Protein supplementation does not alter intramuscular anabolic signaling or endocrine response after resistance exercise in trained men.

The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway appears to be the primary regulator of muscle protein synthesis. A variety of stimuli including resistance exercise, amino acids, and hormonal signals activate mTORC1 signaling. The purpose of this study was to investigate the effect of a protein supplement on mTORC1 signaling following a resistance exercise protocol designed to promote elevations in circulating hormone concentrations. We hypothesized that the protein supplement would augment the intramuscular anabolic signaling response. Ten resistance-trained men (age, 24.7 ± 3.4 years; weight, 90.1 ± 11.3 kg; height, 176.0 ± 4.9 cm) received either a placebo or a supplement containing 20 g protein, 6 g carbohydrates, and 1 g fat after high-volume, short-rest lower-body resistance exercise. Blood samples were obtained at baseline, immediately, 30 minutes, 1 hour, 2 hours, and 5 hours after exercise. Fine-needle muscle biopsies were completed at baseline, 1 hour, and 5 hours after exercise. Myoglobin, lactate dehydrogenase, and lactate concentrations were significantly elevated after resistance exercise (P < .0001); however, no differences were observed between trials. Resistance exercise also elicited a significant insulin, growth hormone, and cortisol response (P < .01); however, no differences were observed between trials for insulin-like growth factor-1, insulin, testosterone, growth hormone, or cortisol. Intramuscular anabolic signaling analysis revealed significant elevations in RPS6 phosphorylation after resistance exercise (P = .001); however, no differences were observed between trials for signaling proteins including Akt, mTOR, p70S6k, and RPS6. The endocrine response and phosphorylation status of signaling proteins within the mTORC1 pathway did not appear to be altered by ingestion of supplement after resistance exercise in resistance-trained men.

Dietary arginine and linear growth: the Copenhagen School Child Intervention Study.

The amino acid arginine is a well-known growth hormone (GH) stimulator and GH is an important modulator of linear growth. The aim of the present study was to investigate the effect of dietary arginine on growth velocity in children between 7 and 13 years of age. Data from the Copenhagen School Child Intervention Study during 2001-2 (baseline), and at 3-year and 7-year follow-up, were used. Arginine intake was estimated via a 7 d precoded food diary at baseline and 3-year follow-up. Data were analysed in a multilevel structure in which children were embedded within schools. Random intercept and slopes were defined to estimate the association between arginine intake and growth velocity, including the following covariates: sex; age; baseline height; energy intake; puberty stage at 7-year follow-up and intervention/control group. The association between arginine intake and growth velocity was significant for the third and fourth quintile of arginine intake (2.5-2.8 and 2.8-3.2 g/d, respectively) compared with the first quintile ( < 2.2 g/d) (P for trend = 0.04). Protein intake (excluding arginine) was significantly associated with growth velocity; however, the association was weaker than the association between arginine intake and growth velocity (P for trend = 0.14). The results of the present study suggest a dose-dependent physiological role of habitual protein intake, and specifically arginine intake, on linear growth in normally growing children. However, since the study was designed in healthy children, we cannot firmly conclude whether arginine supplementation represents a relevant clinical strategy. Further research is needed to investigate whether dietary arginine may represent a nutritional strategy potentially advantageous for the prevention and treatment of short stature.

GABA supplementation and growth hormone response.

The secretion of growth hormone (GH) is regulated through a complex neuroendocrine control system, especially by the functional interplay of two hypothalamic hormones, GH-releasing hormone and somatostatin. These hormones are subject to modulation by a host of neurotransmitters and are the final mediators of endocrine and neural influences for GH secretion. Interest in the possible role of γ-aminobutyric acid (GABA) in the control of GH secretion began decades ago. However, interest in its role as an ergogenic aid is only recent. It is well accepted that GABAergic neurons are found in the hypothalamus and recent evidence suggests its secretion within the pituitary itself. Inhibition of GABA degradation and blockade of GABA transmission as well as administration of GABA and GABA mimetic drugs have all been shown to affect GH secretion. However, there are many controversial findings. The effects may depend on the site of action within the hypothalamic-pituitary unit and the hormonal milieu. Experimental and clinical evidence support the presence of a dual action of GABA - one mediated centrally, the other exerted directly at the pituitary level. The two sites of action may be responsible for excitatory and inhibitory effects of GABA on GH secretion. This chapter will outline the anatomical basis for possible influences of GABA on GH secretion and present evidence for a role of GABA in the control of GH release by actions at either hypothalamic or pituitary sites. The potential ergogenic benefits of oral GABA supplementation will also be discussed.

