Role of ovarian hormones in the regulation of protein metabolism in women: effects of menopausal status and hormone replacement therapy

2006 ◽  
Vol 291 (3) ◽  
pp. E639-E646 ◽  
Author(s):  
Michael J. Toth ◽  
Cynthia K. Sites ◽  
Dwight E. Matthews
Keyword(s):  
Postmenopausal Women ◽  
Protein Metabolism ◽  
Protein Turnover ◽  
Hormone Replacement ◽  
Menopausal Status ◽  
Ovarian Hormones ◽  
Hormone Deficiency ◽  
Whole Body ◽  
Protein Breakdown ◽  
Body Protein

The age-related decline in fat-free mass is accelerated in women after menopause, implying that ovarian hormone deficiency may have catabolic effects on lean tissue. Because fat-free tissue mass is largely determined by its protein content, alterations in ovarian hormones would likely exert regulatory control through effects on protein balance. To address the hypothesis that ovarian hormones regulate protein metabolism, we examined the effect of menopausal status and hormone replacement therapy (HRT) on protein turnover. Whole body protein breakdown, oxidation, and synthesis were measured under postabsorptive conditions using [13C]leucine in healthy premenopausal ( n = 15, 49 ± 1 yr) and postmenopausal ( n = 18, 53 ± 1 yr) women. In postmenopausal women, whole body protein turnover and plasma albumin synthesis rates (assessed using [13C]leucine and [2H]phenylalanine) were also measured following 2 mo of treatment with oral HRT (0.625 mg conjugated estrogens + 2.5 mg medroxyprogesterone acetate, n = 9) or placebo ( n = 9). No differences in whole body protein breakdown, oxidation, or synthesis were found between premenopausal and postmenopausal women. Protein metabolism remained similar between groups after statistical adjustment for differences in adiposity and when subgroups of women matched for percent body fat were compared. In postmenopausal women, no effect of HRT was found on whole body protein breakdown, synthesis, or oxidation. In contrast, our results support a stimulatory effect of HRT on albumin fractional synthesis rate, although this did not translate into alterations in circulating albumin concentrations. In conclusion, our results suggest no detrimental effect of ovarian hormone deficiency coincident with the postmenopausal state, and no salutary effect of hormone repletion with HRT, on rates of whole body protein turnover, although oral HRT regimens may increase the synthesis rates of albumin.

scholarly journals A Whole-Grain Diet Improves Whole-Body Protein Turnover Compared to a Macronutrient-Matched Refined-Grain Diet in Adults with Overweight/Obesity

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1661-1661
Author(s):  
Jacob Mey ◽  
John Kirwan
Keyword(s):  
Protein Synthesis ◽  
Protein Metabolism ◽  
Protein Turnover ◽  
Whole Grains ◽  
Whole Body ◽  
Protein Breakdown ◽  
Whole Grain ◽  
Protein Kinetics ◽  
Body Protein ◽  
Fasted State

