Therefore we are unable to estimate muscle protein net balance. This is particularly interesting given the facts that other indices of anabolic signaling, like the feeding-induced changes in the phosphorylation of Akt Thr , p70s6k Thr , and eEF2 Thr56 were similar in men and women.
An intriguing new finding was the marked and so far as we can tell previously unreported changes in the expression of myostatin and myoD with feeding, which are consistent with an acute nutritional control at the level of the nucleus of processes regulating muscle mass . Nevertheless, there was no apparent sex difference in these responses, which makes it unlikely that the feeding-induced changes in myostatin and myoD expression contributed to the blunted increase of MPS to feeding in women.
The feeding-induced increases in plasma glucose, insulin, and leucine concentrations were not different in men and women, which suggests that these also were not involved in the apparent anabolic resistance in women. It is possible, however, that there were sex differences in the insulin-stimulated increase in muscle nutritive blood flow which would differentially affect amino acid delivery to the muscle.
Although in young adults, the insulin mediated vasodilation is greater in women than in men  , there is evidence for a greater decline with aging in women compared with men in endothelium dependent dilation induced pharmacologically or by hypoxia  —  , which may abolish this difference at a more advanced age or even result in reduced flow in women.
However all these observations were for measures of bulk blood flow and no pertinent results exist, to our knowledge, for muscle microvascular perfusion . The impact of the sex hormone milieu on the anabolic effect of feeding in muscle is unknown largely due to a lack of data in the literature.
To our knowledge, no one has determined the effect of female sex steroids on the anabolic effects of amino acids or food in muscle; however, neither testosterone  nor oxandrolone  were found to exert an acute additive effect to the stimulatory effect of amino acids on MPS.
Our findings provide a potential mechanism that may help to explain the slower rate of muscle wasting during aging in women than in men  ,  — . Our arguments depend upon a number of observations. First, the data available from protein intakes in French  and North American  ,  older adults indicate that individuals between 65—80 y eat on average approximately 9—14 g protein at breakfast, 38—64 g protein at lunch, 19—33 g protein at dinner and 1. Thirdly, the results of a study of the circadian variations of amino acids during a h long study of the effects of 3 meals and two snacks suggested that the period of plasma essential amino acids being raised above the postabsorptive morning value was approximately 7 h .
Fourth, there is evidence that a sustained hyperaminoacidemia does not lead to a sustained increase in MPS, which returns to baseline values within approximately 2—2. Lastly, the relationship between amino acid availability and MPS is saturable both for orally delivered free amino acids  and orally delivered protein  , with excess essential amino acids being oxidized above delivery of approximately 15 g of protein per meal in young trained individuals  and probably even less in older adults .
Thus, we suggest that MPS proceeds at a rate corresponding closely to fed values in our study for approximately 6—8 h; for the remainder of the day, MPS would presumably operate at or near postabsorptive values. This then would result in a lower than average rate of MPS over the course of the day than in women. We recognize that a complete description of the mechanisms involved in nutritional regulation of muscle mass in the elderly will depend on information about the meal induced changes in muscle protein breakdown.
To date, there is no evidence that the sensitivity of MPS in older men and women to insulin released by feeding is different. Furthermore, in a study of 6 older men and 6 older women 68—70 y , who received two doses of insulin during hyperinsulinaemic, isoaminoacidemic clamps, leucine whole body Ra an index of whole-body proteolysis was not different between the sexes . Additional support comes from a study of 30 y old men and women, in which it was observed that the inhibitory effect of insulin on whole-body proteolysis assessed during a hyperinsulinemic, euglycemic, isoaminoacidemic clamp was not different between the sexes but, consonant with our results, in women there appeared to be an anabolic resistance to the stimulatory effect of insulin on whole-body protein synthesis .
In summary, we have demonstrated that there is significant sexual dimorphism in MPS and its control in older adults; a greater basal rate of MPS, operating over a large portion of the diurnal cycle, may be, at least in part, responsible for the slower loss of muscle in women than in men.
