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Biomedical subjects

R Dall

Publications and source records attributed to R Dall.

At least 19 recordsLinked to original sources
PubMed2006

The ghrelin response to exercise before and after growth hormone administration.

CONTEXT: We have previously shown that exercise-induced GH release is not mediated by ghrelin, but it remains to be studied whether the increase in GH may suppress postexercise ghrelin levels. OBJECTIVE: The objective of this study was to characterize systemic ghrelin levels after exercise with and without concomitant GH administration. DESIGN, PARTICIPANTS, AND INTERVENTION: Group A: Twenty-nine elite athletes (age, 18-37 yr) were studied after a maximal exercise test. Group B: In a double blind, placebo-controlled, parallel study, 32 healthy subjects (age, 18-33 yr) were randomized to placebo, GH 0.1 IU/kg per day, or GH 0.2 IU/kg per day for 4 wk. These subjects performed a multistage fitness test to assess maximum oxygen uptake at baseline and after 4 wk. We measured total circulating ghrelin levels before and immediately after exercise and at 15, 30, 60, 90, and 120 min after exercise. RESULTS: Group A: Serum ghrelin levels after exercise decreased significantly (P < 0.01). Group B: Exercise at baseline was associated with a significant lowering of ghrelin levels after exercise (P < 0.0001). In addition, 4 wk of high-dose GH were followed by a further approximately 20% reduction in basal and after exercise serum ghrelin (micrograms per liter): 0.78 (range 0.52-1.17) vs. 0.63 (range 0.50-0.91), P < 0.05. CONCLUSIONS: 1) Ghrelin levels decrease significantly after exercise in elite athletes and healthy subjects. 2) High-dose GH suppresses ghrelin levels. 3) These data support the hypothesis that GH feedback inhibits ghrelin secretion.

Adolescent↗
PubMed2005

The effect of submaximal exercise on immuno- and bioassayable IGF-I activity in patients with GH-deficiency and healthy subjects.

OBJECTIVE: Growth hormone (GH) increases during exercise, but the response of the insulin-like growth factor (IGF) system has not been as definitive. Therefore, we investigated the effect of the exercise-induced GH response on the circulating IGF-system in GH-deficient (GHD) and intact adults. DESIGN: Eight GHD adults were studied on 2 occasions, with (+GH) and without (-GH) GH administered (0.4 IU) during exercise (45 min of cycle ergometer exercise at the lactate threshold). Eight age-matched controls were only studied on one occasion. Blood samples were drawn at baseline, during and post-exercise. IGFBP-3 proteolysis was measured by an in vitro proteolytic activity assay, IGF-I bioactivity by novel IGF-I kinase receptor activation assay (KIRA) and other hormones by immunoassay. RESULTS: GH administration to GHD adults resulted in a serum GH peak similar to the exercise-stimulated GH response in GH intact controls, but exercise had only a small impact on the IGF system. IGF-I concentration was lower in controls but was only significantly lower than the +GH day. Neither IGF-I nor -II levels changed over time. IGFBP-1 demonstrated a time effect (P<0.01) in all groups, and a time x group interaction (P<0.01) with a rise at 75 min post-exercise, which was greater in the GHD subjects than controls. IGFBP-2 and -3 increased significantly (P<0.01) over time in the GHD subjects, but not in the controls. No change in IGFBP-3 proteolysis or IGF-I bioactivity was found during exercise or recovery in either group. CONCLUSION: Submaximal exercise induced minor changes in IGFBP-1, -2 and -3, without affecting IGFBP-3 proteolysis and IGF-I bioavailability. Thus the metabolic status during submaximal exercise does not require a change in plasma IGF-I bioavailability. Administration of GH to GHD adults does not result in changes in proteolysis or bioavailability.

Adult↗
PubMed2005

Gender differences in growth hormone response to exercise before and after rhGH administration and the effect of rhGH on the hormone profile of fit normal adults.

