Whole-body leucine turnover in adults on conventional treatment for hypopituitarism

1993 ◽  
Vol 129 (2) ◽  
pp. 158-164 ◽  
Author(s):  
Salem A Beshyah ◽  
Patrick S Sharp ◽  
Susan V Gelding ◽  
David Halliday ◽  
Desmond G Johnston
Keyword(s):  
Growth Hormone ◽  
Serum Insulin ◽  
Hormone Replacement ◽  
Whole Body ◽  
Leucine Incorporation ◽  
Gh Treatment ◽  
Mean Values ◽  
Growth Hormone Replacement Therapy ◽  
Igf I ◽  
Normal Controls

This study has investigated protein metabolism in adults with hypopituitarism before and after growth hormone (GH) replacement and in matched controls. Whole-body leucine turnover was measured in 16 GH-deficient adult hypopituitary patients (nine females and seven males) on standard thyroid, adrenal and sex hormone replacement and in 20 normal controls using primed continuous infusion of l-[1 – 13C]leucine. In seven of the patients, leucine turnover was restudied following 6 months' treatment with biosynthetic human GH (0.025–0.05 IU/kg body wt daily, with the final dose determined by patient tolerance). Compared with normal controls, hypopituitary patients had significantly reduced leucine flux (mean±sd: 97.8±24.9 vs 131.0±23.0 μmol·h−1·kg−1; p<0.001), reduced leucine incorporation into protein (80.4±20.9 vs 108.8±19.6 μmol·h−1·kg−1; p<0.001) and reduced leucine oxidation (17.4±4.8 vs 22.2±8.1 μmol·h−1·kg−1; p<0.05). Leucine turnover was similar in male and female patients. In the patients, leucine flux correlated positively with body weight (p = 0.51, p<0.05) and leucine incorporation in protein correlated positively with lean body mass (p = 0.55, p <0.05) and in male patients leucine flux correlated positively with serum insulin-like growth factor I (IGF-I) levels (ρ=0.71, p<0.05). No significant relationship was observed with age or duration of hypopituitarism. Growth hormone replacement therapy did not produce a uniform effect on leucine metabolism. Mean values of leucine flux, oxidation and incorporation into protein increased, although the differences were not statistically significant. The patients on higher GH doses and with a higher serum IGF-I response were those who demonstrated an increase in leucine turnover. We conclude that leucine turnover in hypopituitary adults is reduced compared with normal controls. The effect of GH treatment for 6 months at conventional doses in hypopituitary adults is not uniform and may be dose-dependent.

Regulation of whole body energy homeostasis with growth hormone replacement therapy and endurance exercise

2011 ◽  
Vol 43 (12) ◽  
pp. 739-748 ◽  
Author(s):  
Robert Oosterhof ◽  
Michael Ith ◽  
Roman Trepp ◽  
Emanuel Christ ◽  
Martin Flück
Keyword(s):  
Growth Hormone ◽  
Hormone Replacement Therapy ◽  
Lipid Metabolism ◽  
Tibialis Anterior ◽  
Hormone Replacement ◽  
Whole Body ◽  
Growth Hormone Replacement ◽  
Muscle Lipid ◽  
Growth Hormone Replacement Therapy ◽  
Metabolic Fitness

