Twenty-four hour growth hormone and leptin secretion in active postpubertal adolescent girls: impact of fitness, fatness, and age at menarche.

CONTEXT: GH is strongly related to body composition, physical activity, and pubertal progression. Adolescent girls decrease physical activity during puberty, whereas their weight increases. Because leptin is a good index of energy balance in active young women, we hypothesized that leptin is related to GH secretion in this population while taking into account fitness, fatness, and age at menarche. METHODS: We measured body composition and maximal oxygen consumption (VO(2)max) in 37 postpubertal adolescent girls aged 16-21 yr. GH was sampled every 10 min and leptin hourly for 24 h. We first analyzed 6-h time blocks by repeated measures for GH and leptin, with body mass index (BMI), percent body fat, and VO(2)max as covariates for the entire group and a lean subgroup. The deconvolution method was used to characterize GH pulsatility from individual time points. RESULTS: GH varied through the day (P < 0.0001), with the highest concentrations overnight. BMI, percent body fat, and VO(2)max were related to GH concentrations in the entire group, whereas leptin predicted GH in the entire group as well as the lean subgroup of girls. Higher leptin was related to lower GH concentrations (P = 0.011), regardless of time. A log leptin level increase by 1 unit decreased GH by 27%. Pulsatility characteristics showed a 1-yr increase of age at menarche increasing total GH input by 20% (P = 0.0035) independently from BMI. CONCLUSION: In postpubertal adolescent girls, leptin is related to GH concentration across the lean to overweight BMI spectrum. GH pulsatile secretion was greater in girls with later age at menarche.

Does exercise affect female hamster gonadotropins by reducing estradiol negative feedback?

Exercise stimulates reproductive function in hamsters exposed to short-day photoperiod (SDP) in contrast to its inhibitory effects in women and rats. SDP inhibits hamster reproduction in part by increasing the sensitivity of the hypothalamo-pituitary-gonadal axis (HPGA) to the negative feedback of gonadal steroids. To determine whether EX facilitates reproduction in female hamsters by affecting this mechanism, we examined the influence of estradiol (E2) on basal LH and FSH concentrations in exercising and sedentary hamsters maintained on long-day photoperiod (LD 14:10, LDP) or SDP (LD 8:16). In the LDP, serum LH and FSH were unaffected or reduced by exercise in ovariectomized (OVX) nonhormone-replaced hamsters, and LH was increased after tonic E2 replacement compared to sedentary controls. In the SDP, serum LH and FSH were significantly higher in OVX exercising than in sedentary hamsters, whether the exercisers were injected with a high dose of E2 or not. Thus, the effects of exercise on basal gonadotropin secretion in female hamsters appear to depend on the level of estradiol negative feedback (ENF). When this feedback is low (LDP OVX condition), exercise is either ineffective or inhibitory. When the ENF is increased by exposure to SDP and/or by treatment with E2, exercise has a stimulatory effect on basal gonadotropin secretion. Exercise may stimulate hamster gonadotropin secretion by reducing the ENF either by lowering the sensitivity of the HPGA to steroid negative feedback or by other means.

The effects of exercise on growth.

The way in which exercise influences statural, hypertrophic and reparative growth is examined from the perspective of the human lifespan. Statural growth depends on a neuroendocrine programme which channels nutrient energy towards increments in lean body mass. Exercise can facilitate statural growth and is a necessary stimulus for reparative growth through its stimulatory effects on secretion of growth hormone (GH) and other anabolic hormones. An exercise-associated increase in GH secretion is a response to acute or prolonged exercise-induced fuel shortage that directs metabolism towards utilisation of lipids and promotes growth. Exercise can transiently block the expression of statural growth by competitively removing the necessary nutritional support for growth. Statural growth retardation can be corrected by catch-up growth, but stunting may also be permanent (depending on the timing and magnitude of the energy drain). Hypertrophic growth is less dependent on hormonal and nutritional support than statural growth, and exercise provides the necessary mechanical stress for growth and remodelling of the musculoskeletal system. Excessive mechanical strain may suppress hypertrophic growth. The intermittent nature of exercise provides temporal organisation that is necessary for the normal operation of cellular growth process. Exercise by pregnant women does not appear to influence fetal growth. Evaluation of the effect of exercise on growth of children and adolescents is complicated by nonrandom selection of individuals for participation in organised sports, and by lack of information on the magnitude of exercise-induced energy drain. Exercise is essential for regulation of body composition in adulthood. It provides mechanical and metabolic stimuli that are necessary for hypertrophy of the musculoskeletal system and increased GH secretion for reparative growth.