OBJECTIVES: Exercise is a potent physiological stimulus of GH secretion. We hypothesized that exogenous recombinant human growth hormone (rhGH) administration through an increase in GH and IGF-I levels would blunt the GH response to exercise. The aim of the study was to examine and compare the impact of rhGH on the exercise-induced GH response in healthy normal men and women. DESIGN AND MEASUREMENTS: Sixty-nine subjects (36 men, 33 women) were randomized to receive low-dose rhGH (0.1 U/kg/day), high dose rhGH (0.2 U/kg/day), or placebo. Subjects were matched for age (24 +/- 3.1), and body mass index (BMI). rhGH was given as a single subcutaneous (s.c.) injection for the first 28 days. All subjects exercised to exhaustion (maximal oxygen consumption--VO2max) before rhGH treatment (Test 1), and on day 28 (Test 2). GH was measured before exercise (time 0), immediately after exercise (time 0') and at 15, 30, 60, 90 and 120 min postexercise. Baseline IGF-I levels were measured before exercise on days 0 and 28. RESULTS: Baseline IGF-I levels showed no gender differences (42.3 women vs. 38.8 nmol/l men) but basal GH values were higher in women (9.9 vs. 1.8 mU/l, P < 0.001). The areas under the GH response curve, for Test 1 were similar in men and women. Peak GH values were higher in women than men (37.9 vs. 23.5 mU/l, but this did not quite reach statistical significance (P = 0.055). In men, administration of rhGH resulted in a significant increase in IGF-I levels over the basal state in both the LD and HD groups (P < 0.0001). In women, the increase in lGF-I levels reached significance only in the HD group (P < 0.0001). On day 28, GH secretion in response to exercise was calculated from the areas under the GH response curve correcting for an exogenous rhGH component (delta AUC). In men, the delta AUC, for Test 2 were similar in all three groups. In women, the delta AUC was higher in the placebo group, than in the HD group (P < 0.02). Free T4 levels decreased significantly in men, and free T3 increased in both men and women, in HD group after the rhGH administration. TSH levels were suppressed only in women. No changes in sex hormones were found in men or women in any of the treatment groups. Conclusions In terms of IGF-I, men are more responsive to rhGH treatment than women. In addition, as men, but not women, were able to overcome the negative feedback control of the elevated IGF-I levels, it seems that exercise may be a more robust stimulus to GH release in men compared to women.

Adult↗
PubMed2004

Epidural anaesthesia with bupivacaine does not cause increased oedema in small gut anatomoses in pigs.

BACKGROUND AND OBJECTIVE: Epidural analgesia is widely used for abdominal surgery due to the properties of 'stress-free' anaesthesia and superior pain control. Nevertheless, sympathomimetics are known to antagonize inflammation. The present study was performed to investigate if epidural local anaesthetics caused increased local oedema formation. METHODS: Thirty Dansk Landrace pigs were randomized into three groups: epidural bupivacaine, epidural morphine or intravenous (i.v.) fentanyl. All animals were anaesthetized with isoflurane and i.v. midazolam and received an identical fluid regimen. Six small bowel resections were performed over a 3-h period and during the following 3 h the anastomoses were resected. Primary end-points were water content in small bowel and mesentery samples before and after gut anastomosis, lymph flow and urine production. RESULTS: The water content in the small bowel samples was not changed by surgery or by the different anaesthetic protocols. In the mesenteric tissue, there was a highly significant increase in water content of the postanastomotic samples compared to pre-anastomotic samples (P < 0.001) and a significant time treatment interaction was revealed (P < 0.05) suggesting an increase in oedema formation in the epidural local anaesthetic group. Lymph flow did not change during the experiments and there were no significant differences between the groups (P = 0.80). The mean total urine output was 44% higher in the epidural morphine group compared to the local anaesthetic group (P = 0.17). CONCLUSIONS: Surgery did not increase gut wall water content, but acute oedema formation resulted in the peri-resectional mesenterial tissue, more prominently so in the bupivacaine group.

Analgesics, Opioid↗
PubMed2003

The growth hormone/insulin-like growth factor-I axis hormones and bone markers in elite athletes in response to a maximum exercise test.

