Altered diurnal pattern of steroid hormones in relation to various behaviors, external factors and pathologies: A review.

The adrenal and gonadal stress steroids [i.e., cortisol, testosterone and dehydroepiandrosterone (DHEA)] have gathered considerable attention in the last few decades due to their very broad physiological and psychological actions. Their diurnal patterns have become a particular focus following new data implicating altered diurnal hormone patterns in various endocrine, behavioral and cardiovascular risk profiles. In this review of the current literature, we present a brief overview of the altered diurnal patterns of these hormones that may occur in relation to chronic stress, nutritional behaviors, physical exercise, drugs and sleep deprivation/shift. We also present data on the altered diurnal hormone patterns implicated in cardiometabolic and psychiatric/neurologic diseases, cancer and other complex pathologies. We consider the occasionally discrepant results of the studies, and summarize the current knowledge in this new field of interest, underlining the potential effects on both biological and psychological functioning, and assess the implications of these effects. Last, we conclude with some practical considerations and perspectives.

Oral contraceptive use and saliva diurnal pattern of metabolic steroid hormones in young healthy women.

BACKGROUND: The impact of oral contraceptives (OCs) on the saliva diurnal pattern of metabolic steroid hormones remained unknown. STUDY DESIGN: Saliva samples were taken from young healthy women (11 OC users, 10 non-OC users) to analyze cortisol, dehydroepiandrosterone (DHEA) and testosterone 4 times (days 1, 8, 15 and 22) over one menstrual cycle. RESULTS: OC use decreased saliva testosterone concentrations (p<.01) under all conditions of day and time, but not saliva cortisol. OC also decreased saliva DHEA concentrations during the first part of the day (p<.05), with a dampened amplitude in its diurnal pattern. CONCLUSION: The clinical relevance requires further study.

Characterization of SM201, an anti-hFcγRIIB antibody not interfering with ligand binding that mediates immune complex dependent inhibition of B cells.

The monoclonal antibody SM201 specifically recognizes the human inhibitory FcγRIIB without showing cross-reactivity to the related but activating FcγRIIA. The epitope recognized by SM201 is located outside the IgG-binding site of FcγRIIB. As a result, the antibody does not interfere with hIgG binding to the receptor. It was therefore hypothesized that SM201 may amplify the inhibitory signaling of FcγRIIB after coligation of B cell receptor (BCR) and FcγRIIB by immune complexes (ICs). Mechanistic and functional studies were conducted in established B cell lines as well as in primary B cells from healthy donors to substantiate the anticipated working principle. Using an experimental setup mimicking IC binding, we were able to demonstrate that SM201 enhances the extent of ITIM phosphorylation of FcγRIIB. The antibody works synergistically with ICs and the mode of action is strictly dependent on their presence. Additionally, SM201 did not induce apoptosis, cellular depletion or NK cell activation, which indicates an advantageous safety profile. This establishes an innovative approach for the treatment of antibody-mediated autoimmune diseases.

Short-term glucocorticoid intake and metabolic responses during long-lasting exercise.

The aim of the study was to evaluate the effects of short-term glucocorticoid treatment on plasma amino acids, free fatty acids, blood glucose, and several hormones in healthy volunteers performing long-lasting exercise. 9 young female subjects exercised 2 h at 50-55% VO2 max twice, once after placebo (Pla) ingestion and once after prednisone (Cor, 50 mg/day/7 days) ingestion, according to a double-blind and randomized protocol. Blood samples were tat rest and during exercise for measurement of amino acids, free fatty acids, blood glucose, adrenocorticotrophic hormone (ACTH), growth hormone, dehydroepiandrosterone (DHEA), insulin, and glucagon. Both ACTH and DHEA values were significantly decreased by Cor vs. Pla (p < 0.01) throughout exercise, and Cor intake also induced lower growth hormone concentrations vs. Pla (p < 0.05) from 60 min to the end of exercise. No significant difference in glucagon, insulin or free fatty acid values was found between the treatments. Branched-chain amino acids and other essential amino acids were significantly higher after Cor vs. Pla from 60 min to the end of exercise (p < 0.05), whereas blood glucose was significantly higher from 90 min to the end of exercise (p < 0.05). We conclude that short-term glucocorticoid intake induces marked hormonal and metabolic changes during long-lasting exercise. Proteolysis can increase with glucocorticoid during this type of exercise and the related higher plasma amino acid concentrations may contribute as energy substrates. Further studies will be necessary to explore and accurately quantify the mechanisms of proteolysis and glyconeogenesis induced by short-term glucocorticoid intake during this type of exercise.