We hypothesized that network analysis is useful to expose coordination between whole body and myocellular levels of energy metabolism and can identify entities that underlie skeletal muscle's contribution to growth hormone-stimulated lipid handling and metabolic fitness. We assessed 112 metabolic parameters characterizing metabolic rate and substrate handling in tibialis anterior muscle and vascular compartment at rest, after a meal and exercise with growth hormone replacement therapy (GH-RT) of hypopituitary patients ( n = 11). The topology of linear relationships (| r | ≥ 0.7, P ≤ 0.01) and mutual dependencies exposed the organization of metabolic relationships in three entities reflecting basal and exercise-induced metabolic rate, triglyceride handling, and substrate utilization in the pre- and postprandial state, respectively. GH-RT improved aerobic performance (+5%), lean-to-fat mass (+19%), and muscle area of tibialis anterior (+2%) but did not alter its mitochondrial and capillary content. Concomitantly, connectivity was established between myocellular parameters of mitochondrial lipid metabolism and meal-induced triglyceride handling in serum. This was mediated via the recruitment of transcripts of muscle lipid mobilization (LIPE, FABP3, and FABP4) and fatty acid-sensitive transcription factors (PPARA, PPARG) to the metabolic network. The interdependence of gene regulatory elements of muscle lipid metabolism reflected the norm in healthy subjects ( n = 12) and distinguished the regulation of the mitochondrial respiration factor COX1 by GH and endurance exercise. Our observations validate the use of network analysis for systems medicine and highlight the notion that an improved stochiometry between muscle and whole body lipid metabolism, rather than alterations of single bottlenecks, contributes to GH-driven elevations in metabolic fitness.

Growth hormone and testosterone interact positively to enhance protein and energy metabolism in hypopituitary men

2005 ◽  
Vol 289 (2) ◽  
pp. E266-E271 ◽  
Author(s):  
James Gibney ◽  
Troels Wolthers ◽  
Gudmundur Johannsson ◽  
A. Margot Umpleby ◽  
Ken K. Y. Ho
Keyword(s):  
Growth Hormone ◽  
Protein Metabolism ◽  
Resting Energy Expenditure ◽  
Whole Body ◽  
Combined Treatments ◽  
Gh Treatment ◽  
Additional Increase ◽  
Body Protein ◽  
Igf I ◽  
The Impact

We investigated the impact of growth hormone (GH) alone, testosterone (T) alone, and combined GH and T on whole body protein metabolism. Twelve hypopituitary men participated in two studies. Study 1 compared the effects of GH alone with GH plus T, and study 2 compared the effects of T alone with GH plus T. IGF-I, resting energy expenditure (REE), and fat oxidation (Fox) and rates of whole body leucine appearance (Ra), oxidation (Lox), and nonoxidative leucine disposal (NOLD) were measured. In study 1, GH treatment increased mean plasma IGF-I ( P < 0.001). GH did not change leucine Ra but reduced Lox ( P < 0.02) and increased NOLD ( P < 0.02). Addition of T resulted in an additional increase in IGF-I ( P < 0.05), reduction in Lox ( P < 0.002), and increase in NOLD ( P < 0.002). In study 2, T alone did not alter IGF-I levels. T alone did not change leucine Ra but reduced Lox ( P < 0.01) and increased NOLD ( P < 0.01). Addition of GH further reduced Lox ( P < 0.05) and increased NOLD ( P < 0.05). In both studies, combined treatments on REE and Fox were greater than either alone. In summary, GH-induced increase of circulating IGF-I is augmented by T, which does not increase IGF-I in the absence of GH. T and GH exerted independent and additive effects on protein metabolism, Fox and REE. The anabolic effects of T are independent of circulating IGF-I.

Bioavailability and bioactivity of three different doses of nasal growth hormone (GH) administered to GH-deficient patients: comparison with intravenous and subcutaneous administration

1996 ◽  
Vol 135 (3) ◽  
pp. 309-315 ◽  
Author(s):  
Torben Laursen ◽  
Birgitte Grandjean ◽  
Jens OL Jørgensen ◽  
Jens S Christiansen
Keyword(s):  
Growth Hormone ◽  
Metabolic Response ◽  
Serum Insulin ◽  
Subcutaneous Administration ◽  
Absolute Bioavailability ◽  
High Dose ◽  
Gh Treatment ◽  
Significant Difference ◽  
Igf I ◽  
Different Doses

