Effects of oral administration of a synthetic fragment of human growth hormone on lipid metabolism

A small synthetic peptide sequence of human growth hormone (hGH), AOD-9401, has lipolytic and antilipogenic activity similar to that of the intact hormone. Here we report its effect on lipid metabolism in rodent models of obesity and in human adipose tissue to assess its potential as a pharmacological agent for the treatment of human obesity. C57BL/6J (ob/ob) mice were orally treated with either saline (n = 8) or AOD-9401 (n = 10) for 30 days. From day 16 onward, body weight gain in AOD-9401-treated animals was significantly lower than that of saline-treated controls. Food consumption did not differ between the two groups. Analyses of adipose tissue ex vivo revealed that AOD-9401 significantly reduced lipogenic activity and increased lipolytic activity in this tissue. Increased catabolism was also reflected in an acute increase in energy expenditure and glucose and fat oxidation in ob/ob mice treated with AOD-9401. In addition, AOD-9401 increased in vitro lipolytic activity and decreased lipogenic activity in isolated adipose tissue from obese rodents and humans. Together, these findings indicate that oral administration of AOD-9401 alters lipid metabolism in adipose tissue, resulting in a reduction of weight gain in obese animals. The marked lipolytic and antilipogenic actions of AOD-9401 in human adipose tissues suggest that this small synthetic hGH peptide has potential in the treatment of human obesity.     

The conformational and biological analysis of a cyclic anti-obesity peptide from the C-terminal domain of human growth hormone.

The three-dimensional solution structure of antiobesity drug (AOD), a 15-residue, disulfide-bonded, cyclic peptide, cyclo(6,13)-H2N-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe-OH, derived from the C-terminal domain of the human growth hormone (hGH) (residues 177-191) was determined using two-dimensional 1H NMR spectroscopy. AOD stimulates lipolysis and inhibits lipogenesis, in vitro, in rodent, porcine and human adipose tissues. These biological effects suggest that AOD is a potential therapeutic candidate for the treatment of obesity. Conformational studies of AOD were conducted in aqueous solution and in water/dimethylsulfoxide mixtures. In general, spectral quality was superior in the water/ dimethylsulfoxide mixtures. The cyclic region of AOD in water/dimethylsulfoxide adopts type I beta-turns at residues Ser8-Val9-Glu10-Gly11 and Ser12-Cys13-Gly14-Phe15, each preceded by loop-like structures. Comparison of the conformation of this peptide with residues 177-191 in the native hGH protein X-ray crystal structure indicates that the synthetic peptide retains some structural similarity to the intact protein. This study provides evidence that the C-terminal region of hGH is a specific functional domain of the multifunctional hGH protein.     

Stress-induced secretion of human growth hormone in transgenic mice

The effect of stress on human growth hormone (hGH) secretion was studied in transgenic mice. Experiments were conducted on fourth, fifth, and sixth generation male mice carrying a fusion gene, consisting of the promoter sequence of the mouse metallothionein I gene ligated to the hGH structural gene (mMT-I/hGH). In animals adapted to a controlled photoperiod, basal (unstimulated) levels of plasma hGH exhibited a diurnal cycling, with peak values occurring during the later half of the light period (15.5 +/- 1.0 vs 10.7 +/- 0.9 ng/ml, mean +/- SE, light versus dark, respectively). Food deprivation (5 days) led to elevated levels of plasma hGH (11.0 +/- 0.7 vs 32.0 +/- 4.2 ng/ml, preversus post-fast, respectively) accompanied by weight loss (49.5 +/- 0.8 vs 34.3 +/- 0.7 g), and hypoglycemia (7.8 +/- 0.2 vs 5.0 +/- 0.3 mM); glucose administration (5% drinking solution ad libitum) blocked the changes in levels of plasma hGH (12.2 +/- 1.1 vs 13.8 +/- 0.8 ng/ml) and plasma glucose (7.4 +/- 0.3 vs 7.9 +/- 0.5 mM), although the animals still sustained significant weight loss (44.9 +/- 1.6 vs 35.2 +/- 1.1 g). Vigorous exercise (swimming, 4 hr) produced a small but significant increase in plasma hGH, 12.1 +/- 1.1 ng/ml (1 hr pre-swim) vs 16.7 +/- 0.6 ng/ml (immediately post-swim). These findings indicate that the mMT-I/hGH transgene is responsive to the physiologic status of the host animal. Taken together with information regarding the heterologous components of the fusion gene, these data are consistent with the view that the hGH (structural) sequence may play a role in the response to stress.     