Effect of voluntary exercise and food restriction in response to lipopolysaccharide in hamsters.

We tested the hypothesis that voluntary running and moderate food restriction alter the acute phase response (APR), one index of nonspecific immune function. Hamsters were kept sedentary or permitted to run and were fed ad libitum or had food restricted for 20 days and were then injected intraperitoneally with saline or lipopolysaccharide (LPS). Fever and circulating interleukin-6, serum amyloid A (SAA), serum iron, and cortisol were measured by biotelemetry, B-9 cell growth assay, indirect enzyme-linked immunosorbent assay, colorimetric analysis, and radioimmunoassay, respectively. The febrile temperature; hypoferremia; and elevation of circulating interleukin-6, SAA, and cortisol after LPS injection were not altered by exercise. Because baseline temperatures were elevated in the exercised hamsters, the change in temperature in response to LPS was less than it was in the sedentary hamsters. Food restriction significantly decreased SAA and elevated cortisol after LPS injection and depressed the absolute temperature to which the core temperature rose in response to LPS in one trial but not in another. Because food restriction depressed baseline temperatures, it also affected the change in temperature after LPS injection. The hypoferremic response to LPS was inhibited in hamsters that were both food restricted and permitted to run. We conclude that exercise does not enhance the APR to a low dose of LPS, whereas food restriction and the combination of exercise and food restriction depress some portions of the APR in hamsters.

Effect of exercise and food restriction on selected markers of the acute phase response in hamsters.

Acute aerobic exercise has been shown to elicit physiological changes characteristic of the acute phase response (APR), a nonspecific host defense response. Regular evocation of these changes may prime the immune system to improve resistance to disease. Because food deprivation is associated with an impaired APR, food restriction may prevent these beneficial changes. We tested the hypotheses that voluntary exercise elicits an APR and that food restriction modifies this response in four groups of hamsters: ad libitum-fed sedentary, ad libitum-fed exercised, food-restricted sedentary, and food-restricted exercised. Five variables altered during an APR were examined: core temperature, serum iron, serum interleukin-6, serum amyloid A, and serum glucocorticoids measured by biotelemetry, colorimetric analysis, B-9 cell growth assay, indirect enzyme-linked immunosorbent assay, and radioimmunoassay, respectively. Blood was drawn during the hamsters' inactive period after 19-20 days of access to running wheels. Resting core temperature was elevated by exercise and depressed by food restriction (P < 0.01). Iron was depressed by food restriction (P < 0.01). Cortisol, but not corticosterone, was elevated by food restriction (P < 0.001). There were no significant differences among groups in interleukin-6 (P > 0.49) or serum amyloid A (P > 0.29). We conclude that there is little evidence that voluntary exercise or exercise combined with food restriction causes an APR in hamsters.

Control by light of the temperature rhythm in food-restricted hamsters.

To establish the relative importance of light and food in the control of core temperature (Tc) rhythm in food-restricted hamsters, mature female hamsters maintained in 14L:10D lighting were fed restricted amounts of food at the onset of light (n = 6) or at the onset of dark (n = 6) and were compared to ad lib-fed animals. After 21-25 days of this entrainment, light stimulus was shifted by 12 h, and animals were kept in shifted lighting for another 13 days. Food restriction led to a 0.6 degree decrease in the mean Tc, which was expressed entirely during the day in night-fed hamsters and was evenly divided between day and night in day-fed animals. Thus, Tc and general activity rhythms maintained the entrainment to light under both dietary conditions, with peak values for all occurring during the early night. During 13 days following the 12-h shift in lighting, Tc and activity rhythms shifted in all animals, regardless of nutritional status, from entrainment to preceding lighting, through double rhythm frequency, indicating entrainment to preceding as well as current lighting, to entrainment to current lighting. Thus, in food-restricted hamsters, light stimulus rather than predictable timing of food prevails as the entrainer of Tc and activity rhythms.