Laursen T, Grandjean B, Jørgensen JOL, Christiansen JS. Bioavailability and bioactivity of three different doses of nasal growth hormone (GH) administered to GH-deflcient patients: comparison with intravenous and subcutaneous administration. Eur J Endocrinol 1996;135:309–15. ISSN 0804–4643 The current mode of growth hormone (GH) replacement therapy is daily subcutaneous (sc) injections given in the evening. This schedule is unable to mimic the endogenous pulsatile pattern of GH secretion, which might be of importance for the induction of growth and other GH actions. The present study was conducted in order to study the pharmacokinetics of different doses of GH following intranasal (IN) administration and the biological activity of GH after IN administration as compared with sc and intravenous (iv) delivery. Sixteen GH-deficient patients were studied on five different occasions. On three occasions GH was administered intranasally in doses of 0.05, 0.10 and 0.20IU/kg, using didecanoyl-l-α-phosphatidylcholine as an enhancer. On the other two occasions the patients received an sc injection (0.10IU/kg) and an iv injection (0.015IU/kg) of GH, respectively. The nasal doses and the sc injection were given in random order in a crossover design. In a double-blinded manner the subjects received the three nasal doses as one puff in each nostril. The patients received no GH treatment between the five studies or during the last week before the start of each study. Intravenous administration produced a short-lived serum GH peak value of 128.12 ± 6.71 μg/l. Peak levels were 13.98±1.63 μg/l after sc injection and 3.26±0.38. 7.07±0.80 and 8.37± 1.31 μg/l, respectively, after the three nasal doses. The peak values of the 0.05 and the 0.20IU/kg nasal doses were significantly different (p = 0.007). The mean levels obtained by the low nasal dose were significantly lower than those obtained with the medium (p < 0.001) and the high dose (p < 0.001). while there was no significant difference between the medium and the high doses. The absolute bioavailability of GH following sc relative to iv administration was 49.5%. The bioavailabilities of the nasal doses were: 7.8% (0.05 IU), 8.9% (0.10 IU) and 3.8% (0.20 IU). Serum insulin-like growth factor I (IGF-I) levels increased significantly after sc administration only. Mean levels were significantly higher after sc administration as compared with the iv and all three nasal does (p < 0.001). Serum IGF binding protein 3 (IGFBP-3) levels remained unchanged on all five occasions. Mean serum IGFBP-1 levels were significantly lower after sc GH injection than after administration of the iv (p < 0.001) and the three nasal doses (p < 0.005). Subcutaneous GH administration resulted in significantly higher levels of serum insulin and blood glucose (p < 0.001). In conclusion, the bioavailability of nasal GH was low (3.8–8.9%). An iv bolus injection of, on average, 1 IU of GH induced no metabolic response. Only sc GH administration induced increased levels of IGF-I, insulin and glucose. These data reveal that a closer imitation of the physiological GH pulses than achieved by sc GH administration is of limited importance for the induction of a metabolic response to GH. Torben Laursen, Medical Department M (Diabetes & Endocrinology), Aarhus Kommunehospital, DK-8000 Aarhus C. Denmark

scholarly journals THERAPY OF ENDOCRINE DISEASE: Growth hormone replacement therapy in adults: 30 years of personal clinical experience

2018 ◽  
Vol 179 (1) ◽  
pp. R47-R56 ◽  
Author(s):  
Jens O L Jørgensen ◽  
Anders Juul
Keyword(s):  
Growth Hormone ◽  
Hormone Replacement ◽  
Human Growth ◽  
Elderly Subjects ◽  
Dose Requirement ◽  
Gh Treatment ◽  
Growth Hormone Replacement Therapy ◽  
Gh Replacement ◽  
Excess Morbidity ◽  
Aerobic Exercise Capacity

The acute metabolic actions of purified human growth hormone (GH) were first documented in adult hypopituitary patients more than 50 years ago, and placebo-controlled long-term GH trials in GH-deficient adults (GHDA) surfaced in 1989 with the availability of biosynthetic human GH. Untreated GHDA is associated with excess morbidity and mortality from cardiovascular disease and the phenotype includes fatigue, reduced aerobic exercise capacity, abdominal obesity, reduced lean body mass, osteopenia and elevated levels of circulating cardiovascular biomarkers. Several of these features reverse and normalize with GH replacement. It remains controversial whether quality of life, assessed by questionnaires, improves. The known side effects are fluid retention and insulin resistance, which are reversible and dose dependent. The dose requirement declines markedly with age and is higher in women. Continuation of GH replacement into adulthood in patients with childhood-onset disease is indicated, if the diagnosis is reconfirmed. GH treatment of frail elderly subjects without documented pituitary disease remains unwarranted. Observational data show that mortality in GH-replaced patients is reduced compared to untreated patients. Even though this reduced mortality could be due to selection bias, GH replacement in GHDA has proven beneficial and safe.