An examination of the effects of the antioxidant Pycnogenol on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population.

The study examines the effects of the antioxidant flavonoid Pycnogenol on a range of cognitive and biochemical measures in healthy elderly individuals. The study used a double-blind, placebo-controlled, matched-pair design, with 101 elderly participants (60-85 years) consuming a daily dose of 150 mg of Pycnogenol for a three-month treatment period. Participants were assessed at baseline, then at 1, 2, and 3 months of the treatment. The control (placebo) and Pycnogenol groups were matched by age, sex, body mass index, micronutrient intake, and intelligence. The cognitive tasks comprised measures of attention, working memory, episodic memory, and psychomotor performance. The biological measures comprised levels of clinical hepatic enzymes, serum lipid profile, human growth hormone, and lipid peroxidation products. Statistically significant interactions were found for memory-based cognitive variables and lipid peroxidation products, with the Pycnogenol group displaying improved working memory and decreased concentrations of F2-isoprostanes relative to the control group.

Growth hormone, arginine and exercise.

PURPOSE OF REVIEW: To describe the effect of an acute bout of exercise on growth hormone responses and to discuss the effect of L-arginine supplementation on growth hormone responses. RECENT FINDINGS: Recent studies have shown that resting growth hormone responses increase with oral ingestion of L-arginine and the dose range is 5-9 g of arginine. Within this range there is a dose-dependent increase and higher doses are not well tolerated. Most studies using oral arginine have shown that arginine alone increases the resting growth hormone levels at least 100%, while exercise can increase growth hormone levels by 300-500%. The combination of oral arginine plus exercise attenuates the growth hormone response, however, and only increases growth hormone levels by around 200% compared to resting levels. SUMMARY: Exercise is a very potent stimulator of growth hormone release and there is considerable research documenting the dramatic growth hormone rise. At rest oral L-arginine ingestion will enhance the growth hormone response and the combination of arginine plus exercise increases growth hormone, but this increase may be less than seen with exercise alone. This diminished response is seen in both in both younger and older individuals.

[Effect of L-arginine supplementation on secretion of human growth hormone and insulin-like growth factor in adults]. / Efeito da suplementação de L-arginina sobre a secreção de hormônio do crescimento e fator de crescimento semelhante à insulina em adultos.

Based on presumptions that the infusion of amino acids can augment the release of human growth hormone (hGH) and that this metabolism is related with secretion of insulin-like growth factor I (IGF-I), the purpose of this study was to verify the effect of L-arginine supplementation on GH and IGF-I in adults. Seventeen male individuals participated on the study and were randomized to receive L-arginine (n= 10) or placebo (n= 7), seven grams per day for seven days. Before and after the supplementation period, the volunteers realized blood collection in fasting to verify both GH and IGF-I levels, as well as urine collection to verify urea excretion. At the end of the experimental period, it was verified that the group that received L-arginine augmented the urea in urine excretion (to 2684.1 +/- 475.2 mg/dl from 2967.2 +/- 409.7 mg/dl, p= 0.002), therefore it did not alter significantly the release of hormones evaluated. The group which received placebo did not alter significantly any evaluated parameters. The L-arginine supplementation during seven days was ineffective to augment both GH and IGF-I release in individual male adults.

Efeito da suplementação de L-arginina sobre a secreção de hormônio do crescimento e fator de crescimento semelhante à insulina em adultos / Effect of L-arginine supplementation on secretion of human growth hormone and insuline-like growth factor in adults

Baseado nos pressupostos de que a infusão de aminoácidos pode aumentar a secreção de hormônio de crescimento (GH), e que o metabolismo deste hormônio está relacionado com a secreção do fator de crescimento semelhante à insulina (IGF-I), o objetivo deste estudo foi verificar o efeito da suplementação de L-arginina sobre o GH e IGF-I em adultos. Participaram do estudo 17 indivíduos do sexo masculino, que foram randomizados para receber L-arginina (n= 10) ou placebo (n= 7), sete gramas ao dia, durante um período de sete dias. Antes e após o período de suplementação, os voluntários realizaram coleta de sangue em jejum para verificação dos níveis séricos de GH e IGF-I, bem como coleta de urina para verificação da excreção de uréia. Ao final do período experimental, verificamos que o grupo que recebeu L-arginina aumentou a excreção de uréia na urina (de 2684,1 ± 475,2 mg/dl para 2967,2 ± 409,7 mg/dl, p= 0,002), entretanto não modificou significativamente a secreção dos hormônios avaliados. O grupo que recebeu placebo não alterou significativamente nenhum parâmetro avaliado. A suplementação de L-arginina durante sete dias mostrou-se ineficaz para aumentar a secreção de GH e IGF-I em indivíduos adultos do sexo masculino.