Neurohumoral mediation of exercise-induced growth.

To assess exercise effects on growth, other variables modulating growth need to be taken into account. Endogenous control of growth proceeds from local actions of growth factors and dependence on nutrition abundance through guidance by growth hormone (GH) and other anabolic hormones to neuroendocrine suppression of growth. Nutrient abundance controls the reparative growth of lean body mass in adulthood by coupling it to anabolic endocrine reflexes. Growth is blocked when catabolic endocrine reflexes govern energy expenditure. The relationship between exercise intensity and growth is nonlinear. Growth is an intermittent process. Its expression and stimulation are dependent on ultradian and circadian rhythms of energy metabolism and neurohumoral release. High-resistance exercise selectively stimulates growth of the musculoskeletal system through expression of growth factor genes in the challenged tissues and without the GH guidance or abundant nutritional support. Habitual endurance exercise stimulates reparative growth of lean body mass through the neuroendocrine adaptations including increased pulsatile GH secretion. These also facilitate oxidative utilization of storage lipids thereby contributing to the regulation of body composition in adulthood. In the absence of sufficient high-resistance and endurance exercise regulation of adult body mass is impaired: excess LBM is lost during energy deficit, and excess fat accumulates during energy surplus.

Tumor necrosis factor is not involved in exercise-induced elevation in core temperature.

Female Sprague-Dawley rats (12:12-h light-dark photoperiod) with access to running wheels have an elevated body temperature (BT) both during exercise (nighttime) and nonexercise periods (daytime). We studied whether the exercise-induced increase in BT is modulated by the release of the cytokine, tumor necrosis factor-alpha (TNF). Two weeks after the onset of exercise, nighttime temperatures of exercising rats were elevated approximately 0.5 degree C compared with preexercise values (P = 0.006). By 3 wk after the onset of exercise, daytime temperatures had increased 0.3 degree C (P = 0.03) above control levels. To confirm that endogenously produced TNF can modulate fever in female rats, we injected six rats with antiserum to TNF (300 microliters/rat) and six rats with control serum 24 h before intraperitoneal injection of lipopolysaccharide (50 micrograms/kg). As occurred in earlier studies on male rats, antiserum-treated female rats had significantly enhanced fevers (P = 0.017). To determine whether endogenously produced TNF was involved in modulating the daytime and nighttime increases in BT, antiserum to TNF (300 microliters/rat, n = 7) or control serum (300 microliters/rat, n = 5) was injected intraperitoneally in exercising rats. Neither injection of antiserum nor control serum had any effect on daytime or nighttime BTs. Because BTs of exercising female rats injected with antiserum against TNF were not affected, we conclude that TNF is not responsible for modulating their exercise-induced rise in BT.

Role of prostaglandins in exercise-induced core temperature elevation in female Sprague-Dawley rats.

Female Sprague-Dawley rats (12:12-h photoperiod; body temperature, BT, measured with biotelemetry) with access to running wheels for 6 wk have an elevated BT (compared with rats with no access to exercise wheels, i.e, sedentary) both during the period of voluntary exercise (nighttime) (0.5 degree C, P = 0.0001) and the nonexercise period (daytime) (0.3 degree C, P = 0.002). To determine whether prostaglandin (PG) E was responsible for any portion of this daytime rise in BT, we injected a dose of sodium salicylate (300 mg/kg), which was shown to produce complete antipyresis in rats injected with lipopolysaccharide (LPS), into exercised and sedentary rats 4 h after the onset of the lights-on period. The injections of sodium salicylate led to a fall in body temperature in both the exercised and sedentary rats of similar amounts (-0.88 degree C vs. -0.61 degree C at 2 h postinjection, P = 0.59). We conclude that the increase in daytime BT of exercised female rats is not mediated by prostaglandins.

Food restriction postpones, not prevents, exercise-induced growth in hamsters.

