Growth hormone-releasing peptide-2 infusion synchronizes growth hormone, thyrotrophin and prolactin release in prolonged critical illness.
OBJECTIVE: During prolonged critical illness, nocturnal pulsatile secretion of GH, TSH and prolactin (PRL) is uniformly reduced but remains responsive to the continuous infusion of GH secretagogues and TRH. Whether such (pertinent) secretagogues would synchronize pituitary secretion of GH, TSH and/or PRL is not known. DESIGN AND METHODS: We explored temporal coupling among GH, TSH and PRL release by calculating cross-correlation among GH, TSH and PRL serum concentration profiles in 86 time series obtained from prolonged critically ill patients by nocturnal blood sampling every 20 min for 9 h during 21-h infusions of either placebo (n=22), GHRH (1 microg/kg/h; n=10), GH-releasing peptide-2 (GHRP-2; 1 microg/kg/h; n=28), TRH (1 microg/kg/h; n=8) or combinations of these agonists (n=8). RESULTS: The normal synchrony among GH, TSH and PRL was absent during placebo delivery. Infusion of GHRP-2, but not GHRH or TRH, markedly synchronized serum profiles of GH, TSH and PRL (all P< or =0.007). After addition of GHRH and TRH to the infusion of GHRP-2, only the synchrony between GH and PRL was maintained (P=0.003 for GHRH + GHRP-2 and P=0.006 for TRH + GHRH + GHRP-2), and was more marked than with GHRP-2 infusion alone (P=0.0006 by ANOVA). CONCLUSIONS: The nocturnal GH, TSH and PRL secretory patterns during prolonged critical illness are herewith further characterized to include loss of synchrony among GH, TSH and PRL release. The synchronizing effect of an exogenous GHRP-2 drive, but not of GHRH or TRH, suggests that the presumed endogenous GHRP-like ligand may participate in the orchestration of coordinated anterior pituitary hormone release. (+info)
Long-term results of GH therapy in GH-deficient children treated before 1 year of age.
OBJECTIVES: To evaluate the long-term effects of GH therapy in early diagnosed GH-deficient patients treated before 1 year of age. STUDY DESIGN: We studied all 59 patients (33 males) recorded by Association France-Hypophyse and treated with GH (0.50+/-0.15 IU/kg (S.D.) per week) before 1 year of age. Clinical presentation and growth parameters under GH treatment were analyzed. RESULTS: Neonatal manifestations of hypopituitarism were frequent: hypoglycemia (n=50), jaundice (n=25) and micropenis (n=17/33). Although birth length was moderately reduced (-0.9+/-1.4), growth retardation at diagnosis (5.8+/-3.8 months) was severe (-3.5+/-1.9 standard deviation scores (SDS)). Fifty patients (85%) had thyrotropin and/or corticotropin deficiency. After a mean duration of GH therapy of 8.0+/-3.6 years, change in height SDS was +3.11+/-2.06 S.D., exceeding 4 SDS in 19 patients. Only 9 patients (15%) did not reach a height of -2 S.D. for chronological age and 20 patients (34%) exceeded their target height. Pretreatment height SDS was independently associated with total catch-up growth. CONCLUSION: Conventional doses of GH allow normalization of height in patients with early GH deficiency and treatment. (+info)
Changes in body composition and leptin levels during growth hormone (GH) treatment in short children with various GH secretory capacities.
OBJECTIVE: The aim of this study was to follow changes in body composition, estimated by dual-energy X-ray absorptiometry (DXA), in relation to changes in leptin during the first year of GH therapy in order to test the hypothesis that leptin is a metabolic signal involved in the regulation of GH secretion in children. DESIGN AND METHODS: In total, 33 prepubertal children were investigated. Their mean (S.D.) chronological age at the start of GH treatment was 11.5 (1.6) years, and their mean height was -2.33 (0.38) S.D. scores (SDS). GH was administered subcutaneously at a daily dose of 0.1 (n=26) or 0.2 (n=7) IU/kg body weight. Ten children were in the Swedish National Registry for children with GH deficiency, and twenty-three children were involved in trials of GH treatment for idiopathic short stature. Spontaneous 24-h GH secretion was studied in 32 of the children. In the 24-h GH profiles, the maximum level of GH was determined and the secretion rate estimated by deconvolution analysis (GHt). Serum leptin levels were measured at the start of GH treatment and after 10 and 30 days and 3, 6 and 12 months of treatment. Body composition measurements, by DXA, were performed at baseline and 12 months after the onset of GH treatment. RESULTS: After 12 months of GH treatment, mean height increased from -2.33 to -1.73 SDS and total body fat decreased significantly by 3.0 (3.3)%. Serum leptin levels were decreased significantly at all time points studied compared with baseline. There was a significant correlation between the change in total body fat and the change in serum leptin levels during the 12 months of GH treatment, whereas the leptin concentration per unit fat mass did not change. In a multiple stepwise linear regression analysis with 12 month change in leptin levels as the dependent variable, the percentage change in fat over 12 months, the baseline fat mass (%) of body mass and GHt accounted for 24.0%, 11.5% and 12.2% of the variability respectively. CONCLUSIONS: There are significant correlations between changes in leptin and fat and endogenous GH secretion in short children with various GH secretory capacities. Leptin may be the messenger by which the adipose tissue affects hypothalamic regulation of GH secretion. (+info)
Hormone-related, muscle-specific changes in protein metabolism and fiber type profile after faba bean intake.
