Axis In Healthy Men Research Articles

Relationship between meteorological factors and the pituitary-thyroid axis in healthy men living in the Subarctic

BACKGROUND: The changing seasons in the subarctic region causes an adaptive restructuring of the inhabitants’ organisms. The most healthy individuals can adjust to the Northern climate without developing health disorders. However, a decrease in adaptive reserves may result in various pathological conditions. Extensive studies across different populations in various climatic zones have reported significant associations between meteorological factors and the fluctuations in thyroid hormones. AIM: To assess the influence of circannual dynamics of meteorological factors on the serum levels of thyroid hormones and thyroxin-binding globulin (TBG) in men living in subarctic environmental conditions. MATERIAL AND METHODS: An prospective analytical study was conducted in the city of Arkhangelsk (64°32´24.4˝ N). Twenty clinically healthy men comprised the sample. Blood samples were collected every 3 months over a 12-months period. Subjects with any factors affecting the hypothalamic-pituitary-thyroid axis were excluded. Circannual variation in the studied characteristics were analyzed using Wilcoxon signed-rank tests with Bonferroni correction. Associations between hormonal data and climatic data were assessed using Spearman’s correlation coefficients. RESULTS: The thyroid-stimulating hormone reached its peak, while T4 and TBG were at their lowest during the period of minimal daylight hours in December. This coincided with the highest values of relative humidity and atmospheric pressure. Furthermore, T4 and TBG positively correlated with the duration of daylight and outdoor temperature at the day of samples collection, while showing an inverse correlation with atmospheric pressure and average monthly relative humidity. Т3 and T4 inversely correlated with average monthly atmospheric pressure. T3 was positively associated with the duration of daylight. CONCLUSION: The key environmental factors affecting the health people living in Northern regions include are the duration of daylight, outdoor temperature, monthly atmospheric pressure, and relative humidity. It is important to note that the impact of these climatic conditions on human health varies across the regions. Thus, our findings cannot be generalized to other areas..

The chronic alcohol consumption influences the gonadal axis in men: Results from a meta-analysis.

Low testosterone concentrations affect 2-13% of adult males, with a direct association between reduction in testosterone (T) concentrations and cardiovascular events. Lifestyle habits have been linked to visceral fat accumulation and endocrine disorders like secondary hypogonadism. Alcohol intake has also been a topic of debate, with studies showing a detrimental effect on sperm production and underlying mechanisms. This meta-analysis aims to comprehensively evaluate the effect of alcohol consumption on T serum concentrations in adult men. The literature search included only controlled clinical trials comparing men who drink alcohol to men who do not, or who assumed placebo or nonalcoholic beverages. The primary outcome was the comparison of total testosterone serum concentrations between the study and control groups. The publications were examined for publication bias using Egger's test. Twenty-one studies were included in the analysis for a total of 30 trials that examined the effects of alcohol consumption on testosterone level in 10,199 subjects. The meta-analysis showed that alcohol consumption overall is related to significant reduction in circulating concentrations of total testosterone (mean difference [MD]=-4.02; 95% CI -6.30, -1.73), free T (MD=-0.17; 95% CI -0.23, -0.12), sex hormone binding globulin (SHBG) (MD=-1.94; 95% CI -3.37, -0.48), an increase in estradiol (E2) (MD=7.65; 95% CI 1.06, 14.23) and neutral effect on luteinizing hormone (LH) (MD=-0.15; 95% CI -0.36, 0.06), independently by age, body mass index (BMI), E2, and LH serum concentrations and alcohol intake. However, these results are evident only in healthy men exposed to chronic alcohol consumption and not in those with a recognized diagnosis of alcohol use disorder or after acute alcohol intake. This study suggests how chronic alcohol consumption may inhibit the gonadal axis in healthy men, although the exact pathophysiological mechanisms connecting alcohol exposure and steroidogenesis are still not completely clarified.

Functional state of the hypothalamus-pituitary-gonad axis in healthy men with various adaptation potential.