The aim of the GH-2000 project is to develop a method for detecting GH doping among athletes. Previous papers in the GH-2000 project have proposed that a forthcoming method to detect GH doping will need specific components from the GH/IGF-I axis and bone markers because these specific variables seem more sensitive to exogenous GH than to exercise. The present study examined the responses of the serum concentrations of these specific variables to a maximum exercise test in elite athletes from selected sports. A total of 117 elite athletes (84 males and 33 females; mean age, 25 yr; range, 18-53 yr) from Denmark, the United Kingdom, Italy, and Sweden participated in the study. The serum concentrations of total GH, GH22 kDa, IGF-I, IGF binding protein (IGFBP)-2, IGFBP-3, acid-labile subunit, procollagen type III (P-III-P), and the bone markers osteocalcin, carboxy-terminal cross-linked telopeptide of type I collagen (ICTP), and carboxy-terminal propeptide of type I procollagen were measured. The maximum exercise test showed, in both genders, a peak concentration of total GH (P < 0.001) and GH22 kDa (P < 0.001) by the time exercise ended compared with baseline, and a subsequent decrease to baseline levels within 30-60 min after exercise. The mean time to peak value for total GH and GH22 kDa was significantly shorter in males than females (P < 0.001). The components of the IGF-I axis showed a similar pattern, with a peak value after exercise compared with baseline for IGF-I (P < 0.001, males and females); IGFBP-3 (P < 0.001, males and females); acid-labile subunit [P < 0.001, males; not significant (NS), females], and IGFBP-2 (P < 0.05, females; NS, males). The serum concentrations of the bone markers ICTP (P < 0.001, males; P < 0.05, females) and P-III-P (P < 0.001, males and females) increased in both genders, with a peak value in the direct post-exercise phase and a subsequent decrease to baseline levels or below within 120 min. The osteocalcin and propeptide of type I procollagen values did not change during the exercise test. Specific reference ranges for each variable in the GH/IGF-I axis and bone markers at specific time points are presented. Most of the variables correlated negatively with age. In summary, the maximum exercise test showed a rather uniform pattern, with peak concentrations of the GH/IGF-I axis hormones and the bone markers ICTP and P-III-P immediately after exercise, followed by a subsequent decrease to baseline levels. The time to peak value for total GH and GH22 kDa was significantly shorter for females compared with males. This paper presents reference ranges for each marker in each gender at specific time points in connection to a maximum exercise test to be used in the development of a test for detection of GH abuse in sports.

Adult↗
PubMed2002

Glucocorticoid induced insulin resistance impairs basal but not glucose entrained high-frequency insulin pulsatility in humans.

AIMS/HYPOTHESIS: Type II (non-insulin-dependent) diabetes mellitus is characterized by abnormal insulin secretion, which involves a disrupted basal and glucose-entrained insulin pulsatility, and by insulin resistance. The aim of this study was to examine the influence of glucocorticoid-mediated insulin resistance on the regularity of high frequency insulin pulsatility. METHODS: Eight healthy men (means +/- SD; age 24.4 +/- 0.5 years, BMI 23.2 +/- 0.7 kg/m2) were examined after prednisolone treatment (30 mg/day) or placebo for 6 days in a double-blind, placebo controlled, cross-over study with a 6-week washout period. Blood was collected every minute for 60 min during baseline and glucose-entrainment. Time-series were assessed by spectral and autocorrelation analyses and a first-phase insulin secretion test was carried out. RESULTS: Prednisolone treatment led to insulin resistance as expected (HOMA-S; prednisolone vs placebo; 1.85 +/- 0.26 vs 1.02 +/- 0.10; p < 0.01) with exaggerated first-phase insulin secretion (3016 +/- 468 pmol/l vs 1688 +/- 207 pmol/l; p < 0.01), suggesting a stable disposition index. During baseline, normalized spectral power of serum insulin concentration time-series was reduced during prednisolone exposure compared with placebo (8.40 +/- 0.95 vs 11.79 +/- 1.66; p < 0.05) indicating a disturbed high-frequency oscillatory insulin release. A similar trend was observed using autocorrelation analysis (0.23 +/- 0.04 vs 0.32 +/- 0.07; p = 0.12). During glucose entrainment no difference in normalized spectral power or in the autocorrelation coefficient between prednisolone and placebo (p > 0.1) was observed. CONCLUSION/INTERPRETATION: Six days of prednisolone treatment resulted in a pertubed high-frequency insulin release in the fasting state whereas the ability of glucose to entrain insulin secretion was preserved. This indicates a mechanism of pertubed glucose-insulin feedback mechanism which causes irregular oscillatory insulin release.