Abstract Objectives We investigated the effect of consuming a whole-grain diet on whole-body protein metabolism compared to a macronutrient-matched refined-grain diet in adults with overweight/obesity using labelled amino acids (ClinicalTrials.gov Identifier: NCT01411540). Methods We conducted a randomized, controlled crossover trial in 14 adults with overweight/obesity (age: 40 ± 7 yrs, BMI: 33 ± 5 kg/m2) in which isocaloric, macronutrient-matched whole-grain (WG) and refined-grain (RG) diets were fully provided for two 8-week periods (with a 10-week washout period). Diets differed only in the inclusion of whole grains (50 g/1000 kcal). Body composition was measured via DEXA. Whole-body protein kinetics were assessed before and after each diet in the fasted state (13C-Leucine, primed, constant infusion) and over 24 hours (15N-Glycine, bolus). Protein kinetics were normalized to fat-free mass (FFM). Results Both diets resulted in mild weight loss (WG: −2.0 ± 2.5 kg; RG: −2.9 ± 3.3 kg; both P = 0.01 compared to baseline). Fasted-state leucine kinetics revealed greater protein synthesis (WG: 205 ± 61 µmol/kgFFM/hr; RG: 178 ± 36 µmol/kgFFM/hr; P = 0.04) and protein breakdown (WG: 235 ± 68 µmol/kgFFM/hr; RG: 203 ± 40 µmol/kgFFM/hr, P = 0.03) on a WG vs RG diet. This resulted in a more negative fasted-state net balance on a WG diet (WG: −30 ± 8 µmol/kg/hr; RG: −25 ± 6 µmol/kg/hr, P = 0.02). In contrast, 24-hour whole-body protein turnover measured by the end-product method (15N-Glycine), revealed greater protein synthesis (WG: 316 ± 135 mg protein/kgFFM/hr; RG: 250 ± 94 mg protein/kgFFM/hr) with no difference in protein breakdown, yielding a more positive 24-hr net balance on a WG diet (WG: 31 ± 21 mg protein/kgFFM/hr; RG: 10 ± 34 mg protein/kgFFM/hr). Conclusions A whole-grain diet increases whole-body leucine flux and results in a greater 24-hr net protein balance in adults with overweight/obesity compared to a refined-grain diet. This trial suggests whole-grains have an independent effect on protein metabolism and may benefit adults with overweight/obesity. Funding Sources This research was supported by the NIH (UL1 RR024989, T32DK007319 (JPK); T32AT004094 (JTM – trainee)) and an investigator-initiated grant from Nestle (JPK). Nestle Product Technology Center and Cereal Partners Worldwide provided the study meals and foods.

Ovarian suppression with gonadotropin-releasing hormone agonist reduces whole body protein turnover in women

2006 ◽  
Vol 291 (3) ◽  
pp. E483-E490 ◽  
Author(s):  
Michael J. Toth ◽  
Cynthia K. Sites ◽  
Dwight E. Matthews ◽  
Peter R. Casson
Keyword(s):  
Protein Metabolism ◽  
Protein Turnover ◽  
Gonadotropin Releasing Hormone ◽  
Fat Free Mass ◽  
Whole Body ◽  
Ovarian Hormone ◽  
Protein Breakdown ◽  
Body Protein ◽  
Ovarian Suppression ◽  
Gonadotropin Releasing Hormone Agonist

The age-related decline in fat-free mass is accelerated in women after menopause. The role of ovarian hormone deficiency in the regulation of fat-free mass, however, has not been clearly defined. To address this question, we examined the effect of ovarian hormone suppression on whole body protein metabolism. Whole body protein breakdown, oxidation, and synthesis were measured using [13C]leucine in young, healthy women with regular menstrual patterns before and after 2 mo of treatment with gonadotropin-releasing hormone agonist (GnRHa; n = 6) or placebo ( n = 7). Protein metabolism was measured under postabsorptive and euglycemic-hyperinsulinemic-hyperaminoacidemic conditions. Ovarian suppression did not alter whole body or regional fat-free mass or adiposity. In the postabsorptive state, GnRHa administration was associated with reductions in protein breakdown and synthesis ( P < 0.05), whereas no change in protein oxidation was noted. Under euglycemic-hyperinsulinemic-hyperaminoacidemic conditions, a similar reduction ( P < 0.05) in protein synthesis and breakdown was noted, whereas, protein oxidation increased ( P < 0.05) in the placebo group. Testosterone, steroid hormone precursors, insulin-like growth factor I, and their respective binding proteins were not altered by GnRHa administration, and changes in these hormones over time were not associated with GnRHa-induced alterations in protein metabolism, suggesting that changes in protein turnover are not due to an effect of ovarian suppression on other endocrine systems. Our findings provide evidence that endogenous ovarian hormones participate in the regulation of protein turnover in women.

The Excretion of Isotope in Urea and Ammonia for Estimating Protein Turnover in Man with [15N]Glycine

1981 ◽  
Vol 61 (2) ◽  
pp. 217-228 ◽  
Author(s):  
E. B. Fern ◽  
P. J. Garlick ◽  
Margaret A. McNurlan ◽  
J. C. Waterlow
Keyword(s):  
Protein Metabolism ◽  
Protein Turnover ◽  
Mean Value ◽  
Intravenous Dose ◽  
Whole Body ◽  
Body Protein ◽  
End Products ◽  
The Mean ◽  
15N Urea ◽  
Normal Adults