Differential effects of hGH and IGF-I on body proportions

The differential growth effects of hGH and IGF-I on the upper/lower (U/L) body segment in relation to height (Ht) were analyzed in 15 patients with isolated Growth hormone deficiency (IGHD,:7M, 8F) mean age 5.0 +/- 3.2 (SD) years treated with hGH; 21 patients with multiple pituitary hormone deficiency including growth hormone (MPHD: 14M, 7F) aged 10.0 +/- 3.8, treated with hGH; 9 patients with Laron Syndrome (LS) (4M,5F) aged 6.9 +/- 5.6 years treated with IGF-I; 9 boys with intrauterine growth retardation (IUGR) aged 6.3 +/- 1.25 years treated by hGH; and 22 boys with idiopathic short stature (ISS) aged 8.0 +/- 1.55 years treated by hGH. The dose of hGH was 33 microg/kg/day, that of IGF-I 180-200 microg/kg/day. RESULTS: the U/L body segment ratio in IGHD patients decreased from 2.3 +/- 0.7 to 1.1 +/- 0.7 (p <0.001), and the Ht SDS increased from -4.9 +/- 1.3 to 2.3 +/- 1 (p < 0.001) following treatment. In MPHD patients the U/L body segment decreased from 1.1 +/- 1.1 to -0.6 +/- 1.0 (p < 0.001), and the Ht SDS increased from -3.3 +/- 1.4 to -2.5 +/- 1.0 (p < 0.009). In the LS group the U/L body segment ratio did not change with IGF-I treatment but Ht improved from -6.1 +/- 1.3 to -4.6 +/- 1.2 (p < 0.001), The differential growth response of the children with IUGR and with ISS resembled that of the children with LS. CONCLUSIONS: hGH and IGF-I act differentially on the spine and limbs.     

Non-conventional use of growth hormone: European experience

Results from several centres in Europe using biosynthetic human growth hormone (hGH) for the promotion of growth in a variety of conditions other than classical hGH deficiency were evaluated. Significant increments in growth rates were achieved by daily administration of hGH in doses appropriate for body size without disproportionate skeletal advances in short normals, Turner syndrome, low birth weight, skeletal dysplasia, central precocious puberty (reared with gonadotrophin-releasing hormone analogue) and renal failure.     

Low-dose growth hormone treatment with diet restriction accelerates body fat loss, exerts anabolic effect and improves growth hormone secretory dysfunction in obese adults.

Growth hormone (GH) can induce an accelerated lipolysis. Impaired secretion of GH in obesity results in the consequent loss of the lipolytic effect of GH. Dietary restriction as a basic treatment for obesity is complicated by poor compliance, protein catabolism, and slow rates or weight loss. GH has an anabolic effect by increasing insulin-like growth factor (IGF)-I. We investigated the effects of GH treatment and dietary restriction on lipolytic and anabolic actions, as well as the consequent changes in insulin and GH secretion in obesity. 24 obese subjects (22 women and 2 men; 22-46 years old) were fed a diet of 25 kcal/kg ideal body weight (IBW) with 1.2 g protein/kg IBW daily and were treated with recombinant human GH (n = 12, 0.18 U/kg IBW/week) or placebo (n = 12, vehicle injection) in a 12-week randomized, double-blind and placebo-controlled trial. GH treatment caused a 1.6-fold increase in the fraction of body weight lost as fat and a greater loss of visceral fat area than placebo treatment (35.3 vs. 28.5%, p < 0.05). In the placebo group, there was a loss in lean body mass (-2.62 +/- 1.51 kg) and a negative nitrogen balance (-4.52 +/- 3.51 g/day). By contrast, the GH group increased in lean body mass (1.13 +/- 1.04 kg) and had a positive nitrogen balance (1.81 +/- 2.06 g/day). GH injections caused a 1.6-fold increase in IGF-I, despite caloric restriction. GH response to L-dopa stimulation was blunted in all subjects and it was increased after treatment in both groups. GH treatment did not induce a further increase in insulin levels during an oral glucose tolerance test (OGTT) but significantly decreased free fatty acid (FFA) levels during OGTT. The decrease in FFA area under the curve during OGTT was positively correlated with visceral fat loss. This study demonstrates that in obese subjects given a hypocaloric diet, GH accelerates body fat loss, exerts anabolic effects and improves GH secretion. These findings suggest a possible therapeutic role of low-dose GH with caloric restriction for obesity.     