Adult↗
PubMed2001

Determination of free insulin-like growth factor-I in human serum: comparison of ultrafiltration and direct immunoradiometric assay.

Two fundamentally different methods are currently used for the determination of free insulin-like growth factor-I (IGF-I): ultrafiltration by centrifugation (UF) and direct immunoradiometric assay (IRMA). The aim was to evaluate a commercial IRMA (DSL, Webster, TX, USA) and to compare it with UF. In the IRMA it is recommended that samples be incubated for 2 h at 5;C. When comparing samples (n = 8) incubated for 1 and 2 h, levels increased by 27 +/- 5% (P< 0.0001). When incubating samples at 22;C instead of 5;C, levels increased by 192 +/- 32% (P< 0.0001). Addition of IGF-binding protein-1 (IGFBP-1) to normal sera (n = 6) dose-dependently decreased ultrafiltered free IGF-I only (P< 0.0007). Similarly, UF was more sensitive than IRMA to addition of IGFBP-2 (P< 0.05). In healthy subjects (n = 35) IRMA yielded 20% higher levels than UF (1.09 +/- 0.09 vs 0.91 +/- 0.12 microg/L; P< 0.0001). IRMA and UF yielded similar results in healthy subjects treated with IGF-I (n = 5) or growth hormone (n = 7) and in acromegalic patients (n = 6) before and after somatostatin analogue treatment. However, marked differences were observed in conditions with elevated IGFBP-1 and -2. In type-1 diabetics (n = 23) ultrafiltered free IGF-I was more reduced than IRMA free IGF-I (38 +/- 9 vs 76 +/- 7% of matched controls (n = 13); P< 0.0001). In patients with chronic renal failure (n = 25), IRMA free IGF-I was identical to control levels (n = 13), whereas ultrafiltered free IGF-I was decreased by 51 +/- 7% (P< 0.0001). Similarly, women with anorexia nervosa (n = 9) studied before and after weight gain showed significant changes in ultrafiltered free IGF-I only (P< 0.03). In conclusion, IRMA was not very robust with respect to variations in sample incubation and this may bias results. IRMA generally yielded higher levels than UF, in accordance with the knowledge that IRMA measures free plus readily dissociable IGF-I. IRMA was less affected than UF by added IGFBP-1 and -2, and reductions in free IGF-I were better revealed by UF than IRMA.

Acromegaly↗
PubMed2001

Effects of growth hormone on renal tubular handling of sodium in healthy humans.

To investigate the mechanisms behind the water- and sodium-retaining effects of growth hormone (GH), we studied the effect of GH on 1) water and sodium homeostasis, 2) the renin-angiotensin-aldosterone system (RAAS), and 3) lithium clearance (C(Li)) with and without concomitant prostaglandin (PG) synthesis inhibition with ibuprofen. GH administration for 6 days induced a significant increase in plasma renin, which was abolished by coadministration of ibuprofen (mU x l(-1) x 24 h(-1): control: 22.4 +/- 4.3; GH: 37.7 +/- 8.8; ibuprofen: 15.2 +/- 3.0; GH + ibuprofen: 19.7 +/- 2.5; ANOVA: P < 0.01). Comparable increments in extracellular volume were seen after 6-day treatment with GH alone and in combination with ibuprofen [liters: control, 19.57 +/- 0.92; GH, 20.80 +/- 1.00 (ANOVA: P < 0.0005); ibuprofen, 19.38 +/- 0.90; GH + ibuprofen, 21.63 +/- 1.37 (ANOVA: P < 0.0005)]. Treatment with GH increased C(Li) and changed the tubular handling of sodium and water. The absolute distal sodium reabsorption was increased, and this was only partially counterbalanced by decreased reabsorption in the proximal tubules. The data demonstrate that GH-induced activation of the RAAS can be blocked by concomitant PG synthesis inhibition and that the tubular effects of GH include increased distal nephron sodium and water reabsorption.