Voluntary exercise during ad libitum feeding accelerates growth in mature female hamsters. If food is restricted during the exercise period, growth is suppressed, but ad libitum access to food at the cessation of exercise permits rapid catch-up growth in length and weight during retirement. To see whether the exercise-induced stimulus to grow persists when food-restriction is continued during retirement, female golden hamsters were matched by weight and assigned to exercise (EX) and sedentary (SED) groups fed ad libitum and to corresponding activity groups (REST-EX, REST-SED) food-restricted to 80% of starting weight. At the end of each week for 3 weeks following retirement, one REST-EX and one REST-SED group were fed ad libitum. At 21-35 days post-refeeding, mean gains in length and weight of each exercise group were greater (p < 0.05) than the gains of the corresponding sedentary group. Thus, exercise under food restriction remained an effective stimulus for acceleration of growth throughout three weeks of continued food restriction beyond termination of exercise, and ad libitum feeding permitted the delayed expression of exercise-induced catch-up growth in hamsters.

Stimulation by voluntary exercise of adrenal glucocorticoid secretion in mature female hamsters.

The possibility that habitual voluntary running induces a chronic change in adrenal glucocorticoid synthesis and secretion was examined in freely running mature female hamsters, in whom this behavior accelerates growth, reduces body fat levels, and elevates core temperature. Hamsters were free to run on horizontal discs or in vertical wheels between 32 and 80 days, in 14L:10D or in 10L:14D photoperiods, and at the end of this period, corticosterone and cortisol steroidogenesis and serial plasma corticosterone concentrations during day and night were used as measures of the chronic stimulation of adrenal cortical activity. Habitual voluntary running significantly increased steroidogenesis of both glucocorticoids and plasma corticosterone concentrations and alone accounted for all the variance in enhanced synthesis and secretion of corticosterone. Acute exercise and/or the nocturnal phase of circadian period enhanced the chronic stimulatory effects of exercise on cortisol. Despite its voluntary and apparently stress-free nature, running induces chronic increases in basal glucocorticoid secretion in mature female hamsters. Putative oversecretion of corticotropin releasing factor in freely running hamsters could account for increased steroidogenesis, acceleration of growth, reduced body fat levels, and core temperature elevation.

Activity disc and cage for continuous measurement of running activity and core temperature in hamsters.

We describe a design for the modular horizontal activity disc and tandem cages suitable for continuous monitoring of spontaneous running and of core temperatures in golden hamsters. An acrylic disc is equipped with a short brass axle. It is mounted inside a brass rotation sleeve at a 15 degrees angle off the horizontal plane. The disc module fits firmly inside either half of the tandem cage when activity measurements are needed. Easy removal allows for alternative use of cages. Minor modifications of disc dimensions and of disc base permit the use of activity modules with juvenile hamsters. The short distance between disc surface and cage floor permits continuous measurement of core temperature as well as running activity.

Body temperature rhythm and response to pyrogen in exercising and sedentary hamsters.

In this study, we tested the hypothesis that daily voluntary exercise results in a chronic elevation in core temperature in the female golden hamster. Temperature and activity were measured by biotelemetry. Hamsters ran 6-7 km per night (12:12 L:D) when permitted access to wheels. No running occurred during the light periods. During the 3rd wk of running, temperatures of exercising hamsters were significantly elevated by 0.5 degree C (P less than 0.001) during the dark period and by 0.3 degree C (P less than 0.003) during the light period compared with sedentary hamsters. Cessation of running removed the difference between groups, and resumption of running restored it. Both the injection of endotoxin and the psychological stress of cage switch resulted in similar peak temperatures in exercising and sedentary hamsters despite higher pre-treatment temperatures in the exercise group. We interpret these results to support the hypothesis that regular exercise may cause an upward resetting of the set-point for body temperature.

Melatonin increases serum growth hormone and insulin-like growth factor I (IGF-I) levels in male Syrian hamsters via hypothalamic neurotransmitters.