Effects of short-term corticoid ingestion on food intake and adipokines in healthy recreationally trained men.

In order to test the hypothesis that short-term corticoid intake alters food intake, body composition and adipokines secretion in healthy volunteers with regular sport practice, nutrient intake was assessed in eight male athletes with and without prednisolone (PRED, 60 mg/day for 1 week) ingestion in a random, double blind, crossover design. Body weight, body composition, adipokines (i.e., leptin, adiponectin and TNF-alpha), insulin and blood glucose were determined before and at the end of each treatment. PRED did not induce any significant change in body weight, body composition or food intake. Insulin and TNF-alpha were not significantly altered with PRED compared to placebo but blood glucose, leptin and adiponectin concentrations at rest appear significantly increased after PRED treatment (P < 0.05). Our data show that 1 week glucocorticoid treatment does not promote obesity in recreationally trained men but further studies are necessary to understand its effects on the metabolically active hormones, leptin and adiponectin.

Effect of antioxidants combined to resistance training on BMD in elderly women: a pilot study.

SUMMARY: We determined the effect of antioxidants and resistance training on bone mineral density of postmenopausal women. After 6 months, we observed a significant decrease in the lumbar spine BMD of the placebo group while other groups remained stable. Antioxidants may offer protection against bone loss such as resistance training. INTRODUCTION: The purpose of this pilot study was to determine the effects of antioxidant supplements combined to resistance training on bone mineral density (BMD) in healthy elderly women. METHODS: Thirty-four postmenopausal women (66.1 +/- 3.3 years) were randomized in four groups (placebo, n = 7; antioxidants, n = 8; exercise and placebo, n = 11; and exercise and antioxidants, n = 8). The 6-month intervention consisted in antioxidant supplements (600 mg vitamin E and 1,000 mg vitamin C daily) or resistance exercise (3x/week). Femoral neck and lumbar spine BMD (DXA) and dietary intakes (3-day food record) were measured before and after the intervention. A repeated measure ANOVA and non-parametric Mann-Whitney U tests were used. RESULTS: We observed a significant decrease in the placebo group for lumbar spine BMD (pre, 1.01 +/- 0.17 g/cm(2); post, 1.00 +/- 0.16 g/cm(2); P < 0.05 respectively) while it remained stable in all other groups. No changes were observed for femoral neck BMD. CONCLUSIONS: Antioxidant vitamins may offer some protection against bone loss in the same extent as resistance exercise although combining both does not seem to produce additional effects. Our results suggest to further investigate the impact of antioxidant supplements on the prevention of osteoporosis.

Short-term glucocorticoid intake combined with intense training on performance and hormonal responses.

OBJECTIVE: To investigate the effects of short-term prednisolone ingestion combined with intense training on exercise performance, hormonal (adrenocorticotrophic hormone (ACTH), prolactin, luteinising hormone (LH), growth hormone (GH), thyroid-stimulating hormone (TSH), dehydroepiandrosterone (DHEA), testosterone, insulin) and metabolic parameters (blood glucose, lactate, bicarbonate, pH). METHODS: Eight male recreational athletes completed four cycling trials at 70-75% peak O(2) consumption until exhaustion just before (1) and after (2) either oral placebo or prednisolone (60 mg/day for 1 week) treatment coupled with standardised physical training (2 hours/day), according to a double-blind and randomised protocol. Blood samples were collected at rest, during exercise and passive recovery for the hormonal and metabolic determinations. RESULTS: Time of cycling was not significantly changed after placebo but significantly increased (p<0.05) after prednisolone administration (50.4 (6.2) min for placebo 1, 64.0 (9.1) min for placebo 2, 56.1 (9.1) min for prednisolone 1 and 107.0 (20.7) min for prednisolone 2). There was no significant difference in any measured parameters after the week of training with placebo but a decrease in ACTH, DHEA, PRL, GH, TSH and testosterone was seen with prednisolone treatment during the experiment (p<0.05). No significant change in basal, exercise or recovery LH, insulin, lactate, pH or bicarbonate was found between the two treatment, but blood glucose was significantly higher under prednisolone (p<0.05) at all time points. CONCLUSION: Short-term glucocorticoid administration induced a marked improvement in endurance performance. Further studies are needed to determine whether these results obtained in recreational male athletes maintaining a rigorous training schedule are gender-dependent and applicable to elite athletes.