Adult↗
PubMed2001

No influence of prednisolone on IGFBP-3 proteolysis in healthy young men.

AIMS: The impact of growth hormone (GH) and prednisolone on the GH/insulin-like growth factor (IGF) axis with special emphasis on IGF binding protein-3 (IGFBP-3) proteolysis was studied in 8 healthy adults in a double-blind cross-over study with four periods: (1) placebo; (2) s.c. GH 0.1 IU/kg/day; (3) oral prednisolone 50 mg/day, and (4) co-administration of GH and prednisolone. METHODS: Each treatment period lasted for 4 days followed by a washout period of 10 days. We measured IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 by immunoassays, IGFBP-3 by Western ligand blotting (WLB) and finally in vitro IGFBP-3 proteolysis by a (125)I-IGFBP-3 degradation assay. RESULTS: IGF-I levels increased by 99% during GH administration and 67% during co-administration of GH and prednisolone (p < 0.0005), whereas no significant change was seen during prednisolone alone. IGFBP-1 levels decreased 55% during the prednisolone period (p < 0.002), but the between period changes were not significant (p < 0.1). IGFBP-2 decreased 33% during co-administration of GH and prednisolone (p < 0.002). IGFBP-3 increased 12% during GH and 7% during co-administration of GH and prednisolone (p < 0.003 and p < 0.03 compared to placebo, respectively), whereas prednisolone alone induced no significant changes. IGFBP-3 measured by WLB did not change significantly, neither did IGFBP-3 proteolysis. CONCLUSIONS: Prednisolone administration induces only minimal changes in circulating components of the IGF axis and is not accompanied by alterations in IGFBP-3 proteolysis. This indicates that the metabolic effects of glucocorticoids do not depend on serum IGF-I.

Adult↗
PubMed2001

The response of molecular isoforms of growth hormone to acute exercise in trained adult males.

Circulating GH consists of multiple molecular isoforms, all derived from the one gene in nonpregnant humans. To assess the effect of a potent stimulus to pituitary secretion on GH isoforms, we studied 17 aerobically trained males (age, 26.9 +/- 1.5 yr) in a randomized, repeat measures study of rest vs. exercise. Exercise consisted of continuous cycle ergometry at approximately 80% of predetermined maximal oxygen uptake for 20 min. Serum was assayed for total, pituitary, 22-kDa, recombinant, non-22-kDa, 20-kDa, and immunofunctional GH. All isoforms increased during, peaked at the end, and declined after exercise. At peak exercise, 22-kDa GH was the predominant isoform. After exercise, the ratios of non-22 kDa/total GH and 20-kDa GH/total GH increased and those of recombinant/pituitary GH decreased. The disappearance half-times for pituitary GH and 20-kDa GH were significantly longer than those for all other isoforms. We conclude that 1) all molecular isoforms of GH measured increased with and peaked at the end of acute exercise, with 22-kDa GH constituting the major isoform in serum during exercise; and 2) the proportion of non-22-kDa isoforms increased after exercise due in part to slower disappearance rates of 20-kDa and perhaps other non-22-kDa GH isoforms. It remains to be determined whether the various biological actions of different GH isoforms impact on postexercise homeostasis.

Adult↗
PubMed2001

GH strongly affects serum concentrations of mannan-binding lectin: evidence for a new IGF-I independent immunomodulatory effect of GH.

Studies in animals and humans indicate that GH and IGF-I modulate immune function. Recently, it was reported that GH therapy increased the mortality in critically ill patients. The excessive mortality was almost entirely attributable to septic shock or multiorgan failure, suggesting that a GH-induced modulation of immune function was involved. In the present study, we examined whether GH or IGF-I influences the serum concentrations of mannan-binding lectin (MBL). MBL is a plasma protein of the innate immune system that initiates the complement cascade and activates inflammation after binding to carbohydrate structures on microbial surfaces. We performed a cross-over study of 16 healthy men examined during a control period, and during treatment with either GH or IGF-I for 6 d. The levels of MBL were more than doubled during GH treatment, whereas no changes were observed in the IGF-I group or during the control period (P < 0.001). IGF-I levels were elevated similarly during treatment with GH and IGF-I. Subsequently, we studied 30 healthy persons and 25 GH-deficient (GHD) patients randomized to treatment with GH or placebo in a double-blinded manner, and further included samples from 23 patients with active acromegaly examined before and after treatment with octreotide or the GH-receptor antagonist pegvisomant for 3 months. Baseline concentrations of MBL were lower in GHD patients and higher in acromegalic patients than in healthy subjects (P < 0.02). Treatment with GH doubled the MBL concentrations in healthy subjects and almost quadrupled the concentrations in GHD patients; whereas in acromegalic patients, the levels of MBL were reduced to approximately two thirds of the initial values during treatment with octreotide or pegvisomant. Our results demonstrate that treatment with GH, but not IGF-I, significantly increases MBL concentrations. The clinical consequences of this new link between the endocrine and the immune system remain to be elucidated.