Biosynthetic human growth hormone: effects on growth of Snell dwarf mice

Bacterially synthesized human growth hormone (bhGH) administered to Snell dwarf mice during 4 weeks, induced an increase in body length and weight to a comparable degree as obtained with pituitary-derived human growth hormone (hGH). At a dose of 150 mU/day both bhGH and hGH induced a significant stimulation over saline-treated controls, of the weight of the submandibular salivary glands, the m. quadriceps femoris and gastrocnemius, the heart, liver, kidneys, thymus and spleen. The weight of the brain and the thickness of the skinfold were not influenced by either of the preparations used. When organ weights were expressed as a function of body weight, the contribution of the kidneys to body weight was significantly higher with hGH than with bhGH. The other organs studied did not show differences. As a biochemical parameter of cartilage growth, the sulfate incorporation into costal and epiphyseal cartilage in vitro was measured, and it was found to be stimulated by both hormones after short-term treatment. Thus bacterially synthesized hGH behaves identically to pituitary-derived hGH with respect to body length, sulfate incorporation into costal and epiphyseal cartilage, body weight and organ growth of Snell dwarf mice, with one exception: increase of weight of the kidneys, as a function of body weight, was more pronounced after treatment with hGH than with bhGH.     

The clinical usefulness of liquid human growth hormone (hGH) (Norditropin SimpleXx in the treatment of GH deficiency

Human growth hormone (hGH) is an essential therapeutic drug for the treatment of GH deficiency. The development of recombinant GH using a pen injection system has enabled easy and safe treatment of GH-deficient patients; however, the process of dissolving hGH in the powder form is complicated and dangerous. In this study, we investigated the usefulness of a newly developed liquid form of hGH (Norditropin((R)) SimpleXx(TM)) in the treatment of 51 patients with GH deficiency. Fifteen previously untreated patients with GH deficiency were treated with liquid hGH (group A), and 36 patients who had previously used hGH in the powder form were changed to the liquid form (group B). Both groups were treated with liquid hGH 0.5 IU/kg per week for 6 months. The growth rate of patients in group A increased from 4.0 +/- 2.4 cm/year to 9.2 +/- 2.9 cm/year. The patients in group B continued to grow at the same rate as before using the liquid hGH therapy. Questionnaires to the patients in group B demonstrated that 85% preferred the convenience of using the new liquid form of hGH. Our results indicate that liquid hGH has similar efficacy to that of powder hGH, but its improved convenience may have a beneficial effect on patient compliance.     

Chronic infusion of norepinephrine into the VMH of normal rats induces the obese glucose-intolerant state

Increases in ventromedial hypothalamic (VMH) norepinephrine (NE) levels and/or activities have been observed in a variety of animal models of the obese insulin-resistant condition. This study examined the metabolic effects of chronic NE infusion (25 nmol/h) into the unilateral VMH of normal rats. Within 4 days, VMH NE infusion significantly increased plasma insulin (140%), glucagon (45%), leptin (300%), triglyceride (100%), abdominal fat pad weight (50%), and white adipocyte lipogenic (100%) and lipolytic (100%) activities relative to vehicle-infused rats. Furthermore, isolated islet insulin secretory response to glucose (15 mM) within 4 days of such treatment was increased over twofold (P < 0.05). Among treated animals, fat stores continued to increase over time and plateaued at approximately 2 wk (3-fold increase), remaining elevated to the end of the study (5 wk). By week 4 of treatment, NE infusion induced glucose intolerance as evidenced by a 32% increase in plasma glucose total area under the glucose tolerance test curve (P < 0.01). Whole body fat oxidation rate measured after 5 wk of infusion was significantly increased among treated animals as evidenced by a reduced respiratory quotient (0.87 +/- 0.01) relative to controls (0. 90 +/- 0.01). VMH NE infusion induced hyperphagia (30%) only during the first week and did not affect body weight over the 5-wk period. Increases in VMH NE activity that are common among obese insulin-resistant animal models can cause the development of this obese glucose-intolerant (metabolic) syndrome.     

Effects of recombinant human growth hormone in juvenile Nile crocodiles (Crocodylus niloticus)

1. Recombinant human growth hormone (hGH) showed somatotropic activity in juvenile Nile crocodiles (Crocodylus niloticus). 2. Body weight of crocodiles receiving 3.25 micrograms hGH/g body weight twice a week was increased by 49% after five weeks of treatment, compared to 31% increase in controls. 3. Total length was increased by 15 and 5%, respectively, in the two groups. 4. Food conversion efficiency increased from 28% in the controls to 36% in the hormone injected animals. 5. Cessation of hormone treatment was followed by reduced appetite and decreasing body growth.     