Male growing Wistar rats were fed, over 15 days, isoenergetic (16.72 +/- 0.49 MJ) and isoproteic (11%) diets containing either lactalbumin or raw Vicia faba L. (Vf) as the sole source of protein. Compared with pair-fed controls (PF), soleus muscles of Vf-fed rats showed increased (P < 0.05) synthesis and breakdown rates. In addition, the soleus of Vf-fed rats displayed a decrease (P < 0.05) in type I and an increase (P < 0.01) in type IIc fibers compared with that of PF animals. On the contrary, extensor digitorum longus muscles of both Vf-fed and PF rats showed an increase (P < 0.01) in type I and a reduction (P < 0.05) in type IIb fibers together with a decrease (P < 0.05) in the cross-sectional area of the latter fibers. Vf-fed rats exhibited a significant decrease in serum insulin (P < 0.05) and thyrotropin (P < 0.01) levels, together with an increase in plasma glucagon (P < 0.05) and 3,5,3'-triiodothyronine (P < 0.01) concentrations, compared with the PF group. Both Vf-fed and PF rats experienced an increase in corticosterone concentrations (P < 0.01 vs. control; P < 0.05 vs. PF). The muscle-specific changes in both protein metabolism and fiber type composition may partly depend on the hormonal changes that were observed after Vf intake. (+info)
Mechanism for the posture-specific plasma volume increase after a single intense exercise protocol.
To test the hypothesis that exercise-induced hypervolemia is a posture-dependent process, we measured plasma volume, plasma albumin content, and renal function in seven healthy subjects for 22 h after single upright (Up) or supine (Sup) intense (85% peak oxygen consumption rate) exercise. This posture was maintained for 5 h after exercise. Plasma volume decreased during exercise but returned to control levels by 5 h of recovery in both postures. By 22 h of recovery, plasma volume increased 2.4 +/- 0.8 ml/kg in Up but decreased 2.1 +/- 0.8 ml/kg in Sup. The plasma volume expansion in Up was accompanied by an increase in plasma albumin content (0.11 +/- 0.04 g/kg; P < 0.05). Plasma albumin content was unchanged in Sup. Urine volume and sodium clearance were lower in Up than Sup (P < 0.05) by 5 h of recovery. These data suggest that increased plasma albumin content contributes to the acute phase of exercise-induced hypervolemia. More importantly, the mechanism by which exercise influences the distribution of albumin between extra- and intravascular stores after exercise is altered by posture and is unknown. We speculate that factors associated with postural changes (e.g., central venous pressure) modify the increase in plasma albumin content and the plasma volume expansion after exercise. (+info)
Physiological variability of fluid-regulation hormones in young women.
We tested the physiological reliability of plasma renin activity (PRA) and plasma concentrations of arginine vasopressin (P[AVP]), aldosterone (P[ALD]), and atrial natriuretic peptide (P[ANP]) in the early follicular phase and midluteal phases over the course of two menstrual cycles (n = 9 women, ages 25 +/- 1 yr). The reliability (Cronbach's alpha >/=0.80) of these hormones within a given phase of the cycle was tested 1) at rest, 2) after 2.5 h of dehydrating exercise, and 3) during a rehydration period. The mean hormone concentrations were similar within both the early follicular and midluteal phase tests; and the mean concentrations of P[ALD] and PRA for the three test conditions were significantly greater during the midluteal compared with the early follicular phase. Although Cronbach's alpha for resting and recovery P[ANP] were high (0.80 and 0.87, respectively), the resting and rehydration values for P[AVP], P[ALD], and PRA were variable between trials for the follicular (alpha from 0.49 to 0.55) and the luteal phase (alpha from 0.25 to 0. 66). Physiological reliability was better after dehydration for P[AVP] and PRA but remained low for P[ALD]. Although resting and recovery P[AVP], P[ALD], and PRA were not consistent within a given menstrual phase, the differences in the concentrations of these hormones between the different menstrual phases far exceeded the variability within the phases, indicating that the low within-phase reliability does not prevent the detection of menstrual phase-related differences in these hormonal variables. (+info)
Endotoxin-induced changes in IGF-I differ in rats provided enteral vs. parenteral nutrition.