Acromegaly↗
PubMed2001

No evidence of insulin-like growth factor-binding protein 3 proteolysis during a maximal exercise test in elite athletes.

The aim of the present study was to examine the GH/insulin-like growth factor (IGF) axis, post exercise, with emphasis on IGF-binding protein (IGFBP)-3 proteolysis. Sixteen elite rowers (8 female/8 male) performed a stepwise submaximal rowing test followed by a 6- to 7-min-long maximal test. Blood samples were drawn at baseline, t = 0 (end of exercise) and t = 15, 30, 60, 90, and 120 min. GH and IGFBP-1 levels increased post exercise (P < 0.0005). Total IGF-I and IGF-II increased significantly post exercise (P < 0.0005) but not after albumin correction. Free IGF-I decreased after exercise with nadir coincidently with the IGFBP-1 peak, and free IGF-II decreased post exercise coincidently with the IGFBP-6 peak. IGFBP-3, measured by immunoradiometric assay, increased after exercise (P < 0.0005) but not after albumin adjustment. IGFBP-3 proteolysis (%) (measured by a specific in vitro proteolytic activity assay) and IGFBP-3 (measured by Western ligand blotting) were unchanged post exercise. Albumin-adjusted levels of IGFBP-6 increased by 18% (P < 0.0005), whereas IGFBP-2 and IGFBP-4 did not change significantly post exercise. Our findings do not support the hypothesis that short-term strenuous exercise induces major acute changes in the GH/IGF axis. To what degree the protein anabolic effects of regular exercise are associated with acute alterations in the GH/IGF axis remains unclear.

Adult↗
PubMed2001

Changes in non-22-kilodalton (kDa) isoforms of growth hormone (GH) after administration of 22-kDa recombinant human GH in trained adult males.

GH is being used by elite athletes to enhance sporting performance. To examine the hypothesis that exogenous 22-kDa recombinant human GH (rhGH) administration could be detected through suppression of non-22-kDa isoforms of GH, we studied seventeen aerobically trained males (age, 26.9 +/- 1.5 yr) randomized to rhGH or placebo treatment (0.15 IU/kg/day for 1 week). Subjects were studied at rest and in response to exercise (cycle-ergometry at 65% of maximal work capacity for 20 min). Serum was assayed for total GH (Pharmacia IRMA and pituitary GH), 22-kDa GH (2 different 2-site monoclonal immunoassays), non-22-kDa GH (22-kDa GH-exclusion assay), 20-kDa GH, and immunofunctional GH. In the study, 3 h after the last dose of rhGH, total and 22-kDa GH concentrations were elevated, reflecting exogenous 22-kDa GH. Non-22-kDa and 20-kDa GH levels were suppressed. Regression of non-22-kDa or 20-kDa GH against total or 22-kDa GH produced clear separation of treatment groups. In identical exercise studies repeated between 24 and 96 h after cessation of treatment, the magnitude of the responses of all GH isoforms was suppressed (P < 0.01), but the relative proportions were similar to those before treatment. We conclude: 1) supraphysiological doses of rhGH in trained adult males suppressed exercise-stimulated endogenous circulating isoforms of GH for up to 4 days; 2) the clearest separation of treatment groups required the simultaneous presence of high exogenous 22-kDa GH and suppressed 20-kDa or non-22-kDa GH concentrations; and 3) these methods may prove useful in detecting rhGH abuse in athletes.