The authors wish to thank Nicole Wright for subject recruitment and technical assistance, and the study subjects for their participation. Performed the experiments: GS DV. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field.
Abstract Women have less muscle than men but lose it more slowly during aging. Introduction Adequate maintenance of muscle mass throughout life is important to preserve locomotor functions and diminish the risk of falling. Methods Subjects We studied 13 men and 16 women, aged 65 to 80 y; men and women were matched for age and body mass index Table 1.
Download: PPT. Experimental protocol Approximately two weeks before the protein metabolism study, subjects' total body fat-free mass FFM and appendicular muscle mass  were measured by using dual-energy X-ray absorptiometry Delphi-W densitometer, Hologic, Waltham, MA. Sample collection and storage Approximately 4 ml of blood was collected on each occasion. Sample processing and analyses Plasma glucose concentration was determined on an automated glucose analyzer Yellow Spring Instruments, Yellow Springs, OH.
Calculations Leucine rate of appearance Ra in plasma was calculated by dividing the rate of [5,5,5— 2 H 3 ]leucine infusion by the steady state plasma KIC TTR during basal, postabsorptive conditions and feeding. Statistical analysis All data sets were tested for normality. Plasma glucose, insulin, and leucine concentrations Basal plasma glucose and insulin concentrations were not different between men and women Table 3.
Whole-body leucine Ra Rates of leucine Ra during basal, postabsorptive conditions an index of whole-body protein breakdown and total leucine Ra during feeding were not different in men 2. Muscle protein synthesis The capacity for MPS i. Figure 2. Phosphorylation of anabolic signaling transduction molecules in muscle of men and women. Figure 3. Muscle mRNA expression of proteins involved in the regulation of muscle mass in men and women. Discussion In this study we uncovered marked sexual dimorphism between older men and women in a variety of aspects of muscle protein metabolism.
Acknowledgments The authors wish to thank Nicole Wright for subject recruitment and technical assistance, and the study subjects for their participation. References 1. Am J Clin Nutr — View Article Google Scholar 2. Zierler K Whole body glucose metabolism. Am J Physiol E— View Article Google Scholar 3. Horm Metab Res Suppl 41— View Article Google Scholar 4. Radegran G, Blomstrand E, Saltin B Peak muscle perfusion and oxygen uptake in humans: importance of precise estimates of muscle mass.
J Appl Physiol — View Article Google Scholar 5. Metabolism — View Article Google Scholar 6. View Article Google Scholar 7. View Article Google Scholar 8. View Article Google Scholar 9. Aging Clin Exp Res — View Article Google Scholar J Endocrinol 27— Buresova M, Gutmann E Effect of testosterone on protein synthesis and contractility of the levator ani muscle of the rat.
J Endocrinol — Growth — Annu Rev Nutr — Baillieres Clin Endocrinol Metab — J Muscle Res Cell Motil 21— Exp Physiol 87— J Clin Endocrinol Metab — Nature — Proud CG Signalling to translation: how signal transduction pathways control the protein synthetic machinery. Biochem J — J Clin Invest — Guttridge DC Signaling pathways weigh in on decisions to make or break skeletal muscle. Am J Med e— Roubenoff R Catabolism of aging: is it an inflammatory process?
J Neurol Neurosurg Psychiatry — Methods — J Physiol — Brodsky IG, Balagopal P, Nair KS Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men—a clinical research center study. Faseb J — JAMA — J Nutr S—S.
J Nutr — Garlick PJ The role of leucine in the regulation of protein metabolism. Amino Acids — Partridge T The current status of myoblast transfer. Neurol Sci S— Lind L, Fugmann A, Millgard J, Berne C, Lithell H Insulin-mediated vasodilatation, but not glucose uptake or endothelium-mediated vasodilatation, is enhanced in young females compared with males.