1. Four normal adults were given [15N]-glycine in a single dose either orally or intravenously. Rates of whole-body protein turnover were estimated from the excretion of 15N in ammonia and in urea during the following 9 h. The rate derived from urea took account of the [15N]urea retained in body water. 2. In postabsorptive subjects the rates of protein synthesis given by ammonia were equal to those from urea, when the isotope was given orally, but lower when an intravenous dose was given. 3. In subjects receiving equal portions of food every 2 h rates of synthesis calculated from ammonia were much lower than those from urea whether an oral or intravenous isotope was given. Comparison of rates obtained during the post-absorptive and absorptive periods indicated regulation by food intake primarily of synthesis when measurements were made on urea, but regulation primarily of breakdown when measurements were made on ammonia. 4. These inconsistencies suggest that changes in protein metabolism might be assessed better by correlating results given by different end-products, and it is suggested that the mean value given by urea and ammonia will be useful for this purpose.

Enhancement of tumor proteolysis by TNF-alpha: correlation of in vivo isotope estimates with growth

1991 ◽  
Vol 261 (1) ◽  
pp. R106-R116
Author(s):  
N. W. Istfan ◽  
P. R. Ling ◽  
G. L. Blackburn ◽  
B. R. Bistrian
Keyword(s):  
Protein Synthesis ◽  
Protein Metabolism ◽  
Whole Body ◽  
Independent Effect ◽  
Yoshida Sarcoma ◽  
Protein Breakdown ◽  
Body Protein ◽  
Breakdown Rates ◽  
Made In

To evaluate the accuracy of in vivo estimates of protein synthesis and breakdown, measurements of plasma and tissue leucine kinetics were made in rat tumor tissues at different conditions of growth by use of constant intravenous infusion of [14C]leucine. These measurements were made in Yoshida sarcoma tumors on days 10 and 13 after implantation, with and without tumor necrosis factor (TNF) infusion and on day 10 in Walker-256 carcinosarcoma. Expressed as micromoles of leucine per gram tissue, tumor protein breakdown increased (P less than 0.01) from 0.32 +/- 0.02 to 0.52 +/- 0.09 (SE) mumol/h, with progress of the Yoshida sarcoma tumor between days 10 and 13 after implantation. Similarly, TNF increased tumor proteolysis on day 10 (0.43 +/- 0.03 mumol.h-1.g-1, P less than 0.05 vs. day 10 control) but not on day 13 after implantation of the Yoshida tumor. Estimates of growth derived from the difference between protein synthesis and breakdown rates were not statistically different from those based on actual tumor volume changes in both tumor models. However, estimates of “whole body” protein metabolism (plasma leucine flux) were not affected either by tumor aging or by treatment with TNF. This study shows that in vivo estimates of tissue protein metabolism based on our [14C]leucine constant infusion model closely reflect the growth characteristic of that tissue. A cytotoxic perfusion-independent effect for intravenous TNF on growing tumor tissue is demonstrable as increased protein breakdown. Furthermore, the commonly used concept of whole body protein metabolism, derived solely from tracer dilution in plasma, is an oversimplification.

Whole Body Protein Metabolism in Human Pulmonary Tuberculosis and Undernutrition: Evidence for Anabolic Block in Tuberculosis

1998 ◽  
Vol 94 (3) ◽  
pp. 321-331 ◽  
Author(s):  
Derek C. MacAllan ◽  
Margaret A. McNurlan ◽  
Anura V. Kurpad ◽  
George De Souza ◽  
Prakash S. Shetty ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Body Mass ◽  
Protein Metabolism ◽  
Protein Turnover ◽  
Nutrition Support ◽  
Whole Body ◽  
Body Protein ◽  
Leucine Kinetics ◽  
Body Energy ◽  
Net Protein