Adult↗
PubMed2000

The effect of four weeks of supraphysiological growth hormone administration on the insulin-like growth factor axis in women and men. GH-2000 Study Group.

Measurements of serum insulin-like growth factor I (IGF-I) and related markers are routinely used in the diagnosis and treatment of GH deficiency and excess. The validity of these markers for assessment of exogenous GH exposure in healthy adults is, however, unknown. We therefore conducted a double blind, placebo-controlled GH treatment trial in 99 healthy subjects [49 women and 50 men; mean +/- SE age, 25.6+/-0.6 (women)/25.7+/-0.6 yr (men)]. Blood was collected weekly during a 4-week treatment period (days 1-28), and the subjects were subsequently followed for additional 8 weeks (days 29-84). The treatment arms included: I) 0.1 IU/kg x day GH (n = 30; GH 0.1), II) 0.2 IU/kg x day GH (n = 29; GH 0.2), and III) placebo (n = 40). At baseline no gender-specific differences existed, except that the acid-labile subunit (ALS) levels were higher in females. Serum insulin-like growth factor I (IGF-I) levels in males receiving GH increased significantly through day 42 with no significant difference between the 2 doses. The absolute IGF-I response was significantly lower in females, and there was a clear dose-response relationship. ALS levels in males increased through day 30 (P < 0.001). In females ALS levels were only modestly increased on day 28 compared with those in the placebo group (P < 0.02). IGF-binding protein-3 (IGFBP-3) levels in males increased significantly in the GH 0.1 and the GH 0.2 groups on day 30 (P < 0.03), whereas no solid IGFBP-3 increase was detected in females. IGFBP-2 levels decreased insignificantly during GH exposure in both genders. A gender-specific upper normal range for each analyte was arbitrarily defined as 4 SD above the mean level at baseline. On the basis of IGF-I levels alone, GH exposure in the GH 0.2 group was detected in 86% of the males and in 50% of the females on day 21. On day 42 GH exposure was only weakly detectable in males and was not detectable in females. We conclude that 1) males are significantly more responsive than females to exogenous GH; 2) the increase in IGF-I is more robust compared with those in IGFBP-3 and ALS; 3) IGFBP-2 changes very little during GH treatment; and 4) among IGF-related substances, IGF-I is the most specific marker of supraphysiological GH exposure.

Adolescent↗
PubMed2000

Growth hormone (GH) effects on bone and collagen turnover in healthy adults and its potential as a marker of GH abuse in sports: a double blind, placebo-controlled study. The GH-2000 Study Group.

The effects of GH on bone remodeling in healthy adults have not been systematically investigated. An analysis of these effects might provide insights into GH physiology and might yield data useful for the detection of GH doping in sports. The aim of this study was to evaluate the effects of GH administration on biochemical markers of bone and collagen turnover in healthy volunteers. Ninety-nine healthy volunteers of both sexes were enrolled in a multicenter, randomized, double blind, placebo-controlled study and assigned to receive either placebo (40 subjects) or recombinant human GH (0.1 IU/kg day in 29 subjects and 0.2 IU/kg x day in 30 subjects). The treatment duration was 28 days, followed by a 56-day wash-out period. The biochemical markers evaluated were the bone formation markers osteocalcin and C-terminal propeptide of type I procollagen, the resorption marker type I collagen telopeptide, and the soft tissue marker procollagen type III. All variables increased on days 21 and 28 in the two active treatment groups vs. levels in both the baseline (P < 0.01) and placebo (P < 0.01) groups. The increment was more pronounced in the 0.2 IU/kg-day group and remained significant on day 84 for procollagen type III (from 0.53 +/- 0.13 to 0.61 +/- 0.14 kU/L; P < 0.02) and osteocalcin (from 12.2 + 2.9 to 14.6 +/- 3.6 UG/L; P < 0.02), whereas levels of C-terminal propeptide of type I procollagen and type I collagen telopeptide declined after day 42 and were no longer significantly above baseline on day 84 (from 3.9 +/- 1.2 to 5.1 +/-1.5 microg/L and from 174 +/- 60 to 173 +/- 53 microg/L, respectively). Gender-related differences were observed in the study; females were less responsive than males to GH administration with respect to procollagen type III and type I collagen telopeptide (P < 0.001). In conclusion, exogenous GH administration affects the biochemical parameters of bone and collagen turnover in a dose- and gender-dependent manner. As GH-induced modifications of most markers, in particular procollagen type III and osteocalcin, persist after GH withdrawal, they may be suitable markers for detecting GH abuse.