The characterization of the functioning of the blood circulatory system of the organism in terms of its ability to adapt to environmental conditions includes the definition of adaptive potential (AP). The purpose of the study is to supplement the idea of adaptive potential in the aspect of its association with indicators of the hypothalamus-pituitary-gonadal system in healthy men living in the climatic conditions of the Arctic zone of the Russian Federation. The study involved 94 apparently healthy men. Serum hormone levels of the hypothalamus-pituitary-gonadal system were determined by enzyme-linked immunosorbent assay. Percent of men with satisfactory adaptation was 67%. Markers of increased tension in adaptive mechanisms include a decrease in values of testosterone, sex hormone -binding globulin, and testosterone / estradiol ratio. It has been shown that in individuals with a 4-th degree of adaptive potential, the activity of the pituitary-gonadal and the pituitary-adrenal cortex systems participating in the maintenance of the circulatory system is suppressed. That may be associated with a decrease in the reserves of hormone synthesis in these systems. An increase in the tension of the adaptive mechanisms of the circulatory system occurs with a decrease in the levels of anabolic hormones and a simultaneous increase in the level of estradiol as a compensatory reaction to maintain the function of the cardiovascular system. It is established that when moving northward beyond the border of the Arctic Circle an increase in the tension of the adaptive mechanisms of the circulatory system is noted for men living in extreme climatic conditions. The results of the study show a negative correlation of adaptive potential with the values of testosterone, sex hormone-binding globulin and the testosterone / estradiol ratio. The tension of the adaptive mechanisms of the blood circulatory system occurs with decreased sex hormones levels, which can be considered as a marker of disadaptation changes amid the risk of the ecological well-being of the population.

Effects of Glucagon-like Peptide-1 on the Reproductive Axis in Healthy Men.

ContextGlucagon-like peptide-1 (GLP-1) potently reduces food intake and augments glucose-stimulated insulin secretion. Recent animal data suggest that GLP-1 may also influence reproduction. As GLP-1 receptor agonists are currently widely used in clinical practice to treat obesity/type 2 diabetes, it is necessary to determine the effects of GLP-1 on the reproductive system in humans.ObjectiveTo investigate the effects of GLP-1 administration on the reproductive axis in humans.DesignSingle-blind, randomized, placebo-controlled crossover study.SettingClinical Research Facility, Imperial College Healthcare NHS Trust.ParticipantsEighteen healthy men (mean age 24.7 ± 0.1years, mean BMI 22.1 ± 0.4kg/m2).InterventionEight-hour intravenous infusion of 0.8 pmol/kg/min GLP-1 or rate-matched vehicle infusion.Main Outcome MeasuresNumber of luteinizing hormone (LH) pulses, LH, follicle-stimulating hormone (FSH), and testosterone levels.ResultsThe number of LH pulses (number of LH pulses/500 min: vehicle 4.2 ± 0.4, GLP-1 4.5 ± 0.3, P = 0.46), LH area under the curve (AUC) (vehicle 1518 ± 88min.IU/L, GLP-1 1524 ± 101min.IU/L, P = 0.95), follicle-stimulating hormone AUC (vehicle 1210 ± 112 min IU/L, GLP-1 1216 ± 112 min IU/L, P = 0.86), and testosterone AUC (vehicle 10893 ± 615 min nmol/L, GLP-1 11088 ± 792 min nmol/L, P = 0.77) did not significantly differ during vehicle and GLP-1 administration. Glucagon-like peptide-1 significantly reduced food intake (vehicle 15.7 ± 1.3 kcal/kg, GLP-1 13.4 ± 1.3 kcal/kg, P = 0.01).ConclusionsIn contrast to the animal literature, our data demonstrate that acute GLP-1 administration does not affect reproductive hormone secretion in healthy men.

Effects of Peptide YY on the Hypothalamic-Pituitary-Gonadal Axis in Healthy Men.