A comparison of subcutaneous and intramuscular administration of human growth hormone (hGH) and increased growth rate by daily injection of hGH in GH deficient children

Plasma human growth hormone (hGH) profiles and biological activities of recombinant hGH were compared after im and sc injection in 8 normal volunteers. The time to reach maximal plasma GH and plasma hGH concentrations and the areas under the curve of hGH profiles did not differ significantly after im and sc injections. The biological effect of hGH in increasing nonesterified fatty acid and insulin-like growth factor-I (IGF-I) was the same after both im and sc injections. During 6 months of daily sc administration of recombinant hGH in 20 naive patients, their height increased between 5 and 16.5 cm with a mean of 11.0 +/- 3.0 cm/year. In 27 patients who switched from hGH injections of 2-4 times/week to daily injections, the height increased between 5.3 and 16.5 cm with a mean of 8.3 +/- 2.2 cm/year. These values were greater than those observed in a previous study in which the same amount of hGH was injected in 2-4 doses per week. Plasma IGF-I increased more with daily sc administration than with 2-4 doses per week. The rate of appearance of an antibody to hGH was low (0.5%) and there were no notable changes in blood cell count, urinalysis and/or routine chemistries during the 6 months of daily recombinant hGH treatment. These results show that sc daily administration of hGH is safe, has a greater growth promoting effect, and can be recommended for the treatment of patients with GH deficiency.     

Histochemical characteristics of soleus muscle in hGH transgenic mice

Histochemical characteristics of soleus muscle were compared in human growth hormone (hGH) transgenic mice vs their nontransgenic littermates. Plasma of transgenic mice contained hGH (7.1 +/- 0.7 and 6.7 +/- 0.4 ng/ml, mean +/- SE, at 5 and 11 months of age, respectively); hGH was not detectable in plasma of nontransgenic littermates. Body and soleus weights were greater (approximately 55 and 25%, respectively) and both type I and type IIA fibers were larger in transgenic animals. Most significantly, fiber type composition of the soleus muscle was different in hGH-transgenic animals, i.e., the percentage of type I fibers was significantly greater than in nontransgenic mice (77.2 +/- 5.1% vs 58.4 +/- 2.5%). It is generally believed that skeletal muscle fiber composition is determined predominantly by neural influences (1, 2). These data suggest hormonal factors, growth hormone, also affect the phenotype of skeletal muscle myosin.     

Effect of aging and cellularity on lipolysis in isolated mouse fat cells

The effects of age and cellularity on lipolysis have been investigated in isolated epididymal fat cells from both Swiss albino mice and Sprague-Dawley rats. No significant lipolytic response to glucagon could be demonstrated with adipocytes from either young or old mice, while glycerol output was increased by this hormone with fat cells from young rats. Larger adipocytes from older mice showed significantly greater isoproterenol-stimulated lipolysis than those from younger animals if the glycerol output was expressed on a per cell basis. However, the lipolytic response per cell appeared to be equivalent in young and old rat adipocytes with either isoproterenol or ACTH-(1-24). In a complete aging study, relationships between body weight, epididymal fat pad weight and cellularity were examined covering the life span of the mouse. ACTH-(1-24)- and dibutyryl cyclic AMP-stimulated lipolysis increased with age and cell size but fell at senescence when adipocyte size diminished. Although an effect of aging per se cannot be ruled out with the experimental techniques used in the present study, a dominant influence of adipocyte size on the lipolytic process was demonstrated.     

Growth hormone pulsatility profile characteristics following acute heavy resistance exercise.