1. Differing patterns of protein metabolism are seen in wasting due to undernutrition and wasting due to chronic infection. 2. We investigated whole body energy and protein metabolism in nine subjects with pulmonary tuberculosis, six undernourished subjects (body mass index < 18.5 kg/m2) and seven control subjects from an Indian population. Fasting subjects were infused with l-[1-13C] leucine (2.3 μmol · h−1 · kg−1) for 8 h, 4 h fasted then 4 h fed. Leucine kinetics were derived from 13C-enrichment of leucine and α-ketoisocaproic acid in plasma and CO2 in breath. 3. Undernourished subjects, but not tuberculosis subjects, had higher rates of whole body protein turnover per unit lean body mass than controls [163.1 ± 9.4 and 148.6 ± 14.6 μmol compared with 142.8 ± 14.7 μmol leucine/h per kg, based on α-ketoisocaproic acid enrichment (P = 0.039)]. 4. In response to feeding, protein oxidation increased in all groups. Tuberculosis subjects had the highest fed rates of oxidation (47.0 ± 10.5 compared with 37.1 ± 5.4 μmol · h−1 · kg−1 in controls), resulting in a less positive net protein balance in the fed phase (controls, 39.7 ± 6.2; undernourished subjects, 29.2 ± 10.6; tuberculosis subjects, 24.5 ± 93; P = 0.010). Thus fed-phase tuberculosis subjects oxidized a greater proportion of leucine flux (33.2%) than either of the other groups (controls, 24.0%; undernourished subjects, 24.0%; P = 0.017). 5. Tuberculosis did not increase fasting whole body protein turnover but impaired the anabolic response to feeding compared with control and undernourished subjects. Such ‘anabolic block’ may contribute to wasting in tuberculosis and may represent the mechanism by which some inflammatory states remain refractory to nutrition support.

Fasting and postprandial phenylalanine and leucine kinetics in liver cirrhosis

1994 ◽  
Vol 267 (1) ◽  
pp. E140-E149 ◽  
Author(s):  
P. Tessari ◽  
S. Inchiostro ◽  
R. Barazzoni ◽  
M. Zanetti ◽  
R. Orlando ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Protein Turnover ◽  
Normal Subjects ◽  
Whole Body ◽  
Protein Breakdown ◽  
Phenylalanine Concentration ◽  
Mixed Meal ◽  
Body Protein ◽  
Plasma Phenylalanine ◽  
Leucine Kinetics

To investigate body protein turnover and the pathogenesis of increased concentration of plasma phenylalanine in liver cirrhosis, we have studied phenylalanine and leucine kinetics in cirrhotic (diabetic and nondiabetic) patients, and in normal subjects, both in the postabsorptive state and during a mixed meal, using combined intravenous and oral isotope infusions. Postabsorptive phenylalanine concentration and whole body rate of appearance (Ra) were approximately 40% greater (P < 0.05) in patients than in controls. Leucine concentrations were comparable, but intracellular leucine Ra was also increased (P < 0.05), suggesting increased whole body protein breakdown. Postprandial phenylalanine Ra was also greater (P < 0.05) in the patients. This difference was due to a diminished fractional splanchnic uptake of the dietary phenylalanine (approximately 40% lower in the cirrhotics vs. controls, P < or = 0.05). Postprandial leucine Ra was also increased in the patients, but splanchnic uptake of dietary leucine was normal. Thus both increased body protein breakdown and decreased splanchnic extraction of dietary phenylalanine can account for the increased phenylalanine concentrations in liver cirrhosis.

Aspects of protein metabolism after elective surgery in patients receiving constant nutritional support

1990 ◽  
Vol 78 (6) ◽  
pp. 621-628 ◽  
Author(s):  
F. Carli ◽  
J. Webster ◽  
V. Ramachandra ◽  
M. Pearson ◽  
M. Read ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Metabolic Rate ◽  
Protein Metabolism ◽  
Protein Turnover ◽  
Resting Metabolic Rate ◽  
Plasma Concentrations ◽  
Whole Body ◽  
Body Protein ◽  
Urinary Nitrogen

