Reconstruction of lateral skull base oncological defects: the role of free tissue transfer

The present study was performed to investigate the age-dependent changes in body composition and the possible role of growth hormone (GH), insulin-like growth factor (IGF)-I and IGF-binding protein-3 (IGFBP-3) in these changes in postmenopausal Japanese women. A total of 161 Japanese women aged 45-88 years (mean 62) were enrolled in the cross-sectional study. Body composition (bone mineral content (BMC), lean body mass (LBM) and fat) was measured by dual-energy X-ray absorptiometry, and the percentage of BMC, LBM and fat was calculated by dividing each absolute value of body composition by total body mass. Urinary GH concentration divided by creatinine in nocturnal urine samples collected just after waking was used as an index of endogenous GH secretion. Serum levels of IGF-I and IGFBP-3 were measured by RIA. Urinary GH levels as well as serum levels of IGF-I and IGFBP-3 declined with age. BMC, %BMC and LBM also declined with age, while fat mass and %fat did not obviously change with age. Urinary GH levels as well as serum levels of IGF-I and IGFBP-3 correlated positively with BMC, even if age was taken into account. On the other hand, urinary GH correlated negatively with fat and %fat. In contrast, serum levels of IGF-I and IGFBP-3 correlated positively with fat and %fat. LBM did not correlate with either urinary GH or serum IGFBP-3 levels but exhibited a weakly positive correlation with serum IGF-I level. The present study suggests that the GH-IGF-I-IGFBP-3 axis positively regulates bone mass, and that GH and IGF-I-IGFBP-3 inversely regulate fat mass, i.e. GH negatively and IGF-I-IGFBP-3 positively regulates it.     

High-dose growth hormone treatment of short children born small for gestational age

The effect of GH administration was evaluated over 2 yr in 50 short, prepubertal, non-GH deficient children born small for gestational age, who had been randomly allocated to a group receiving no treatment or daily sc GH treatment at a dose of 0.2 or 0.3 IU/kg. At the start of the study, mean age was 5.2 yr, bone age was 4.0 yr, height SDS was -3.5, height velocity SDS was -0.8, weight SDS was -2.7, and body mass index SDS was -1.9. Catch-up growth was observed in none of the untreated and all of the treated children. The response to GH treatment included a near doubling of growth velocity and of weight gain and a mean height increment of more than 2 SDS. GH treatment was associated with a distinct acceleration of bone maturation. The differences between the growth responses evoked by the two GH doses were minor. The prepubertal GH-induced catch-up growth was associated with elevated serum concentrations of insulin, insulin-like growth factor-I, insulin-like growth factor binding protein-3, and osteocalcin, whereas insulin-like growth factor-II levels remained unaltered. GH treatment was well tolerated. In conclusion, high-dose GH administration over 2 yr is emerging as a potential therapy to increase the short stature that results from insufficient catch-up growth in young children born small for gestational age. The long-term impact of this approach remains to be delineated.     

The effects of a low-fat dietary intervention and tamoxifen adjuvant therapy on the serum estrogen and sex hormone-binding globulin concentrations of postmenopausal breast cancer patients

The purpose of the study was to determine the effect of a low-fat dietary intervention, with or without concomitant tamoxifen adjuvant therapy, on serum estrogen and sex hormone-binding globulin (SHBG) levels in postmenopausal patients with resected breast cancer. Ninety-three patients were randomized to either reduce their fat intake to 15-20% of total calories, or to a dietary control group. Serum estradiol, estrone, estrone sulfate, and SHBG concentrations were assayed at baseline, and at 6, 12, and 18 months thereafter. In 19% of patients, the preintervention serum estradiol levels were below the sensitivity of the assay (5 pg/ml). Tamoxifen had no significant effect on serum estrogen levels, but produced an elevation in SHBG. Patients with reliably quantifiable preintervention estradiol concentrations (> or = 10 pg/ml) showed a significant reduction in serum estradiol after 6 months on the low-fat diet (average, 20%; p < 0.005); this was sustained over the 18 month study period. Serum SHBG levels were increased by tamoxifen therapy, but were reduced significantly (p = 0.01) after 12 months on the low-fat diet in patients not receiving tamoxifen. No changes in serum estrone or estrone sulfate resulted from the dietary intervention. While the low-fat diet produced significant weight loss, patients treated with tamoxifen without dietary intervention showed a gain in body weight. These weight changes produced disruptions in the normal positive correlation between body weight and serum estrone sulfate, and the negative correlation with SHBG concentration.     