Adult↗
PubMed1999

Responses of the growth hormone (GH) and insulin-like growth factor axis to exercise, GH administration, and GH withdrawal in trained adult males: a potential test for GH abuse in sport.

GH abuse by elite athletes is currently undetectable. To define suitable markers of GH doping, we assessed the effects of acute exercise, GH administration, and GH withdrawal on the GH/insulin-like growth factor (IGF) axis in athletic adult males. Acute endurance-type exercise increased serum GH, GH-binding protein (GHBP), total IGF-I, IGF-binding protein (IGFBP)-3, and acid-labile subunit (ALS), each peaking at the end of exercise. IGFBP-1 increased after exercise was completed. Free IGF-I did not change with exercise. Recombinant human GH treatment (0.15 IU/kg x day) for 1 week increased serum total IGF-I, IGFBP-3, and ALS, exaggerating the responses to exercise. IGFBP-2 and IGFBP-1 were trivially suppressed. After GH withdrawal, the GH response to identical exercise was suppressed. Total IGF-I, IGFBP-3, and ALS returned to baseline over 3-4 days. In summary, 1) acute exercise transiently increased all components of the IGF-I ternary complex, possibly due to mobilization of preformed intact complexes; 2) GH pretreatment augmented the exercise-induced changes in ternary complexes; 3) postexercise IGFBP-1 increments may protect against delayed onset hypoglycemia; 4) serum total IGF-I, IGFBP-3, and ALS may be suitable markers of GH abuse; and 5) differences in disappearance times altered the sensitivity of each marker for detecting GH abuse.

Adult↗
PubMed1998

Resting metabolic rate in healthy adults: relation to growth hormone status and leptin levels.

Studies in patients with acromegaly and growth hormone (GH) deficiency, and administration of GH in normal and obese subjects and in patients with GH deficiency, suggest that GH increases resting metabolic rate (RMR) independently of changes in body composition. To test whether endogenous GH status determines RMR, we studied 38 healthy adults (18 women and 18 men) in two age groups (young, 30+/-0 years (n=18); older, 51+/-1 years [n=18]) with indirect calorimetry, deconvolution analysis of 24-hour GH secretion, arginin stimulation test, insulin-like growth factor-I (IGF-I) measurement, lean and fat tissue distribution (computed tomography [CT] and dual-energy x-ray absorptiometry), assessment of physical fitness (maximal oxygen consumption [VO2max]), thyroid status, and serum leptin levels. RMR was higher in men compared with women, whereas RMR per lean body mass (LBM) (kcal x 24 h(-1) x kg(-1)) was higher in women (30.0+/-0.5 v 33.0 2/3 0.8; P=.003). GH secretion was higher in women and in young people. Total-body fat (TBF) was higher in women, whereas LBM and abdominal fat were higher in men. Older people had significantly more TBF and abdominal fat as compared with younger people. VO2max was higher in younger people. Leptin levels were higher in women and in older people. Thyroid status was narrowly within the normal range in all subjects. RMR was strongly correlated with LBM (r=.90, P < .001). RMR/LBM correlated strongly with TBF (r=.49, P < .01) and leptin (r=.56, P < .001), but not with GH status. By multiple regression analysis, sex and TBF were the strongest predictors of RMR/LBM. However, in the young subgroup, GH production rate was a positive determinant of RMR/LBM. In the male subgroup, leptin was a stronger predictor than TBF of RMR/LBM (P < .001). Neither age, physical fitness, nor thyroid status contributed independently to predict RMR/LBM. In conclusion, (1) LBM was the most important determinant of RMR; (2) RMR/LBM was higher in women and depended strongly on TBF; (3) GH status in healthy adults was only weakly associated with RMR; and (4) in men, serum leptin levels were a strong positive determinant of RMR.

Adult↗