This investigation examined the hypothesis that acute heavy resistance exercise (AHRE) would increase overnight concentrations of circulating human growth hormone (hGH). Ten men (22 +/- 1 yr, 177 +/- 2 cm, 79 +/- 3 kg, 11 +/- 1% body fat) underwent two overnight blood draws sampled every 10 min from 1700 to 0600: a control and an AHRE condition. The AHRE was conducted from 1500 to 1700 and was a high-volume, multiset exercise bout. Three different immunoassays measured hGH concentrations: the Nichols immunoradiometric assay (Nichols IRMA), National Institute of Diabetes and Digestive and Kidney Diseases radioimmunoassay (NIDDK RIA), and the Diagnostic Systems Laboratory immunofunctional assay (DSL IFA). The Pulsar peak detection system was used to evaluate the pulsatility profile characteristics of hGH. Maximum hGH was lower in the exercise (10.7 microg/l) vs. the control (15.4 microg/l) condition. Mean pulse amplitude was lower in the exercise vs. control condition when measured by the Nichols IRMA and the DSL IFA. A differential pattern of release was also observed after exercise in which hGH was lower in the first half of sleep but higher in the second half. We conclude that AHRE does influence the temporal pattern of overnight hGH pulsatility. Additionally, because of the unique molecular basis of the DSL IFA, this influence does have biological relevance because functionally intact molecules are affected.     

Whole body and abdominal lipolytic sensitivity to epinephrine is suppressed in upper body obese women

We measured whole body and regional lipolytic and adipose tissue blood flow (ATBF) sensitivity to epinephrine in 8 lean [body mass index (BMI): 21 +/- 1 kg/m(2)] and 10 upper body obese (UBO) women (BMI: 38 +/- 1 kg/m(2); waist circumference >100 cm). All subjects underwent a four-stage epinephrine infusion (0.00125, 0.005, 0.0125, and 0.025 microgram. kg fat-free mass(-1). min(-1)) plus pancreatic hormonal clamp. Whole body free fatty acid (FFA) and glycerol rates of appearance (R(a)) in plasma were determined by stable isotope tracer methodology. Abdominal and femoral subcutaneous adipose tissue lipolytic activity was determined by microdialysis and (133)Xe clearance methods. Basal whole body FFA R(a) and glycerol R(a) were both greater (P < 0.05) in obese (449 +/- 31 and 220 +/- 12 micromol/min, respectively) compared with lean subjects (323 +/- 44 and 167 +/- 21 micromol/min, respectively). Epinephrine infusion significantly increased FFA R(a) and glycerol R(a) in lean (71 +/- 21 and 122 +/- 52%, respectively; P < 0.05) but not obese subjects (7 +/- 6 and 39 +/- 10%, respectively; P = not significant). In addition, lipolytic and ATBF sensitivity to epinephrine was blunted in abdominal but not femoral subcutaneous adipose tissue of obese compared with lean subjects. We conclude that whole body lipolytic sensitivity to epinephrine is blunted in women with UBO because of decreased sensitivity in upper body but not lower body subcutaneous adipose tissue.     

Regulation of growth hormone and epidermal growth factor receptors by progestins in breast cancer cells

A 24 hr incubation of T-47D human breast cancer cells with R5020, a synthetic progestin, resulted in a 200-250% increase in the specific binding of human growth hormone (hGH) and epidermal growth factor (EGF) by these cells. This effect was specific for progestins in that similar responses were observed with progesterone, medroxyprogesterone acetate and ORG 2058 but no significant increases in hGH or EGF binding were observed in cells incubated with testosterone, estradiol or hydrocortisone. Increased binding was due to an increase in the concentration of receptors (hGH, control = 6,490 +/- 500, progestin treated = 13,180 +/- 3,270 sites/cell; EGF, control = 33,380 +/- 7,410, progestin treated = 67,460 +/- 20,330 sites/cell) while the affinity constants for the hormone-receptor interactions were unchanged by progestin treatment. The specific binding of insulin, calcitonin, transferrin and concanavalin A was unaffected by these treatments. It is concluded that expression of hGH and EGF receptors in this breast cancer cell line is regulated by progestins.     

Factors attenuating growth promoting effect of growth hormone therapy for Turner's syndrome

Nine patients with Turner's syndrome aged 7 to 13 years were treated with recombinant human growth hormone (hGH) at a dose of 0.5 or 1.0 U/kg/w for 1 year. In five of them the growth rate was accelerated from 3.3 +/- 0.6 (SD) to 6.5 +/- 0.5 cm/y (group A), whereas 4 had a reduced rate of growth promotion (3.4 +/- 0.3 to 4.6 +/- 0.4 cm/y) (group B). Analysis of factors affecting growth response to hGH revealed 3 major parameters: (1) age of initiating hGH therapy (A, 9.5 +/- 2.1 vs B, 13.3 +/- 0.4 yrs, P less than 0.01), (2) basal LH (A, 3.2 +/- 2.4 vs, B, 44.9 +/- 17.8 mIU/ml, P less than 0.001) and FSH levels (A, 14.7 +/- 15.4 vs B, 131 +/- 49 mIU/ml; P less than 0.01) and (3) somatomedin-C (SM-C) producing capacity: coefficient of correlation to growth rate, r = 0.80, P less than 0.01). No remarkable changes were observed in the results of glucose tolerance, thyroid state, calcium metabolism and liver function tests. These results indicate that patient's age is the most crucial factor in effective treatment with hGH, and in adolescent girls, gonadal failure with a limited increase in SM-C production attenuates the growth promoting potency of hGH.     