Clin Sci Lond — J Am Coll Cardiol — Sarabi M, Millgard J, Lind L Effects of age, gender and metabolic factors on endothelium-dependent vasodilation: a population-based study. J Intern Med — J Intern Med 29— Br J Nutr — In summary, we report an up-regulation of both stimulatory and inhibitory muscle growth regulatory genes and a faster muscle protein FSR in older, postmenopausal compared with carefully matched, younger, premenopausal women.
These age-related differences in basal muscle protein turnover in women do not appear to be explained by the age- and menopause-related changes in the plasma sex hormone milieu because we found that both testosterone 21 d of continuous delivery and progesterone replacement given for the equivalent of approximately three menstrual cycles stimulate muscle protein synthesis, whereas estradiol replacement given for the equivalent amount of time does not affect the rate of muscle protein synthesis.
The exact mechanisms by which progesterone stimulates muscle protein turnover remain to be elucidated but may be related to increased satellite cell activation as suggested by the increased MYOD1 expression.
We thank Sophie Julliand for help in subject recruitment, Dr Adewole Okunade and Jennifer Shew for their technical assistance, the staff of the Clinical Research Unit for their help in performing the studies, and the study subjects for their participation. This study was registered in clinicaltrials. Adult lean body mass declines with age: some longitudinal observations.
Google Scholar. Relation between whole-body and regional measures of human skeletal muscle. Am J Clin Nutr. Effect of testosterone on muscle protein synthesis in myotonic dystrophy. Ann Neurol. Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis. Am J Physiol. Testosterone injection stimulates net protein synthesis but not tissue amino acid transport.
Testosterone increases the muscle protein synthesis rate but does not affect very-low-density lipoprotein metabolism in obese premenopausal women. Am J Physiol Endocrinol Metab. Effect of testosterone on muscle mass and muscle protein synthesis. J Appl Physiol. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis.
Clin Endocrinol Oxf. Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. Effects of testosterone replacement in hypogonadal men. J Clin Endocrinol Metab. Long-term testosterone gel AndroGel treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men.
Effect of puberty on body composition. Curr Opin Endocrinol Diabetes Obes. Effects of estradiol and progesterone on body composition, protein synthesis, and lipoprotein lipase in rats. Sexually dimorphic effect of aging on skeletal muscle protein synthesis. Biol Sex Differ. Effects of estrogen replacement and lower androgen status on skeletal muscle collagen and myofibrillar protein synthesis in postmenopausal women.
Effect of administration of oral contraceptives on the synthesis and breakdown of myofibrillar proteins in young women. Scand J Med Sci Sports. Protein anabolic responses to a fed steady state in healthy aging. No effect of menstrual cycle on myofibrillar and connective tissue protein synthesis in contracting skeletal muscle. Is protein metabolism changed with obesity? The influence of the route of oestrogen administration on serum levels of cortisol-binding globulin and total cortisol.
Effects of the route of oestrogen administration on IGF-1 and IGFBP-3 in healthy postmenopausal women: results from a randomized placebo-controlled study. A randomized, open-label, crossover study comparing the effects of oral versus transdermal estrogen therapy on serum androgens, thyroid hormones, and adrenal hormones in naturally menopausal women.
Legerlotz K , Smith HK. Role of MyoD in denervated, disused, and exercised muscle. Muscle Nerve. Myofibrillar protein synthesis in myostatin-deficient mice. Stimulation of skeletal muscle myofibrillar protein synthesis, p70 S6 kinase phosphorylation, and ribosomal protein S6 phosphorylation by inhibition of myostatin in mature mice.
Long-term enhancement of skeletal muscle mass and strength by single gene administration of myostatin inhibitors. Regulation of myostatin activity and muscle growth. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. A more atherogenic serum lipoprotein profile is present in women with polycystic ovary syndrome: a case-control study. Testosterone and obesity in men under the age of 40 years. Harrison LL , Harari D. J Clin Pharmacol.
