivity ◽  
Levator Ani Muscle ◽  
Xenopus Laevis Oocyte ◽  
Muscle Weight

Abstract Androgen receptor (AR) ligands are important for the development and function of several tissues and organs. However, the poor oral bioavailability, pharmacokinetic properties, and receptor cross-reactivity of testosterone, coupled with side effects, place limits on its clinical use. Selective AR modulators (SARMs) elicit anabolic effects in muscle and bone, sparing reproductive organs like the prostate. However, molecular mechanisms underlying the tissue selectivity remain ambiguous. We performed a variety of in vitro studies to compare and define the molecular mechanisms of an aryl propionamide SARM, S-22, as compared with dihydrotestosterone (DHT). Studies indicated that S-22 increased levator ani muscle weight but decreased the size of prostate in rats. Analysis of the upstream intracellular signaling events indicated that S-22 and DHT mediated their actions through distinct pathways. Modulation of these pathways altered the recruitment of AR and its cofactors to the PSA enhancer in a ligand-dependent fashion. In addition, S-22 induced Xenopus laevis oocyte maturation and rapid phosphorylation of several kinases, through pathways distinct from steroids. These studies reveal novel differences in the molecular mechanisms by which S-22, a nonsteroidal SARM, and DHT mediate their pharmacological effects.

Role of the motor nerve in activity-induced enzymatic adaptation in skeletal muscle

1982 ◽  
Vol 242 (5) ◽  
pp. C272-C277 ◽  
Author(s):  
J. Henriksson ◽  
H. Galbo ◽  
E. Blomstrand
Keyword(s):  
Skeletal Muscle ◽  
Gastrocnemius Muscle ◽  
Tricarboxylic Acid Cycle ◽  
Motor Nerve ◽  
Oxidative Capacity ◽  
Control Group ◽  
Marker Enzyme ◽  
Muscle Weight ◽  
Enzymatic Adaptation ◽  
Gastrocnemius Muscles

The sciatic nerve was cut on one side in 11 male cats, and a piece of the nerve was removed. The cats were then divided at random into two groups, a stimulation group (S) of five cats and a control group (C) of six cats. Bilateral electrical stimulation (2 Hz) of the gastrocnemius muscle (directly or via the motor nerve) was carried out in the S cats 4 h/day, 3 days/wk for 4 wk. The voltage delivered was adjusted in each cat so that both gastrocnemius muscles lifted identical loads the same distance. The activity of the tricarboxylic acid cycle marker enzyme succinate dehydrogenase (SDH) per unit of muscle weight more than doubled in response to stimulation both in the intact and the denervated gastrocnemius muscle. Stimulation did not affect the activity of the glycolytic marker enzyme 6-phosphofructokinase (PFK) or muscle capillarization. Denervation resulted in pronounced (approx 50%) fiber atrophy, which was not prevented by the stimulation. It is concluded that the presence of the motor nerve per se is not necessary for an activity-induced adaptation of the oxidative capacity of skeletal muscle.

In vivo leucine oxidation at rest and during two intensities of exercise

1982 ◽  
Vol 53 (4) ◽  
pp. 947-954 ◽  
Author(s):  
P. W. Lemon ◽  
F. J. Nagle ◽  
J. P. Mullin ◽  
N. J. Benevenga
Keyword(s):  
Skeletal Muscle ◽  
Specific Activity ◽  
Muscle Metabolism ◽  
Weighted Average ◽  
Mixed Diet ◽  
Sprague Dawley ◽  
Tracer Dose ◽  
Sprague Dawley Rats ◽  
14Co2 Production

After ingestion of a mixed diet containing a tracer dose (10 muCi) of L-[1–14C]leucine (Leu), 32 male Sprague-Dawley rats (70–90 g) remained at rest (R) or completed 1 h exercise at 80 (E80) or 40% VO2max (E40). 14CO2 production was assessed for 6 h (exercise occurred from h 2 to 3). Four rats were killed at 2, 3, 4, and 6 h (R), at 3 and 6 h (E80), and at 6 h (E40). Determinations were 1) tissue specific activity dpm X mumol-1 from a) mixed skeletal muscle (gastrocnemius, soleus, quadriceps, and hamstrings) and b) liver and 2) radioactivity remaining in the gastrointestinal tract (GIT). Leu oxidized (mumol) was estimated (14 CO2 dpm X tissue sp act dpm-1 X mumol-1) independently from skeletal muscle and liver. Results were 1) 14CO2 production increased in both E80 and E40 compared with R (P less than 0.05), 2) E80 14CO2 increase was greater than E40 (P less than 0.05), 3) GIT absorption was reduced in E80 and E40 compared with R (P less than 0.05), and 4) exercise Leu oxidation (weighted average of tissue estimates) was 26% greater than R (P less than 0.05). The origin and site of the increased Leu oxidation cannot be determined from the present data; however, due to the magnitude of increase in skeletal muscle metabolism relative to other tissues during exercise, it is probable that skeletal muscle plays a significant role.

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