ContextCentral and peripheral administration of peptide YY (PYY) has potent anorectic effects, and PYY analogs are under development as antiobesity treatments. Recent animal data suggest PYY may also influence the reproductive axis; however the effects of PYY on the human reproductive system are unknown.ObjectiveTo investigate the effects of PYY administration on the reproductive axis in healthy young men.DesignSingle-blind, randomized, placebo-controlled crossover study.SettingClinical Research Facility, Imperial College Healthcare NHS Trust.ParticipantsEighteen healthy eugonadal men (mean age 24.1 ± 0.9 years, mean body mass index 22.2 ± 0.4 kg/m2).InterventionEight-hour intravenous infusion of 0.4 pmol/kg/min PYY3-36 or rate-matched vehicle infusion.Main Outcome MeasuresNumber of luteinizing hormone (LH) pulses, LH, follicle stimulating hormone (FSH), and testosterone levels.ResultsThe number of LH pulses (mean number of LH pulses/8 hours: PYY 4.4 ± 0.3 vs vehicle 4.4 ± 0.4, P > .99), LH area under the curve (AUC) (PYY 1503 ± 79 IU.min/L vs vehicle 1574 ± 86 IU.min/L, P = .36), FSH AUC (PYY 1158 ± 513 IU.min/L vs vehicle 1199 ± 476 IU.min/L, P = .49) and testosterone AUC (PYY 10 485 ± 684 IU.min/L vs vehicle 11 133 ± 803 IU.min/L, P = .24) were similar during PYY and vehicle infusions.ConclusionsAcute intravenous infusion of 0.4 pmol/kg/min PYY does not affect the reproductive axis in healthy men.

SUN-LB044 Effects of Glucagon-Like Peptide-1 (GLP-1) on the Hypothalamic-Pituitary-Gonadal Axis in Healthy Men

Introduction: Normal fertility requires the presence of adequate nutritional stores. The hormone glucagon-like peptide-1 (GLP-1) is a satiety hormone, which is released by intestinal L-cells during meal ingestion to act as a physiological signal of nutritional intake. GLP-1 reduces appetite and stimulates insulin release. Peripheral GLP-1 crosses the blood brain barrier and GLP-1 receptors (GLP-1R) are present in the arcuate nucleus of the hypothalamus (a neuroendocrine centre that regulates metabolism and reproduction). Both in vitro and in vivo animal studies have demonstrated stimulatory effects of GLP-1 on reproductive hormone release. Thus, GLP-1 acts as a signal of adequate energy intake and may act as a key mediator between metabolic and reproductive systems in animals. As GLP-1R agonists are widely used to treat obesity and diabetes, we sought to determine the effects of GLP-1 on the reproductive axis in humans. Methods: Using a blinded placebo-controlled protocol, 18 healthy men (age 24.7±1yr; mean BMI 22.1±0.4kg/m2) received an 8-hour infusion of 0.8pmol/kg/min of GLP-1 on one study visit and rate-matched vehicle infusion on a separate study visit, in random order. Blood samples were taken every ten minutes during infusions. Visual analogue scales (VAS: 0-10cm) for hunger and nausea were completed by the volunteers pre-, mid- and end-infusion. An ad libitum meal study was performed following the last VAS assessment, after which the infusion was stopped. Luteinizing hormone (LH) pulsatility was determined using blinded deconvolution analysis. Data is presented as mean±SEM. Results: GLP-1 infusion resulted in 14% lower food intake (GLP-1 937±87kcal vs vehicle 1094±87kcal, p=0.03) without increasing nausea (change from baseline VAS score: GLP-1 0.25±0.35cm vs vehicle 0.25±0.22cm, p=0.74). There was no difference in the number of LH pulses over 8hrs (GLP-1 4.7±0.3 vs vehicle 4.4±0.4, p=0.38), LH pulse mass (GLP-1 4.82±0.38IU/L vs vehicle 4.78±0.42IU/L, p=0.94), mean LH (GLP-1 2.86±0.2IU/L vs vehicle 2.75±0.2IU/L, p=0.50), LH AUC (GLP-1 1524±101IU.min/L vs vehicle 1484±88IU.min/L, p=0.70), FSH AUC (GLP-1 1216±112IU.min/L vs vehicle 1210±112IU.min/L, p=0.86) or testosterone AUC (GLP-1 11088±792nmol.min/L vs vehicle 10893±615nmol.min/L, p=0.77). Conclusions: Our results indicate that GLP-1 administration, at a biologically active dose (which reduces food intake), has neither a detrimental nor stimulatory effect on the reproductive axis. This provides important safety data for GLP-1 based therapeutic agents. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Provocative stimulation of the hypothalamic-pituitary-testicular axis in men with spinal cord injury.

