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Biomedical subjects

S R Max

Publications and source records attributed to S R Max.

At least 55 records · Page 3Linked to original sources
PubMed1984

No effect of sex steroids on 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.

Animals↗
PubMed1984

Modulation of the cytosolic androgen receptor in striated muscle by sex steroids.

We studied the influence of orchiectomy (GDX) and steroid administration on the level of cytosolic androgen receptor in rat levator ani muscle and rat skeletal muscles (tibialis anterior and extensor digitorum longus). Androgen receptor binding to muscle cytosol was measured using [3H]methyltrienolone (R1881) as ligand, a 100-fold molar excess of unlabeled R1881 to assess nonspecific binding, and a 500-fold molar excess of triamcinolone acetonide to prevent binding to glucocorticoid and progestin receptors. Bound and free ligand were separated by column chromatography with Sephadex G-75. In levator ani muscles from intact animals (controls), maximum R1881 binding (Bmax), determined by Scatchard analysis, was 2.5 fmol/mg protein (Kd = 0.68 nM). Thirty days after GDX, Bmax increased to 500% of the control value, with no significant change in Kd (0.96 nM). Using saturating levels of R1881, Bmax was increased to 280% of the control value 12 h post-GDX, 600% at 14 days, 478% at 30 days, and 133% at 44 days. The increase in receptor binding was blocked by cycloheximide. Administration of Silastic capsules containing testosterone propionate 30 days post-GDX resulted in R1881 binding at the control level at 44 days. Surprisingly, administration of 17 beta-estradiol (E2) 30 days post-GDX resulted in increased (480%) R1881 binding. Thus, E2 may cause induction of the cytosolic androgen receptor in levator ani muscle from GDX rats; alternatively, the rate of receptor degradation may be altered. R1881 binding by skeletal muscle cytosol was increased 139% at 12 h, 212% on day 14, 220% on day 30, and 158% on day 44 with respect to the control value. Administration of testosterone propionate at 30 days caused R1881 binding to return to the control value by day 44, whereas E2 was without influence. The differences in response of levator ani and skeletal muscle receptors may account for the differential effects of sex steroids on these muscle types.

Animals↗
PubMed1983

Fiber type changes in denervated soleus muscles of the hyperthyroid rat.

The thyroid status of rats is known to influence the histochemical and biochemical myosin adenosine triphosphatase (M-ATPase) activity of the soleus muscle. In the hypothyroid state, denervated soleus muscles are not subject to that influence. Our experiments indicated that in the hyperthyroid state fibers of the denervated soleus muscle show a profound change from acid-stable M-ATPase positive to acid-stable M-ATPase negative. We concluded that this change was induced by the hyperthyroid state and was not neurally mediated.

Adenosine Triphosphatases↗
PubMed1983

Central core degeneration after tenotomy in soleus muscles of hyperthyroid rats.

Tenotomy of the rat soleus muscle is followed by a central degeneration of slow, fatigue-resistant muscle fibers. Previous experiments showed that fast, fatigable fibers of the gastrocnemius when transformed to slow, fatigue-resistant fibers by cross-reinnervation also develop lesions after tenotomy. The experiments described in this communication were carried out to discover whether the susceptibility of fibers to lesions was determined by their fiber type or the nature of their innervation. Rats were rendered hyperthyroid by the administration of sodium 3,3',5-triiodo-L-thyronine (T3) for 7 to 10 weeks. Tenotomy of the soleus muscles was then carried out and the experimental and contralateral muscles were removed and stained for myosin ATPase activity after a further 2 weeks. The hyperthyroid state of each animal was confirmed by the assay of succinate dehydrogenase activity of liver and the contralateral muscle. After acid preincubation, whole muscle fiber type counts of contralateral muscles showed a statistically significant change from a predominantly acid-stable population of fibers to acid-labile fibers. In addition, many fibers of intermediate staining properties were seen. When the experimental muscles were examined, all three varieties of fiber showed central degeneration. The nature of the fiber type change induced by T3 and the role that innervation might play in this is discussed. It was concluded that the susceptibility of fibers to the lesions that follow tenotomy is dependent on the nature of their innervation rather than their fiber type.