Based on presumptions that the infusion of amino acids can augment the release of human growth hormone (hGH) and that this metabolism is related with secretion of insulin-like growth factor I (IGF-I), the purpose of this study was to verify the effect of L-arginine supplementation on GH and IGF-I in adults. Seventeen male individuals participated on the study and were randomized to receive L-arginine (n= 10) or placebo (n= 7), seven grams per day for seven days. Before and after the supplementation period, the volunteers realized blood collection in fasting to verify both GH and IGF-I levels, as well as urine collection to verify urea excretion. At the end of the experimental period, it was verified that the group that received L-arginine augmented the urea in urine excretion (to 2684.1 ± 475.2 mg/dl from 2967.2 ± 409.7 mg/dl, p= 0.002), therefore it did not alter significantly the release of hormones evaluated. The group which received placebo did not alter significantly any evaluated parameters. The L-arginine supplementation during seven days was ineffective to augment both GH and IGF-I release in individual male adults.

In vitro and in vivo trans-esterification of 1-[2(R)-(2-amino-2-methylpropionylamino)-3-(1H-indol-3-yl)propionyl]-3(S)-benzyl-piperidine-3-carboxylic acid ethyl ester and the effects of ethanol on its pharmacokinetics in rats.

PURPOSE: To investigate the in vitro trans-esterification of 1-[2(R)-(2-amino-2-methylpropionylamino)-3-(1H-indol-3-yl)propionyl]-3(S)-benzyl-piperidine-3-carboxylic acid ethyl ester (compound A) and to determine the effects of ethanol on its in vivo pharmacokinetics in male Sprague-Dawley rats. METHODS: The effects of deuterated [d5]ethanol on the hydrolysis and trans-esterification of compound A in rat plasma and rat liver microsomes in the presence or absence of bis(p-nitrophenyl) phosphate (BNPP), a carboxylesterase inhibitor, were investigated. Following an oral pretreatment with deuterated ethanol in conjunction with an intravenous dose of compound A to rats, the pharmacokinetics of compound A and deuterated compound A were evaluated. RESULTS: It was observed that the amount of deuterated compound A generated increased with increasing amounts of deuterated ethanol in incubates, whereas the amount of hydrolyzed product (compound B) decreased. BNPP inhibited both the hydrolysis and the trans-esterification of compound A. Furthermore, the pharmacokinetics of compound A in rats receiving ethanol was altered, such that the plasma clearance decreased by 1.5-fold and the elimination rate constant decreased by 2-fold. Deuterated compound A was determined, confirming that trans-esterification proceeded in vivo; approximately one third of the intravenous dose of compound A underwent trans-esterification. CONCLUSIONS: In the presence of ethanol, compound A underwent trans-esterification catalyzed by carboxylesterases. Ethanol pretreatment resulted in a decrease in the in vivo clearance of compound A mainly due to trans-esterification with ethanol.

Oral arginine does not stimulate basal or augment exercise-induced GH secretion in either young or old adults.

BACKGROUND: Growth hormone (GH) helps maintain body composition and metabolism in adults. However, basal and peak GH decline with age. Exercise produces a physiologic GH response that is subnormal in elderly people. Arginine (Arg) infusion can augment GH secretion, but the efficacy of oral Arg to improve GH response to exercise has not been explored. We investigated whether oral Arg increases GH secretion in young and old people at rest and during exercise. METHODS: Twenty young (Y: 22.1 +/- 0.9 y; SEM) and 8 old (O: 68.5 +/- 2.1 y) male and female subjects underwent three different trials following determination of their one-repetition maximum strength (1-RM); exercise only (EO; 3 sets, 8-10 reps at 85% of 1-RM; on 12 separate resistive lifts), Arg only (5.0 g), or Arg + exercise. Blood samples were collected between successive lifts, and GH (ng x ml(-1)) was determined via RIA. RESULTS: In Y vs O: Basal GH secreted (area under the curve) was 543.6 +/- 84.0 vs 211.5 +/- 63.0. During EO, values were 986.6 +/- 156.6 and 517.8 +/- 85.5. Both were significantly lower in the older individuals (p < .05). Oral Arg alone did not result in any increase in GH secretion at rest (310.8 +/- 73.2 vs 262.9 +/- 141.2). When Arg was coadministered during exercise, GH release was not affected in either the young or old and appeared to be blunted in the young compared to the exercise only trial in the young. CONCLUSION: Based upon these findings, we concluded that oral Arg does not stimulate GH secretion and may impair GH release during resistive exercise.