Pharmacokinetics of natural progesterone administered in the form of a vaginal tablet. Hum Reprod. Wheeler MJ. The determination of bio-available testosterone. Ann Clin Biochem. Measurement of total serum testosterone in adult men: comparison of current laboratory methods versus liquid chromatography-tandem mass spectrometry.
Measurement of human mixed muscle protein fractional synthesis rate depends on the choice of amino acid tracer. Physiol Genomics. Age-related changes in relative expression of real-time PCR housekeeping genes in human skeletal muscle. J Biomol Tech. Isolation of aminoacyl-tRNA and its labeling with stable-isotope tracers: Use in studies of human tissue protein synthesis. Myogenic gene expression at rest and after a bout of resistance exercise in young 18—30 yr and old 80—89 yr women.
Proteolytic gene expression differs at rest and after resistance exercise between young and old women. Oestrogen receptors mediate oestrogen-induced increases in post-exercise rat skeletal muscle satellite cells. Acta Physiol Oxf. Selective estrogen receptor-beta activation stimulates skeletal muscle growth and regeneration.
Stimulation of both estrogen and androgen receptors maintains skeletal muscle mass in gonadectomized male mice but mainly via different pathways. J Mol Endocrinol. Estrogen effects on skeletal muscle insulin-like growth factor 1 and myostatin in ovariectomized rats. Exp Biol Med Maywood. Estrogen influences satellite cell activation and proliferation following downhill running in rats.
J Anim Sci. Physical inactivity is a major contributor to ovariectomy-induced sarcopenia. Int J Sports Med. Estradiol treatment, physical activity, and muscle function in ovarian-senescent mice. Exp Gerontol. Progesterone stimulates cardiac muscle protein synthesis via receptor-dependent pathway.
Fertil Steril. Skeletal muscle adaptations to testosterone and resistance training in men with COPD. Suppression of testosterone does not blunt mRNA expression of myoD, myogenin, IGF, myostatin or androgen receptor post strength training in humans.
J Physiol. Sex differences in lipid and lipoprotein metabolism: it's not just about sex hormones. Androgen therapy induces muscle protein anabolism in older women. Short-term oxandrolone administration stimulates net muscle protein synthesis in young men. Age-related differences in fat-free mass, skeletal muscle, body cell mass and fat mass between 18 and 94 years. Eur J Clin Nutr. Weight stability masks sarcopenia in elderly men and women.
Fat-free and fat mass percentiles in healthy subjects aged 15 to 98 years. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign In. Advanced Search. Search Menu. Skip Nav Destination Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Materials and Methods.
Article Navigation. Smith , Gordon I. Oxford Academic. Jun Yoshino. Dominic N. David Bradley. Rachel E. Henry D. Anna C. Bettina Mittendorfer. Cite Cite Gordon I. Select Format Select format. Permissions Icon Permissions. Open in new tab Download slide. Table 1. P Value. Open in new tab. Table 2.
Protein synthesis was studied by means of 14C-leucine incorporation. It was found that anabolic steroid treatment resulted in an increased content of skeletal muscle protein: myosin, myofibrillar, and sarcoplasmic fractions. The activity of RNA-polymerase in skeletal muscle nuclei was increased.
The results indicated that in skeletal muscle there were androgen receptors which were binding sites for 3H-testosterone and anabolic steroids. A model for the anabolic steroid action on the regulation of protein synthesis in skeletal muscle was proposed. The majority of 'evidence' concerning the efficacy of anabolic steroids as performance enhancing agents is anecdotal.
In the main, experimental investigations have been poorly designed scientifically, clinically and statistically. The percentage of positive test results from IOC accredited laboratories has remained consistently low. However, athletes take their steroids during training and out-of-competition testing is not conducted in all countries, although international co-operation is now under consideration. Despite the lack of conclusive evidence, steroids users will continue to hold the view that their effects are efficacious and they are therefore unlikely to be persuaded to curtail their use.
Abstract Anabolic steroids are synthetic derivatives of testosterone modified to enhance the anabolic rather than the androgenic actions of the hormone.