Animals↗
PubMed1983

Contractile properties of rat fast-twitch skeletal muscle during reinnervation: effects of testosterone and castration.

The isometric contractile properties of skeletal muscle were examined after nerve crush to establish the temporal sequence of recovery during reinnervation of normal, castrated, and testosterone-treated rats. Extensor digitorum longus muscles of male rats were studied in vivo 8 to 21 days after crushing the peroneal nerve 1 cm from the muscle. The earliest signs of functional reinnervation in normal animals were observed 8 to 9 days after nerve crush when faint muscle twitches with markedly prolonged twitch contraction times were recorded. By days 10 and 11, twitch tension was 9 to 20% of control, twitch contraction time was 149 to 183% of control, and tetanic tension was 4 to 9% of control values. The optimal frequency of stimulation was 58 to 64 Hz, the twitch:tetanus ratio was three times control values, and little or no posttetanic potentiation of twitch tension was observed. During the next 9 days there was a gradual return of all experimentally measured contractile properties toward control values; the relative rate of return was twitch tension greater than twitch contraction time greater than twitch:tetanus ratio greater than tetanic tension greater than optimal frequency of stimulation greater than posttetanic potentiation. Neither testosterone nor castration significantly altered either the rate or extent of functional reinnervation 8 to 21 days after nerve crush (P greater than 0.05). During this period the twitch:tetanus ratio for any given animal was highly correlated (r = 0.83, P less than 0.001) with the extent of functional recovery of neurally evoked muscle tension and was determined to be the most reliable index of the degree of muscle reinnervation. These data provide valuable baseline information for future studies of reinnervation of skeletal muscle.

Animals↗
PubMed1983

Cytosolic androgen receptor in skeletal muscle from normal and dystrophic mice.

The cytosolic androgen receptor was studied in skeletal muscle of normal mice and of mice with hereditary muscular dystrophy (129/ReJ-dy). Mouse muscle contains a cytosolic androgen receptor with high affinity (KD 0.6 nM) and low capacity (Bmax 3fmol/mg protein). Dystrophic muscle contains a receptor with similar binding properties. The receptors from muscle of dystrophic and normal mice bind to DNA-cellulose affinity columns and are eluted with similar patterns. The reported failure of androgens to alleviate the clinical signs of murine muscular dystrophy is probably not due to decreased androgen responsiveness of the affected muscles.

Animals↗
PubMed1983

Effect of denervation and reinnervation on oxidation of [6-14C]glucose by rat skeletal muscle homogenates.

We studied the effects of denervation and reinnervation of the rat extensor digitorum longus muscle (EDL) on the oxidation of [6-14C]glucose to 14CO2. The rate of 14CO2 production decreased dramatically following denervation, and the decrease became significant 20 days after nerve section. Prior to day 20, changes apparently reflected the decline of muscle mass. Decreased 14CO2 production was due to reduced capacity of the enzymatic system (apparent Vmax); there was no change in apparent affinity for glucose (apparent Km). Mixing experiments revealed that the loss of oxidative capacity following denervation is not caused by production of soluble inhibitors by degenerating muscle. Oxidative metabolism, as measured by 14CO2 evolution, recovered during reinnervation. Surprisingly, the specific activity in reinnervated muscles displayed an "overshoot" of approximately 50%, which returned to control by day 60, possibly reflecting increased energy demand by the growing muscle. The time-course of the denervation-mediated change indicates that altered oxidative capacity is secondary to events that initiate denervation changes in muscle. Nevertheless, diminished oxidative capacity may be of considerable metabolic significance in denervated muscle.

Animals↗
PubMed1983

Androgens enhance in vivo 2-deoxyglucose uptake by rat striated muscle.