Effects of short- and long-term dexamethasone treatment on growth and growth hormone (GH)-releasing hormone (GRH)-GH-insulin-like growth factor-I axis in conscious rats

Although the inhibitory effects of a chronic excess of glucocorticoids (GC) on body growth and GH secretion are well established, the mechanisms involved remain unclear. In this study, we examined the chronic effects of a high dose of dexamethasone (DEX) on spontaneous GH secretion and insulin-like growth factor (IGF)-I in conscious rats. The animals were given daily i.p. injections of DEX (200 microg/day) for either one or four weeks. Body growth assessed by tibia length and serum IGF-I levels was significantly inhibited 1 week after treatment. By contrast, spontaneous GH secretion was not altered 1 week after the treatment. Neither hypothalamic GRH and somtatostain mRNA levels nor GH responses to GRH from single somatotropes were affected 1 week after the treatment. Four weeks after DEX treatment, body growth of the rats was noticeably suppressed. Interestingly, spontaneous GH secretion, hypothalamic GRH mRNA levels and GH responses to GRH were all inhibited 4 weeks after treatment. Pituitary GRH receptor mRNA levels were not altered 1 week after treatment, but increased after 4 weeks. These results indicate that a high dose of DEX initially impairs IGF-I production and subsequently inhibits spontaneous GH secretion in rats. Inhibition of spontaneous GH secretion resulting from chronic GC excess is due, at least in part, to the impairment of hypothalamic GRH synthesis and pituitary GH responsiveness. An increase in the pituitary GRH receptor may be caused by decreased GRH secretion.     

Tamoxifen attenuates glucocorticoid actions on bone formation in vitro

Tamoxifen is a synthetic estrogen analog which may regulate osteogenesis in vivo by virtue of its antiglucocorticoid properties. We have examined tamoxifen regulation of glucocorticoid-induced osteogenesis in two different in vitro bone systems: the chicken periosteal osteogenesis model (CPO) and rat bone marrow stromal cells (RBMC). Hormone uptake studies were conducted with the osteosarcoma cell line, ROS 17/2.8. In the CPO model, alkaline phosphatase (AP) activity and collagen synthesis were stimulated by the glucocorticoid dexamethasone (Dex; 0.1 microM). These Dex-mediated effects were inhibited by increasing concentrations of tamoxifen (10-100 microM). Similarly, in the RBMC model, Dex-dependent (0.01 microM Dex) mineralized tissue formation and AP activity were blocked by tamoxifen (0.1 microM). Although tamoxifen inhibited Dex-mediated increases of AP activity in ROS 17/2.8 cells, it did not inhibit uptake of 3H-Dex or of 3H-estrogen. Northern analyses showed that tamoxifen did not affect messenger RNAs (mRNAs) for AP. Tamoxifen did seem to reduce mRNA for collagen type I, but not bone sialoprotein, osteopontin, and osteocalcin. Dex-induced increases for all proteins mRNAs in the RBMC model were not reduced by tamoxifen. Similarly, tamoxifen had no effects on cellular proliferation. We conclude that tamoxifen has no direct effect on gene expression of bone-related proteins of osteoblastic cells. Further, in the ROS 17/2.8 cell line, the antiglucocorticoid properties of tamoxifen do not appear to be mediated through either Dex or estrogen receptors.     

Control of cell growth. III. Direct mitogenic effect of thyroid hormones on an estrogen-dependent rat pituitary tumor cell line

A possible direct estrogen requirement for growth of GH3/C14 rat pituitary tumor cells was evaluated in culture medium supplemented with estrogen-depleted serum prepared by a 56 degree C charcoal extraction procedure, and with serum obtained from ovariectomized sheep and ovariectomized adrenalectomized sheep. Growth of the GH3/C14 cells in culture medium in which the final estrogen concentration was 2 pg/ml or less was equal to growth in medium with normal serum and equal to growth in the presence of estrogen-depleted serum to which estradiol was added back at concentrations of 10-1,000 pg/ml. Under no conditions could a direct estrogen requirement for growth be demonstrated. The function of thyroid hormones in cell growth was examined in culture medium supplemented with serum from thyroidectomized sheep. In such medium the growth of the GH3/C14 cells was stimulated 3.5-fold by addition of 1.0 X 10(-8) M L-thyroxine (T4) or 1.0 X 10(-9) m L-triiodothyronine (T3). Investigation of the possible synergistic effects of estrogens and T4 revealed that combinations of estrogen and T4 or T3 did not stimulate growth over that seen with T4 or T3 alone. These data indicated that estrogens are not direct growth requirements for these cells but instead operate in vivo through secondary or indirect mechanisms; in contrast, thyroid hormones are directly mitogenic in vitro.     