In male Syrian hamsters daily evening melatonin injections resulted in increased circulating levels of growth hormone (GH), as well as a modest increase in body weight. A substantial increase in serum levels of insulin-like growth factor I (IGF-I) was observed in all hamsters receiving evening injections of melatonin for 10 weeks. The melatonin-induced increase in serum IGF-I levels was interpreted as a result of increased release of GH during the 10 week period of melatonin administration. The increase in serum GH and IGF-I was associated with significantly decreased hypothalamic turnover of norepinephrine (NE). Since blocking NE synthesis with alpha methyl-p-tyrosine reduced serum GH, the melatonin-induced increase in GH could not readily be attributed to decreased NE turnover. Highly significant increases in 5-hydroxyindole acetic acid (5HIAA) concentrations and in ratios of 5HIAA to serotonin (5HT) were noted in extracts of hypothalamus and in extracts of brain stem, suggesting a serotonergic component to melatonin-induced increase in GH-induced IGF secretion and subsequent growth.

Hippocampal serotonin mediates hypoactivity in dietarily obese hamsters: a possible manifestation of aging?

To determine whether endogenous opiates mediate hyperactivity in food restricted hamsters and serotonergic fibers innervating the hippocampus mediate hypoactivity in obese hamsters, food restriction and high-fat diet supplementation were used to produce significant body fat changes (8 vs. 21%). The levels and pattern of spontaneous running were examined after IP saline or naloxone HCl (20 mg/kg) and following the infusion of vehicle and 5,7-dihydroxytryptamine creatine sulfate (4 micrograms/2 microliters) into rostromedial septum of mature female hamsters. Septum-medial preoptic area (POA), hippocampus, hypothalamus, and cortex were dissected from the three groups as well as from two additional groups of hamsters receiving vehicle or neurotoxin. Concentrations of serotonin, norepinephrine, and dopamine were measured in these tissues by HPLC method. Fat-fed hamsters were hypoactive relative to food-restricted hamsters. Naloxone had no significant effect on running behavior. Serotonin neurotoxin increased the running activity of fat-fed hamsters to the level displayed by control hamsters by increasing the number of runs, the total activity level, the speed of running and by decreasing the duration of pauses. Neurotoxin led to selective deletion of serotonin in the hippocampus (77%) and parietal cortex (50%). Serotonergic fibers innervating the hippocampus thus appear to mediate the hypoactivity that is induced by dietary obesity in mature hamsters. Since serotonin mediates some other manifestations of aging, and slow weight increases characterize mid-portion of hamster life span, we hypothesize that serotonergic mediation of hypoactivity is another manifestation of aging.

Exercise inhibits reproductive quiescence induced by exogenous melatonin in hamsters.

Voluntary exercise inhibits the reproductive regression associated with a short photoperiod in male or female hamsters. The question addressed by the present study was whether exercise would also attenuate the reproductive regression associated with injection of exogenous melatonin. In male hamsters exercise inhibited the testicular regression, decline in gonadotropin secretion, and reduction in testosterone release associated with two daily injections (15 micrograms) of melatonin in pinealectomized hamsters on long days. After the reproductive system of the sedentary melatonin group had regressed, one-half of these hamsters were placed in cages with exercise wheels. Access to the exercise wheels stimulated testicular recrudescence and restored gonadotropin secretion to levels found in vehicle-injected hamsters. Sedentary female hamsters injected with melatonin tended to go into a state of constant diestrus associated with daily afternoon increases in serum luteinizing hormone, whereas most exercising hamsters injected with melatonin generally continued having regular estrous cycles with proestrus luteinizing-hormone surges. The ability of exercise to inhibit the effect of exogenous melatonin in pinealectomized hamsters suggests that exercise acts, at least in part, by mechanisms other than altering melatonin secretion.

Group housing accelerates growth and induces obesity in adult hamsters.

To determine whether variable body heat loss may influence control of growth and regulation of body fat content in hamsters, mature female hamsters were housed for 7-14 wk in one of three conditions: individually in metal cages (n = 6), individually in plastic boxes with bedding (n = 6), or communally (6 per box) in plastic boxes with bedding. Their resting metabolic rate (RMR) was measured individually or in pairs of two between days 65 and 75. When thermal properties of shelter varied alone, singly housed hamsters regulated energy balance fairly accurately by compensatory changes in food intake, and their rate of growth was unaffected. In contrast, group housing induced acceleration of growth and obesity without hyperphagia, was associated with an acute inhibition of RMR in hamsters tested in pairs, and was associated with a chronic inhibition of RMR in hamsters tested individually. We conclude that conspecific body contact in mature group-housed hamsters accelerates somatic growth and increases fat deposition. Energy for this anabolism is derived, in part, from reduced RMR and, in part, from a slight increase in food consumption.