scholarly journals Growth hormone regulation of metabolic gene expression in muscle: a microarray study in hypopituitary men

2007 ◽  
Vol 293 (1) ◽  
pp. E364-E371 ◽  
Author(s):  
Klara Sjögren ◽  
Kin-Chuen Leung ◽  
Warren Kaplan ◽  
Margaret Gardiner-Garden ◽  
James Gibney ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Hormone ◽  
Lipid Oxidation ◽  
Expression Profiles ◽  
Whole Body ◽  
Circadian Gene ◽  
Gh Treatment ◽  
Substrate Metabolism ◽  
Igf I

Muscle is a target of growth hormone (GH) action and a major contributor to whole body metabolism. Little is known about how GH regulates metabolic processes in muscle or the extent to which muscle contributes to changes in whole body substrate metabolism during GH treatment. To identify GH-responsive genes that regulate substrate metabolism in muscle, we studied six hypopituitary men who underwent whole body metabolic measurement and skeletal muscle biopsies before and after 2 wk of GH treatment (0.5 mg/day). Transcript profiles of four subjects were analyzed using Affymetrix GeneChips. Serum insulin-like growth factor I (IGF-I) and procollagens I and III were measured by RIA. GH increased serum IGF-I and procollagens I and III, enhanced whole body lipid oxidation, reduced carbohydrate oxidation, and stimulated protein synthesis. It induced gene expression of IGF-I and collagens in muscle. GH reduced expression of several enzymes regulating lipid oxidation and energy production. It reduced calpain 3, increased ribosomal protein L38 expression, and displayed mixed effects on genes encoding myofibrillar proteins. It increased expression of circadian gene CLOCK, and reduced that of PERIOD. In summary, GH exerted concordant effects on muscle expression and blood levels of IGF-I and collagens. It induced changes in genes regulating protein metabolism in parallel with a whole body anabolic effect. The discordance between muscle gene expression profiles and metabolic responses suggests that muscle is unlikely to contribute to GH-induced stimulation of whole body energy and lipid metabolism. GH may regulate circadian function in skeletal muscle by modulating circadian gene expression with possible metabolic consequences.

Successful treatment of short stature with growth hormone replacement therapy in a patient with anorexia nervosa

2015 ◽  
Vol 29 (4) ◽  
Author(s):  
Yuji Koike ◽  
Masaya Akibayashi ◽  
Yukako Yokouchi
Keyword(s):  
Growth Hormone ◽  
Anorexia Nervosa ◽  
Replacement Therapy ◽  
Short Stature ◽  
Hormone Replacement ◽  
Bone Age ◽  
Delayed Puberty ◽  
Primary Amenorrhea ◽  
Gh Treatment ◽  
Igf I

Abstract A 19-year-old woman visited our outpatient clinic requesting treatment for short stature. She had been repeatedly hospitalized at a psychiatric unit and was subsequently diagnosed with anorexia nervosa (AN). She was 139.3 cm (–3.6 SD) tall and weighed 25.5 kg (23% lower than standard weight). She had primary amenorrhea and her bone age (BA) was 11.8 years. She had low insulin-like growth factor (IGF)-I (80 ng/mL) and a basal growth hormone (GH) level of 1.47 ng/mL. Treatment with recombinant GH was initiated. At 22 years of age, she was 152.2 cm (–1.1 SD) tall and weighed 39.7 kg. As she had shown a favorable response to GH treatment, therapy was discontinued. We suggest that it is worthwhile treating AN patients with GH replacement therapy for short stature, once low IGF-I levels without GH resistance, delayed puberty, delay in BA, and nutritional stabilization are taken into consideration.

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