Effects of acute prednisolone administration on exercise endurance and metabolism.

OBJECTIVE: To examine whether acute glucocorticoid (GC) intake alters performance and selected hormonal and metabolic variables during submaximal exercise. METHODS: In total, 14 recreational male athletes completed two cycling trials at 70-75% maximum O(2) uptake starting 3 h after an ingestion of either a lactose placebo or oral GC (20 mg of prednisolone) and continuing until exhaustion, according to a double-blind randomised protocol. Blood samples were collected at rest, after 10, 20, 30 minutes, and at exhaustion and recovery for measurement of growth hormone (GH), adrenocorticotropic hormone (ACTH), dehydroepiandrosterone (DHEA), prolactin, insulin, blood glucose, lactate and interleukin (IL)-6 determination. RESULTS: Cycling duration was not significantly changed after GC or placebo administration (55.9 (5.2) v 48.8 (2.9) minutes, respectively). A decrease in ACTH and DHEA (p<0.01) was observed with GC during all of the experiments and in IL-6 after exhaustion (p<0.05). No change in basal, exercise or recovery GH, prolactin, insulin or lactate was found between the two treatments but blood glucose was significantly higher with GC (p<0.05) at any time point. CONCLUSION: From these data, acute systemic GC administration does seem to alter some metabolic markers but did not influence performance during submaximal exercise.

Preserved bone health in adolescent elite rhythmic gymnasts despite hypoleptinemia.

BACKGROUND/AIMS: Leptin is linked to hormonal disturbances occurring in anorexia and positively linked with bone mineral density. The aim of this study was to determine whether hypoleptinemia occurring in rhythmic gymnasts may affect bone health. METHOD: Leptin, insulin, cortisol, IGF1 levels and bone markers were determined in 36 rhythmic gymnasts (EG) and 20 controls (C). Body composition, BMD at the whole body (WBBMD), lumbar spine (LSBMD) and bone ultrasound properties (SOS, BUA) were measured. RESULTS: The rhythmic gymnasts had lower fat mass and leptin level than the controls. There was no difference for IGF1, cortisol and insulin levels. Bone turnover rate was higher in elite gymnasts. The uncoupling index showed that remodeling favored the bone formation. LSBMD, WBBMD, SOS and BUA were higher in elite gymnasts after adjustment for fat mass. Leptin correlated positively with fat mass and negatively with physical activity. CONCLUSION: High impact training is able to counterbalance bone effects usually encountered in hormonally disturbed subjects. Our results suggest that hypoleptinaemia might be related to direct osteogenic effects and indirect hormonal mechanisms including preservation of IGF and cortisol levels.

Substrate oxidation during exercise in the rat cannot fully account for training-induced changes in macronutrients selection.

This study investigated spontaneous dietary adaptation to regular exercise in relation to substrate oxidation measured during exercise. Male Wistar rats were offered permanent access to the three sources of macronutrients supplemented with minerals and vitamins. The rats remained sedentary or were trained daily during 3 weeks at moderate intensity (20 m x min(-1), 2 hours). Body weight, total caloric intake, and macronutrients selection were recorded throughout the experiment. Energy expenditure and substrate oxidation were measured before, during, and after an exercise identical for trained and untrained rats (10 m x min(-1) 1 hour). Training reduced body weight gain (2.27 v 5.57 g x day(-1)), increased protein intake (52.6% v 39.2%), and decreased carbohydrate intake (21.3% v 39.5%). Basal and running energy expenditure, as well as glucose and lipid oxidation, remained essentially comparable in trained and untrained rats. The relative contribution of glucose oxidation (Gox) to total energy expenditure decreased during exercise (52.2%, average of all rats) relative to before exercise (60.8%). Gox during exercise was positively correlated with resting Gox before exercise, showing that preexercise substrate oxidation was a strong determinant of running substrate oxidation. However, the slope was smaller for the trained than for the untrained rats, showing that exercise increases Gox less in trained rats than in untrained ones. We conclude from this study that, since food selection but not substrate oxidation changed following training, food intake adapted to substrate requirements induced by regular training and not the contrary. However, large differences remained between the mixture ingested, in which lipids accounted for only 26% of the energy, and the mixture oxidized during exercise, in which lipids accounted for 50.7% of the substrate oxidized. Such a difference may be related to metabolic requirements during the rest of the day and/or to the distribution of macronutrients intake relative to exercise. This question deserves further investigation with recording of macronutrients selection, energy expenditure, and substrate oxidation over 24 hours.