Neuroendocrine effect of a short-term treatment with DHEA in postmenopausal women.

OBJECTIVES: A progressive decline of plasma dehydroepiandrosterone (DHEA) levels occurs in women during aging related to the reduction of adrenocortical secretion. A specific action of DHEA on the central nervous system (CNS) is suggested by the improvement of psychological and physical well-being in postmenopausal women after DHEA supplementation. The aim of the present study was to investigate the neuroendocrine effects of short-term DHEA supplementation in postmenopausal women, evaluating changes of plasma beta-endorphin (beta-EP) and growth hormone (GH) before and after oral DHEA (100 mg/day) for 7 days in postmenopausal women (n = 6). METHODS: Before and after 7 days of DHEA supplementation, postmenopausal women underwent a neuroendocrine test with clonidine, an alpha 2 presinaptic agonist for adrenergic system (1.25 mg i.v.). Basal plasma DHEA, androstenedione (A), testosterone (T), estrone (E1) and estradiol (E2) levels were evaluated before and after treatment, while plasma beta-EP and GH levels were measured before and 15, 30, 45, 60 and 90 min after clonidine injection. RESULTS: Basal plasma beta-EP and GH levels did not show a significant difference before and after short-term DHEA administration, while circulating A, T, E1 and E2 significantly increased after treatment. The clonidine test induced a significant increase of plasma beta-EP levels in women after receiving DHEA supplementation but not before; conversely, plasma GM levels increased both before and after treatment. CONCLUSIONS: The present study indicates that short-term DHEA supplementation in postmenopausal women is able to restore the impaired response of pituitary beta-EP to clonidine, an alpha 2 presinaptic agonist. According to these data it is possible to hypothesize that DHEA could play a role in the psychological and physical well-being of postmenopausal women acting via a restoration of neuroendocrine control of antero-pituitary beta-EP secretion.

Modulatory effects of a synthetic steroid (tibolone) and estradiol on spontaneous and GH-RH-induced GH secretion in postmenopausal women.

OBJECTIVE: Since hormonal replacement therapy (HRT) affects plasma GH levels, the present study aimed to verify the effect of tibolone, a synthetic steroid, on modulating spontaneous and growth hormone releasing hormone (GH-RH) induced GH secretion. METHODS: Postmenopausal women (n = 30) were enrolled and randomly subdivided in three groups (n = 10 each group): (1) treated with transdermal estradiol (50 micrograms) (Dermestrill, Rottapharm, Monza, Italy) biweekly; (2) treated with transdermal estradiol (100 micrograms) (Dermestrill, Rottapharm, Monza, Italy) biweekly; (3) treated with tibolone 2.5 mg/day (Livial, Organon Italia, Rome, Italy). Patients underwent a GH-RH test (1 microgram/kg) and 15 of them underwent to a pulsatility study before and 5 weeks after treatment. RESULTS: Mean (+ S.E.M.) GH plasma levels increased in all patients after any type of HRT. GH response to GH-RH stimulation (expressed as maximal response to GH-RH or as delta value) was similar in the three groups while significant changes occurred in spontaneous pulsatile GH release. Tibolone and both dosages of transdermal estradiol significantly reduced GH pulse frequency and increased pulse amplitude. CONCLUSIONS: The reduced plasma GH levels observed during postmenopause are probably related to a reduced endogenous GH-RH and not to a reduced pituitary ability to respond to GH-RH. In addition tibolone, as well as transdermal estradiol, are effective in restoring the spontaneous GH episodic release.

Growth hormone secretagogues: focus on the growth hormone-releasing peptides.

This review systematically analyses recent knowledge of the biology of the growth hormone-releasing peptides. Many years before native GHRH had been isolated and sequenced, the synthesis of an enkephalin analog, devoid of any opioid activity but capable of specifically releasing GH from in vitro pituitaries, prompted the design of a number of structurally interrelated GHRPs with improved GH-releasing activity. Nowadays, GHRPs are the most effective GH-secretagogues known and could be used profitably in humans with GH hyposecretory disturbances to promote a pattern of GH secretion that mimics physiology in a better way than the exogenously administered GH.