Effects of hypophysectomy and the insulin-like and anti-insulin pituitary peptides on carbohydrate metabolism in yellow Avy/A (BALB/c x VY)F1 hybrid mice

The amino-terminal portion of human growth hormone, residues 1-43 (hGH1-43), has insulin-potentiating action, while a hyperglycemic pituitary peptide (HP), which co-purifies with human growth hormone (hGH), is antagonistic to the action of insulin. The effects of hGH, hGH1-43, and HP on glucose metabolism were assessed in young (4-5 weeks) and adult (6-8 months) hypophysectomized yellow Avy/A mice which lacked any interfering endogenous pituitary hormones, and compared with age-matched intact obese yellow Avy/A and lean agouti A/a mice. Treatment with hGH1-43 or HP did not promote body growth in hypophysectomized yellow mice; but after 2 weeks of treatment with hGH, there was a significant increase in body weight (P less than 0.05). Treatment with HP raised blood glucose and lowered insulin concentrations in obese yellow mice, but not in agouti or hypophysectomized yellow mice. The severely impaired glucose tolerance of the hypophysectomized yellow mice was improved by acute (60 min) and chronic (3 days) treatment with hGH1-43 as well as by 2 weeks of treatment with hGH; in contrast, HP had no effect. Glucose oxidation in adipose tissue from obese yellow mice was low and showed essentially no response to stimulation by insulin at doses lower than 1000 microunits/ml. Basal glucose oxidation rates in adipose tissue taken from agouti and hypophysectomized yellow mice were significantly higher (P less than 0.001) than those in tissue from obese yellow mice, and the rates responded significantly (P less than 0.05) to 100 microunits/ml insulin. The insulin binding affinities in liver membranes from agouti mice were higher than those from either obese or hypophysectomized yellow mice. The insulin receptor densities were similar in both agouti and obese yellow mice, but higher in hypophysectomized yellow mice (P less than 0.05). Treatment with hGH1-43 slightly increased, although not significantly, the insulin receptor density in yellow obese mice while hGH showed essentially no change. Therefore, hypophysectomy appeared to increase tissue response and decrease insulin resistance by increasing receptor numbers and lowering the circulating insulin levels. Furthermore, the insulin-like action of hGH was elicited directly in vivo by hGH1-43 in hypophysectomized yellow mice.     

Effect of a recombinant human growth hormone preparation on the urinary 15nitrogen balance in growth-hormone-deficient children

In 10 patients with idiopathic growth hormone (GH) deficiency (9 boys and 1 girl, aged 7.5-14.5 years, mean 12.1 +/- 2.2 years), urinary 15N-balance studies were performed before and on recombinant hGH (2 x 3 IU/m2 of body surface area subcutaneously on consecutive days). Before and on the 2nd day of recombinant hGH, 99% 15N-labeled ammonium chloride (0.05 g/kg, divided in 3 doses per day, corresponding to 389 +/- 30 mg/m2 of 15N) was administered and 24 h urine was collected. In urine, total nitrogen and the percentage of 15N were measured. From the ingested and excreted quantity, a urinary 15N balance was calculated. Mean 15N percentage from total N was 3.3 +/- 0.5. In 9 patients, basal 15N balance was +79 +/- 15 mg/m2 or +2.9 +/- 0.4 mg/kg. On recombinant hGH, it was +166 +/- 16 mg/m2 or +6.1 +/- 0.6 mg/kg (p less than 0.001). The recombinant hGH-induced positive 15N balance change was +87 +/- 17 mg/m2 or +3.2 +/- 0.6 mg/kg. 1 patient with a higher basal 15N balance (+196 mg/m2, +7.1 mg/kg) had no positive 15N balance change due to latent hypothalamic hypothyroidism. In previous similar studies with pituitary hGH the change of 15N balance was +80 +/- 27 mg/m2 or +2.8 +/- 1.1 mg/kg. It is concluded that the acute nitrogen-retaining effect of recombinant hGH is at least equal to that of pituitary hGH.