Prospective study. To determine the integrity of the hypothalamic-pituitary-testicular axis in healthy men with spinal cord injury (SCI). Thirty healthy men with chronic SCI (37±10 years) and thirty-eight able-bodied (AB) controls (36±10 years) participated. Gonadotropin-releasing hormone (GnRH; 100 μg IV) was administered to determine gonadotropin release, and human chorionic gonadotropin (hCG; 4000 IU IM) was administered to determine testosterone (T) secretion. Responses to stimulation were categorized as 'responder' or 'non-responder' by clinical criteria. Single factor ANOVA with repeated measures was performed to identify group differences. The proportion of responders to pituitary GnRH stimulation was similar in the SCI group (22 subjects (73%) for the follicular-stimulating hormone (FSH) and 23 subjects (76%) for the luteinizing hormone (LH) to that of the AB group. The SCI-responder group had an increased FSH response after stimulation compared with the AB-responder group (P<0.05). The SCI-responder group had a greater LH area under the curve to GnRH stimulation than the AB-responder group (P=0.06). The peak FSH response was at 60 min and the peak LH response at 30 min, regardless of group designation. All groups had similar increases in serum T concentration to hCG stimulation. The pituitary response to stimulation in healthy men with SCI revealed an augmented FSH response; LH response only trended higher. The testicular response to provocative stimulation was similar in hypogonadal and eugondal subjects and in GnRH responders and non-responders. These findings suggest a lack of hypothalamic drive of pituitary gonadotropin release in healthy people with chronic SCI.

Adverse effects of two nights of sleep restriction on the hypothalamic-pituitary-adrenal axis in healthy men.

Insufficient sleep is associated with increased cardiometabolic risk. Alterations in hypothalamic-pituitary-adrenal axis may underlie this link. Our objective was to examine the impact of restricted sleep on daytime profiles of ACTH and cortisol concentrations. Thirteen subjects participated in 2 laboratory sessions (2 nights of 10 hours in bed versus 2 nights of 4 hours in bed) in a randomized crossover design. Sleep was polygraphically recorded. After the second night of each session, blood was sampled at 20-minute intervals from 9:00 am to midnight to measure ACTH and total cortisol. Saliva was collected every 20 minutes from 2:00 pm to midnight to measure free cortisol. Perceived stress, hunger, and appetite were assessed at hourly intervals by validated scales. Sleep restriction was associated with a 19% increase in overall ACTH levels (P < .03) that was correlated with the individual amount of sleep loss (rSp = 0.63, P < .02). Overall total cortisol levels were also elevated (+21%; P = .10). Pulse frequency was unchanged for both ACTH and cortisol. Morning levels of ACTH were higher after sleep restriction (P < .04) without concomitant elevation of cortisol. In contrast, evening ACTH levels were unchanged while total and free cortisol increased by, respectively, 30% (P < .03) and 200% (P < .04). Thus, the amplitude of the circadian cortisol decline was dampened by sleep restriction (-21%; P < .05). Sleep restriction was not associated with higher perceived stress but resulted in an increase in appetite that was correlated with the increase in total cortisol. The impact of sleep loss on hypothalamic-pituitary-adrenal activity is dependent on time of day. Insufficient sleep dampens the circadian rhythm of cortisol, a major internal synchronizer of central and peripheral clocks.

Partial sleep restriction modulates secretory activity of thyrotropic axis in healthy men

Sleep and endocrine function are known to be closely related, but studies on the effect of moderate sleep loss on endocrine axes are still sparse. We examined the influence of partial sleep restriction for 2days on the secretory activity of the thyrotropic axis. Fifteen healthy, normal-weight men were tested in a balanced, cross-over study. Serum concentrations of thyrotrophin (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) were monitored at 1-h intervals during a 15-h daytime period (08:00-23:00h) following two nights of restricted sleep (bedtime 02:45-07:00h) and two nights of regular sleep (bedtime 22:45-07:00h), respectively. Serum concentrations of fT3 (P<0.026) and fT4 (P=0.089) were higher after sleep restriction than regular sleep, with a subsequent blunting of TSH concentrations in the evening hours of the sleep restriction condition (P=0.008). These results indicate profound alterations in the secretory activity of the thyrotropic axis after 2days of sleep restriction to ~4h, suggesting that acute partial sleep loss impacts endocrine homeostasis, with potential consequences for health and wellbeing.