1. The present study was designed in an attempt to resolve conflicting views currently in the literature relating to the effect of surgery on various aspects of protein metabolism. 2. Sequential post-operative (2, 4 and 6 days) changes in whole-body protein turnover, forearm arteriovenous difference of plasma amino acids, glucose, lactate and free fatty acids, muscle concentration of free amino acids, RNA and protein, urinary nitrogen and 3-methylhistidine, plasma concentrations of insulin, cortisol and growth hormone, and resting metabolic rate, were measured in six patients undergoing uncomplicated elective total abdominal hysterectomy. 3. All patients received a constant daily diet, either orally or intravenously, based on 0.1 g of nitrogen/kg and an energy content of 1.1 times the resting metabolic rate for 7 days before and 6 days after surgery. 4. Whole-body protein turnover, synthesis and breakdown increased significantly 2 days after surgery (P <0.05) and returned towards pre-operative levels thereafter. 5. Forearm release of branched-chain amino acids and alanine, and efflux of glucose and lactate, were enhanced 4 days after surgery (P <0.05). Muscle glutamine and alanine concentrations were decreased on the fourth and sixth days after surgery (P <0.05). The RNA/protein ratio (indicating the capacity for protein synthesis) was unaltered. 6. A significant increase in urinary nitrogen and 3-methylhistidine was observed on days 3 and 4 after surgery (P <0.05). Thereafter, these parameters remained elevated, although failing to reach statistical significance. 7. The resting metabolic rate was significantly increased (P <0.05) 2 days after surgery but the respiratory quotient (0.77) was unchanged. 8. These data support the contention that whole-body protein synthesis and breakdown increase after surgery. Differences observed pre- and post-operatively between leucine kinetic estimates and other methods of quantifying protein metabolism indicate that only like methodologies should be compared.

Increased bone turnover is associated with protein and energy metabolism in adolescents with sickle cell anemia

2001 ◽  
Vol 280 (3) ◽  
pp. E518-E527 ◽  
Author(s):  
Maciej S. Buchowski ◽  
F. Alexander de la Fuente ◽  
Paul J. Flakoll ◽  
Kong Y. Chen ◽  
Ernest A. Turner
Keyword(s):  
Energy Expenditure ◽  
Bone Turnover ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Protein Turnover ◽  
Type I Collagen ◽  
Whole Body ◽  
Type I ◽  
Protein Breakdown ◽  
Body Protein

Contribution of bone turnover to the hypercatabolic state observed in sickle cell anemia is unknown. We examined the association between markers of bone turnover and basal rates of whole body protein turnover and energy expenditure in 28 adolescents with homozygous sickle cell anemia (HbSS) and in 26 matched controls with normal phenotype (HbAA). Whole body protein breakdown and synthesis were measured using a stable isotope of [15N]glycine, resting energy expenditure was measured by whole room indirect calorimetry, and the rate of pyridinoline cross-link (PYD) excretion in urine and fasting serum levels of the type I procollagen carboxy-terminal propeptide (PICP) were measured with commercial kits. Urinary PYD and serum PICP were significantly elevated in HbSS patients. The increase in procollagen synthesis, indicated by high levels of PICP, was significantly correlated with increased whole body protein synthesis. The increase in type I collagen degradation, indicated by high PYD excretion, was significantly correlated with increased protein breakdown. We conclude that increased rates of bone turnover contribute to the increased rates of protein turnover and energy expenditure observed in adolescents with homozygous sickle cell anemia.

Muscle wasting in emphysema

1988 ◽  
Vol 75 (4) ◽  
pp. 415-420 ◽  
Author(s):  
W. L. Morrison ◽  
J. N. A. Gibson ◽  
C. Scrimgeour ◽  
M. J. Rennie
Keyword(s):  
Protein Synthesis ◽  
Protein Turnover ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Myofibrillar Protein ◽  
Whole Body ◽  
Protein Breakdown ◽  
Body Protein ◽  
Net Protein

1. We have investigated arteriovenous exchanges of tyrosine and 3-methylhistidine across leg tissue in the postabsorptive state as specific indicators of net protein balance and myofibrillar protein breakdown, respectively, in eight patients with emphysema and in 11 healthy controls. Whole-body protein turnover was measured using l-[1-13C]leucine. 2. Leg efflux of tyrosine was increased by 47% in emphysematous patients compared with normal control subjects, but 3-methylhistidine efflux was not significantly altered. 3. In emphysema, whole-body leucine flux was normal, whole-body leucine oxidation was increased, and whole-body protein synthesis was depressed. 4. These results indicate that the predominant mechanism of muscle wasting in emphysema is a fall in muscle protein synthesis, which is accompanied by an overall fall in whole-body protein turnover.

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