The purpose of the present study was to determine whether acute changes in the insulin-like growth factor (IGF) system induced by mild surgical trauma/fasting or endotoxin [lipopolysaccharide (LPS)] are differentially modulated by total enteral nutrition (TEN) or total parenteral nutrition (TPN). Rats had vascular catheters and a gastrostomy tube surgically placed and were fasted overnight. The next morning animals randomly received an isocaloric, isonitrogenous (250 kcal. kg-1. day-1, 1.6 g N. kg-1. day-1) infusion of either TEN or TPN for 48 h. Then rats were injected intravenously with Escherichia coli LPS (1 mg/kg) while nutritional support was continued. Time-matched control animals were injected with saline. After mild surgical trauma and an 18-h fast, TEN was more effective at increasing plasma IGF-I levels than TPN. Subsequent injection of LPS decreased IGF-I in blood, liver, and muscle in both TEN- and TPN-fed rats compared with saline-injected control animals. However, this decrease was approximately 30% greater in rats fed TPN compared with those fed TEN. LPS-induced downregulation of IGF-I mRNA expression in liver and muscle was also more prominent in TPN-fed rats. The LPS-induced increase in plasma corticosterone and tumor necrosis factor-alpha was greater (2- and 1.6-fold, respectively) in TPN-fed rats, and these changes were consistent with the greater reduction in IGF-I seen in these animals. In similarly treated rats allowed to survive for 24 h after LPS injection, the LPS-induced increase in the urinary 3-methylhistidine-to-creatinine ratio was smaller in TEN-fed rats. In summary, LPS reduced systemic levels of IGF-I as well as IGF-I protein and mRNA in critical target organs. Enteral feeding greatly attenuated this response. Maintenance of higher IGF-I levels in TEN-fed rats was associated with a reduction in inflammatory cytokine levels and lower rates of myofibrillar degradation. (+info)
The importance of pyruvate availability to PDC activation and anaplerosis in human skeletal muscle.
No studies have singularly investigated the relationship between pyruvate availability, pyruvate dehydrogenase complex (PDC) activation, and anaplerosis in skeletal muscle. This is surprising given the functional importance attributed to these processes in normal and disease states. We investigated the effects of changing pyruvate availability with dichloroacetate (DCA), epinephrine, and pyruvate infusions on PDC activation and accumulation of acetyl groups and tricarboxylic acid (TCA) cycle intermediates (TCAI) in human muscle. DCA increased resting PDC activity sixfold (P < 0.05) but decreased the muscle TCAI pool (mmol/kg dry muscle) from 1.174 +/- 0.042 to 0.747 +/- 0.055 (P < 0.05). This was probably a result of pyruvate being diverted to acetyl-CoA and acetylcarnitine after near-maximal activation of PDC by DCA. Conversely, neither epinephrine nor pyruvate activated PDC. However, both increased the TCAI pool (1.128 +/- 0.076 to 1.614 +/- 0.188, P < 0.05 and 1.098 +/- 0.059 to 1.385 +/- 0.114, P < 0.05, respectively) by providing a readily available pool of pyruvate for anaplerosis. These data support the hypothesis that TCAI pool expansion is principally a reflection of increased muscle pyruvate availability and, together with our previous work (J. A. Timmons, S. M. Poucher, D. Constantin-Teodosiu, V. Worrall, I. A. Macdonald, and P. L. Greenhaff. J. Clin. Invest. 97: 879-883, 1996), indicate that TCA cycle expansion may be of little functional significance to TCA cycle flux. It would appear therefore that the primary effect of DCA on oxidative ATP provision is to provide a readily available pool of acetyl groups to the TCA cycle at the onset of exercise rather than increasing TCA cycle flux by expanding the TCAI pool. (+info)