A friendly version of the Trier Social Stress Test does not activate the HPA axis in healthy men and women

The Trier Social Stress Test (TSST) is a well-established laboratory stressor leading to a robust activation of the hypothalamus–pituitary–adrenal (HPA) axis. Existing control conditions are often not adequate to investigate participants' behavior during the situation as participants are often left alone in the room. This present study aimed to evaluate a friendly version of the TSST as control condition, the friendly-TSST (f-TSST). We expected that the f-TSST would not activate the HPA axis or increase the negative affect (NA). Forty-eight healthy male and female students (24 males) aged between 18 and 30 years were randomly exposed to either the TSST or the f-TSST. The latter features a similar structure and similar cognitive demands as in the TSST, and a social interaction with a committee. The main difference lies in the friendly and warm behavior of the committee opposed to the neutral and reserved behavior in the TSST, typically inducing social-evaluative threat. Salivary cortisol, salivary α-amylase (sAA), and affect were measured to evaluate the stress response to the respective procedure. As expected, the f-TSST neither activated the HPA axis nor increased the NA. The TSST by contrast led to an increase in both measures. A comparable and significant increase in the sAA-concentrations occurred in both conditions. The f-TSST could be useful as a standardized control condition for future stress studies. On a conceptual level our data indicate that mere social performance in the absence of social-evaluative threat and performance pressure does not activate the HPA axis.

Age disrupts androgen receptor-modulated negative feedback in the gonadal axis in healthy men

Testosterone (T) exerts negative feedback on the hypothalamo-pituitary (GnRH-LH) unit, but the relative roles of the CNS and pituitary are not established. We postulated that relatively greater LH responses to flutamide (brain-permeant antiandrogen) than bicalutamide (brain-impermeant antiandrogen) should reflect greater feedback via CNS than pituitary/peripheral androgen receptor-dependent pathways. To this end, 24 healthy men ages 20-73 yr, BMI 21-32 kg/m2, participated in a prospective, placebo-controlled, randomized, double-blind crossover study of the effects of antiandrogen control of pulsatile, basal, and entropic (pattern regularity) measurements of LH secretion. Analysis of covariance revealed that flutamide but not bicalutamide 1) increased pulsatile LH secretion (P = 0.003), 2) potentiated the age-related abbreviation of LH secretory bursts (P = 0.025), 3) suppressed incremental GnRH-induced LH release (P = 0.015), and 4) decreased the regularity of GnRH-stimulated LH release (P = 0.012). Furthermore, the effect of flutamide exceeded that of bicalutamide in 1) raising mean LH (P = 0.002) and T (P = 0.017) concentrations, 2) accelerating LH pulse frequency (P = 0.013), 3) amplifying total (basal plus pulsatile) LH (P = 0.002) and T (P < 0.001) secretion, 4) shortening LH secretory bursts (P = 0.032), and 5) reducing LH secretory regularity (P < 0.001). Both flutamide and bicalutamide elevated basal (nonpulsatile) LH secretion (P < 0.001). These data suggest the hypothesis that topographically selective androgen receptor pathways mediate brain-predominant and pituitary-dependent feedback mechanisms in healthy men.

Ghrelin and the enteroinsular axis in healthy men

Ghrelin, a potent stimulator of GH secretion, also acts as an orexigenic hormone. Plasma ghrelin levels rise before meals with postprandial reduction, suggesting that circulating levels of enteroinsular hormones might influence ghrelin secretion. The aim of this study was to evaluate the effects of ghrelin on enteroinsular hormones in healthy men. Three tests were performed on 3 different days in 6 healthy men: On the first day, saline was infused from 0-120 minutes followed by a ghrelin bolus (1 microg/kg) administration (Test 1); on the second experimental day, GHRH was administered at 0 min, and a ghrelin bolus was given at 120 min (Test 2); on the third experimental day, GHRP-6 was administered at 0 min, followed by a ghrelin bolus at 120 min (Test 3). Plasma glucose, insulin, proinsulin, C-Peptide Glucagone Like Peptide one (GLP-1) determined at 0, 15, 30, 60, 90, and 120 min of the test period. There was a significant increase in AUC glucose (526.41+/-22.91 mmol . ml(-1) . min vs. 566.37+/-15.64 mmol . ml(-1) . min; p<0.05) and AUC insulin (756.25+/-107.56 mU . ml(-1) . min vs. 981.62+/-180.32 mU . ml(-1) . min; p<0.05) and a significant decrease in AUC GLP-1 (2346.87+/-874.28 pmol . ml(-1) . min vs. 1769.5+/-784 pmol . ml(-1) . min; p<0.05) after ghrelin administration in Test 1 compared to Test 3. There was a mild but non-significant increase in AUC for insulin, proinsulin, and C-Peptide and a mild reduction in AUC GLP-1 after every ghrelin administration. There was no evidence of a direct effect of ghrelin administration on enteroinsular hormone levels in this study. However, ghrelin may potentiate the glucose-insulin stimulatory effects of GHRP-6. More studies should be carried out for further evaluation of ghrelin-enteroinsular hormones interplay.