Exercise-induced hyperphagia in the hamster is associated with elevated plasma somatostatin-like immunoreactivity.

Syrian golden hamsters when allowed free access to food and an exercise wheel will run long distances and develop hyperphagia and accelerated linear body growth with high circulating levels of growth hormone and insulin. Somatostatin, a widely distributed brain-gut neurohormonal peptide, modulates nutrient absorption and may regulate food intake. To examine the role of circulating plasma somatostatin-like immunoreactivity (SRIF-LI; pg/ml) in exercise induced hyperphagia 4 groups of animals were studied; an unrestricted exercise group (279.0 +/- 107.7, n = 10); a sedentary group (121.1 +/- 40.8, n = 8); a restricted exercise group (107.7 +/- 12.4, n = 6); and a restricted no exercise group (115.5 +/- 45.9, n = 9). Thus, the unrestricted exercise group has a significantly elevated SRIF-LI concentration (P less than 0.01) while there was no difference between the other 3 groups. The elevation of plasma SRIF-LI in the unrestricted exercise group may represent a response to modulate increased nutrient entry in this group or may represent an incompletely effective satiety signal.

Rostromedial septal area controls pulsatile growth hormone release in the golden hamster.

Limbic forebrain inhibits growth and growth hormone (GH) secretion in mature golden hamsters as shown by acceleration of growth and increases in serum GH concentrations following the electrolytic lesions of septum, transection of the hippocampus and surgical separation of these two regions. The growth-inhibitory function of this circuit is most probably mediated by somatostatinergic (SRIF) neurons. Such lesions induce hypoactivity possibly due to damage to endogenous opiatergic (EOP) neurons. EOP neurons facilitate spontaneous running in hamsters and mediate exercise-induced acceleration of growth and GH pulses. The coincidence of hypoactivity and growth acceleration after such lesions suggested the coexistence of SRIF and EOP fibers within the growth-inhibitory limbic forebrain circuit which control the rate of growth in mature hamsters by the variable inhibition of SRIF neurons by the EOP neurons. This hypothesis posits that accelerated growth is due to increased GH pulse frequency, and hypoactivity due to damage to EOP neurons, and was tested in this study by measuring pulsatile GH release (and as a measure of specificity, pulsatile prolactin release) in the presence and in the absence of opiate-receptor blocker naloxone in 21 female hamsters which sustained electrocoagulative lesions of rostromedial septum and 30 hamsters subjected to control surgery. Lesions doubled GH but not PRL pulse frequency, neither of which was affected by naloxone. Results support the hypothesis that opiatergic neurons facilitate pulsatile GH release by inhibiting the action of somatostatin neurons.

The effects of age on substrate depletion and hormonal responses during submaximal exercise in hamsters.

Senescent hamsters display a marked reduction in volume of voluntary running. The purpose of this study was to determine whether age differences exist in the pattern of fuel utilization during submaximal exercise, which may account for the reduction in voluntary running. Further, we determined the effects of age on muscle oxidative capacity to assess its relationship to endurance performance in senescent hamsters. Depletion of carbohydrate and lipid content of skeletal muscle and liver, and changes in blood concentration of various hormones and substrates during one hour of exercise at 60 percent of VO2 max served to assess age effects on utilization of metabolic substrates. Exercise produced equivalent depletion of muscle glycogen and similar rise in plasma free fatty acids in young and old hamsters. No exercise effects on skeletal muscle triglyceride concentration or on plasma glycerol, glucagon or catecholamine concentrations were noted. With palmitoyl carnitine as substrate (but not with pyruvate) State 3 respiration of cardiac and skeletal muscle homogenates was lower in old compared to young hamsters. Although old hamsters have a reduced capacity to oxidize lipids in vitro, few age differences in fuel use are evident in vivo during submaximal exercise. Thus, these minor age differences in substrate utilization do not likely account for the substantial reduction in the levels of spontaneous running in senescent hamsters.