Testosterone propionate causes a striking increase in in vivo uptake of 2-deoxyglucose by the levator ani muscle of immature male rats. Autoradiography showed the labeled 2-deoxyglucose to be uniformly distributed over the entire muscle. Liquid scintillation counting of whole muscles allowed quantification of 2-deoxyglucose uptake. After a single sc injection of testosterone propionate, no enhancement of 2-deoxyglucose uptake could be seen before 3.5 h, at which time uptake was increased 2-fold; maximum enhancement (4-fold) was attained at 12 h. 2-Deoxyglucose uptake remained elevated at twice the control value at 72 h. Muscle weight did not increase until sometime after 24 h; by 39 h, it was 50% greater than the control value; by 72 h, wet weight was double the control value. The effect of testosterone propionate probably is mediated by specific androgen receptors, since the administration of either 5 alpha-dihydrotestosterone or fluoxymesterone, potent androgens, caused severalfold increases in 2-deoxyglucose uptake in the levator ani muscle, while administration of 17 beta-estradiol, corticosterone, and etiocholanolone, an inactive metabolite of testosterone, did not. Furthermore, the effect of testosterone propionate was blocked by simultaneous administration of an androgen antagonist, cyproterone acetate. Testosterone propionate also enhanced uptake of 2-deoxyglucose in the bulbocavernosus (253% over control) and extensor digitorum longus muscles (150% over control), but not in the biceps brachii or soleus. Increased glucose uptake may be an important early step in the anabolic response of muscle to androgens.

Androgens↗
PubMed1982

Estrogen modulates neural control of muscle glucose 6-phosphate dehydrogenase.

Exogenously administered estrogens can enhance the rate of increase of glucose 6-phosphate dehydrogenase activity in rat extensor digitorum longus muscles following denervation. In this communication, we report that the effect of denervation on glucose 6-phosphate dehydrogenase activity is modified by variations in endogenous estradiol during the estrous cycle.

Animals↗
PubMed1982

Neural regulation of muscle glucose 6-phosphate dehydrogenase: effect of batrachotoxin and tetrodotoxin.

We tested the hypothesis that glucose 6-phosphate dehydrogenase (G6PD) activity in the rat skeletal muscle is regulated by putative axonally derived neurotrophic factors. This was accomplished by comparing the effects of nerve section and subperineural injection of batrachotoxin (BTX) or tetrodotoxin (TTX) on G6PD in rat extensor digitorum longus (EDL) muscle. BTX, an agent known to block nerve impulse conduction and axonal transport increased G6PD activity to 155% and 163% of control by days 2 and 4 after injection. Denervation of the EDL muscle by section of the peroneal nerve 10-20 mm from its entrance to the muscle caused G6PD activity to increase to 170% of control by day 1 and to 200% and 180% of control by days 2 and 4, respectively. The increase in enzyme activity after denervation and after subperineural injection of BTX was due in part to muscle inactivity resulting from blockade of nerve impulses. This conclusion is based upon the observation that subperineural injection of TTX at an identical site in the peroneal nerve caused a small but significant (30%) increase in G6PD activity after 4 days. Choline acetyltransferase (CAT) activity was assessed as a measure of the efficacy of blockade of slow axonal transport. Decreases in CAT activity following denervation or injection of BTX or TTX were parallel to increases in G6PD activity observed under these conditions. These results argue for a role of axonal transport in neural regulation of muscle G6PD, with a small contribution by neuromuscular activity.

Animals↗
PubMed1981

Cytosolic androgen receptor in regenerating rat levator ani muscle.