The pituitary-thyroid axis in healthy men living under subarctic climatological conditions.

In order to evaluate the effects of climatic factors on the secretion of thyroid hormones and TSH in a high latitude population, we have taken serum and urine samples from 20 healthy men from northern Finland (67 degrees -68 degrees N) every 2 months for a period of 14 months. Serum free triiodothyronine (T(3)) levels were lower in February than in August (3.9 vs 4.4 pmol/l, P<0.05) and TSH levels were higher in December than during other months (2.1 vs 1.5-1.7 mU/l, P<0.01). Serum total and free thyroxine (T(4)), total T(3) and reverse T(3) levels and urinary T(4) levels were unchanged. Urinary T(3) levels were significantly higher in winter than in summer. Serum free T(3) correlated highly significantly with the outdoor temperature integrated backwards weekly for 7-56 days (r=0.26 for 1-56 days) from the day when the blood samples were taken. Serum TSH did not show any significant correlation with the thyroid hormones or with the integrated temperature of the previous days, but it did show an inverse and significant correlation (r=-0.31) with the ambient luminosity integrated backwards for 7 days from the day when the blood sample was taken. The gradually increasing correlation between outdoor temperatures and serum free T(3) suggests that the disposal of thyroid hormones is accelerated in winter, leading to low serum free T(3) levels and a high urinary free T(3) excretion. Since there was no correlation between thyroid hormones and serum TSH, the feedback mechanism between TSH and thyroid hormones may not be the only contributing factor, and other factors such as ambient luminosity may at least partly determine serum TSH in these conditions. Also urinary free T(3) appears to be a novel and non-invasive indicator for thyroid physiology.

Effects of tumor necrosis factor on the hypothalamic-pituitary-testicular axis in healthy men

Tumor necrosis factor (TNF) has been implicated as a mediator of many diseases associated with alterations in hypothalamic-pituitary-testicular (HPT) function. To assess the effects of TNF on the HPT axis, we performed a saline-controlled cross-over study in six healthy men, sequentially measuring serum concentrations of gonadotropins, testosterone, and sex hormone-binding globulin (SHBG) after a bolus intravenous injection of recombinant human TNF (50 μg/m 2). TNF induced an early and transient increase inserum luteinizing hormone (LH) levels from 6.0 ± 1.0 to a maximum of 8.0 ± 1.0 U/L after 30 minutes ( P < .005), whereas the concentrations of follicle-stimulating hormone (FSH) remained unchanged. The increase in LH concentrations was followed by a transient decrease in serum testosterone levels from 18.2 ± 0.3 to 9.1 ± 1.2 nmol/L after 4 hours ( P < .0001). Remarkably, LH levels had returned to control values when the testosterone level reached its nadir. SHBG levels were not affected by TNF. Our results suggest that TNF affects the HPT axis at multiple levels and may be involved either directly or indirectly in the decrease in circulating testosterone concentrations in systemic illnesses.

Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men

The effect of chronic administration of phosphatidylserine derived from brain cortex on the neuroendocrine responses to physical stress has been examined in a placebo-controlled study in 9 healthy men. Phosphatidylserine 800 mg/d for 10 days significantly blunted the ACTH and cortisol responses to physical exercise (P = 0.003 and P = 0.03, respectively), without affecting the rise in plasma GH and PRL. Physical exercise significantly increased the plasma lactate concentration both after placebo and phosphatidylserine. The results suggest that chronic oral administration of phosphatidylserine may counteract stress-induced activation of the hypothalamo-pituitary-adrenal axis in man.