Exercise training decreases body fat more in self-selecting than in chow-fed rats.

This study was designed to examine the influence of exercise training on body weight gain and feeding pattern in rats placed on a self-selection or a chow diet regimen. Adult, male, Wistar rats were submitted to daily 2-h treadmill exercise for 28 days (about 50% of VO2 max) at the beginning of the nocturnal period. Two other groups of rats were examined during the same time: a sedentary group that was deprived of food and water during the training session and a control group without any treatment. Food intakes were continuously recorded. For both feeding regimens, trained rats, relative to their respective controls, showed at the end of the experiment a reduction in body weight gain due to a reduced body fat deposit. Moreover, white adipose tissue (WAT) mass of self-selecting rats was smaller than in chow-fed rats. Exercise training decreased plasma glucose level in chow-fed rats and plasma insulin level in self-selecting rats. In self-selecting rats, food intake was slightly increased due to enhanced protein intake during the nocturnal period and fat intake increased both during the nighttime and daytime periods, whereas in chow-fed rats, food intake was decreased during the daytime period. These results show that, in rats placed on a self-selection regimen, exercise training increased fat consumption but reduced WAT. This could be a consequence of an increased lipolytic capacity of adipocytes in self-selecting trained rats. Thus, it appears from these results that the diet's carbohydrate-to-fat ratio can be an important parameter in shaping the interaction between exercise and body weight.

Exercise-training reduces BAT thermogenesis in rats.

In the energy balance equation, physical activity represents one component of energy expenditure. From various studies it appears that exercise-training does not affect clearly thermogenesis which depends on brown adipose tissue (BAT) activity. In the present work we examine how exercise-training can influence food intake and body weight regulation in relation to BAT thermogenesis. The proton conductance of the uncoupling protein of BAT was examined in male adult Wistar trained 2 h/day for 20 days and compared to that of sedentary (2 h of fasting instead of exercise) or control animals. All animals were provided with separate sources of the 3 macronutrients (protein, fat and carbohydrate) containing an identical percentage of vitamins, salt mixture and cellulose powder. At the end of training, rats were placed at 5 degrees C during 10 days, then during 4 days at 28 degrees C. This condition has been demonstrated to favour and amplify BAT responsiveness to moderate modifications of stimulation. The body weight of trained rats became significantly lower than that of the control and sedentary rats and this difference persisted all throughout the experiment. When placed at 5 degrees C, all rats increased their total ingestion: control rats enhanced fat intake, while sedentary and trained rats enhanced carbohydrate ingestion. When placed at 28 degrees C, all rats had identical total energy and that of the 3 items intakes. BAT proton conductance was about 40% lower in the trained compared with the sedentary plus the control rats. This indicated a lower BAT thermogenic activity in the trained animals. It could be concluded that exercise-training in rats induces negative energy balance; the reduced BAT activity could restrain weight loss and overeating.

Exercise training modifies nutrient self-selection in rats.

Few studies have examined the effects of exercise training on macronutrient self-selection in rats. It has been observed that trained rats decreased carbohydrate and increased fat and protein intakes. In the present experiment, total energy intake and macronutrient self-selection were examined in adult male rats placed on a self-selection regimen and submitted to 2 h of treadmill exercise daily for 20 days at the beginning of the nocturnal period. Two control groups of rats were examined during the same time: a sedentary group that was food and water deprived during the same 2 h while trained rats were exercising, and a control group that was examined only for body weight gain and 24-h food intake. Food intakes of sedentary and trained rats were continuously recorded. At the end of the experiment, body weight of trained rats was lower than that of sedentary and control rats. The 24-h cumulative intake of trained rats was significantly reduced; this reduction was due to a decrease in fat intake, whereas carbohydrate intake was increased. In sedentary rats, 24-h intake was not modified but fat intake was significantly increased from the beginning to the end of the experiment. During the first 6 h of the night, protein and fat intakes of trained rats were reduced, and carbohydrate ingestion remained the same. Daytime food intake represented only 8.7% of the 24-h intake. Exercise training significantly increased this intake. It is noteworthy that during the middle part of the day (3-9 h) trained rats significantly enhanced protein and carbohydrate ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)