The development of the cytosolic androgen receptor was studied after degeneration and regeneration of the rat levator ani muscle after a crush lesion. Muscle regeneration appears to recapitulate myogenesis in many respects. It therefore provides a model tissue in sufficiently in large quantity for investigating the ontogenesis of the androgen receptor. The receptor in the cytosol of the normal levator ani muscle has binding characteristics similar to those of the cytosolic receptor in other androgen-sensitive tissues. By day 3 after a crush lesion of the levator ani muscle, androgen binding decreased to 25% of control values. This decrease was followed by a 4-5 fold increase in hormone binding, which attained control values by day 7 after crush. Androgen binding remained stable at the control value up to day 60 after crushing. These results were correlated with the morphological development of the regenerating muscle after crushing. It is concluded that there is little, if any, androgen receptor present in the early myoblastic stages of regeneration; rather, synthesis of the receptor may occur after the fusion of myoblasts and during the differentiation of myotubes into cross-striated muscle fibres.

Anal Canal↗
PubMed1981

Neural regulation of glucose 6-phosphate dehydrogenase in rat muscle: effect of denervation and reinnervation.

We tested the hypothesis that glucose 6-phosphate dehydrogenase (G6PD) in rat extensor digitorum longus (EDL) muscle is under neural control by studying changes in G6PD activity in EDL muscles following nerve crush-induced denervation and reinnervation. Changes in G6PD were correlated with choline acetyltransferase activity, as well as with neurological function, muscle weights, and muscle isometric twitch tension. The data show a dramatic increase in G6PD following denervation. The gradual recovery of enzyme activity toward normal levels correlates with the return of functional synaptogenesis manifested by the return of neurological function, choline acetyltransferase, and muscle twitch tension. We conclude, therefore, that muscle G6PD is under neural control. G6PD activity provides a facial biochemical indicator of muscle reinnervation.

Animals↗
PubMed1981

Selective carnitine palmitoyltransferase deficiency in fibroblasts from a patient with muscle CPT deficiency.

A 13-year-old boy developed cramps and myoglobinuria following exertion. Mitochondrial preparations from a skeletal muscle biopsy were deficient in carnitine palmitoyltransferase (CPT) activity when assayed by the hydroxamate and kinetic assays. The patient's fibroblasts were also deficient when assayed by the hydroxamate and kinetic assays, but not when tested by the DTNB (5,5'-dithiobis-[nitrobenzoic acid]) method. This disparity probably indicates a specific deficiency in fibroblasts of one of the two carnitine palmitoyltransferases, presumably CPT II.

Acyltransferases↗
PubMed1981

Effect of estrogen on denervated muscle.

The rate of increase of glucose 6-phosphate dehydrogenase activity in denervated rat extensor digitorum longus muscle shows sexual dimorphism. This phenomenon is further investigated in this report by assessing the effects of ovariectomy, hypophysectomy, hormone replacement therapy, and treatment with an estrogen antagonist , MER-25. The data demonstrate that physiologic doses of estrogens enhance the rate and extent of the increase in glucose 6-phosphate dehydrogenase activity after denervation. The data further indicate that aromatization of androgens may be a significant source of estrogen involved in hormonal modulation of the neural control of glucose 6-phosphate dehydrogenase and other processes in muscle. Furthermore, choline acetyltransferase activity, a marker for the neuromuscular synapse, decreased in rat extensor digitorum longus muscles after denervation, but was unaffected by ovariectomy.

Animals↗
PubMed1980

Effect of sex hormones on glucose-6-phosphate dehydrogenase in rat levator ani muscle.

We studied the influence of sex hormones using the hormone-sensitive levator ani muscle as a model tissue and glucose-6-phosphate dehydrogenase as an indicator of hormone action. Injection of testosterone or estradiol cause a 50% increase in the specific activity of glucose-6-phosphate dehydrogenase. The effect was dose-dependent, and was maximal at a dose of 2.5mg/100g body weight. Estradiol increased glucose-6-phosphate dehydrogenase as early as 8 h after injection, while testosterone required 12 h. Injection of estradiol on 2 successive days increased enzyme activity by 80%. The effect of estradiol was abolished by actinomycin D, suggesting enzyme induction. The results indicate a direct effect of estrogen on striated muscle.

Animals↗