Hemichorea-hemiballism: an explanation for MR signal changes

Studies were performed to determine if the nonsteroidal anti-inflammatory drug ibuprofen alters bone and mineral metabolism in female rats. In experiment 1, four groups of growing rats underwent either sham operation or ovariectomy (OVX). One week later, controlled-release pellets with ibuprofen or placebo were implanted subcutaneously at the back of the neck. Following 3 weeks of treatment, rats were sacrificed and blood and bone samples were removed for serum assays and histomorphometric analysis. Body growth rate and the static cortical bone measurements made at the tibial diaphysis did not change in response to OVX. OVX, however, did increase radial bone growth, lowered serum 17beta-estradiol, reduced uterine weight, and decreased the cancellous bone area of the tibial metaphysis in the rats. Ibuprofen did not alter serum 17beta-estradiol or uterine weight but reduced radial bone growth as well as cancellous bone area of the tibial metaphysis in both sham-operated and OVX animals. In experiments 2 and 3, we tested the influence of ibuprofen on the effects of the tissue-selective estrogen agonist tamoxifen and of exogenous 17beta-estradiol in the OVX rat. Ibuprofen completely blocked the effects of tamoxifen and partially blocked the effects of 17beta-estradiol to prevent cancellous osteopenia. In contrast, ibuprofen did not influence the effects of tamoxifen and 17beta-estradiol to reduce radial bone growth. Besides the skeletal effects, ibuprofen suppressed estrogen-induced uterine growth. Our data suggest that ibuprofen blocks selective estrogen receptor-mediated activities in the rat.     

Effects of the antiestrogenic environmental pollutant 3,3',4,4', 5-pentachlorobiphenyl (PCB #126) in rat bone and uterus: diverging effects in ovariectomized and intact animals

The purpose of this study was to compare effects on rat bone and uterus of estrogen depletion and exposure to the coplanar PCB-congener 3,3',4,4',5-pentachlorobiphenyl (PCB #126) which exhibits anti-estrogenic properties. Half of the rats were ovariectomized (n = 20) and the other half were sham-operated. Ten of the ovariectomized rats and ten of the sham operated were exposed to PCB #126 (ip injections) for 3 months (total dose: 384 microgram/kg body wt). The remaining control rats were injected with corn oil (vehicle). The rats were killed and the tibiae and uteri were dissected. The left tibia was used for measurements of weight, length, and bone mineral density and the right for histomorphometrical analysis. The uteri were analyzed with respect to estrogen receptor content. PCB #126 exposure did not affect bone mineral density or trabecular bone volume of tibia in sham-operated rats. In ovariectomized rats PCB #126 exposure resulted in a decreased length and an increased bone mineral density of tibia. An obvious PCB #126 induced increase in osteoid surface was observed in sham-operated rats. The cortical thickness and the organic content of the tibia were also increased in these rats. In estrogen deprived tissue like the uteri of ovariectomized rats, PCB #126 showed weak estrogen agonistic activity. The observed effects of PCB #126 on bone and uterine tissues differed between ovariectomized and sham-operated rats.     

Tamoxifen and bone metabolism in postmenopausal low-risk breast cancer patients: a randomized study

PURPOSE: This trial was undertaken to evaluate the effect of adjuvant tamoxifen on bone metabolism in postmenopausal women undergoing surgery for low-risk breast cancer. PATIENTS AND METHODS: In an open trial, 25 women were randomized to receive tamoxifen 30 mg/d for 2 years, and 25 women constituted the control group. Twenty women treated with tamoxifen and 23 women in the control group provided data for the analysis. Inclusion criteria were operation for low-risk breast cancer and cessation of menstruations for more than 1 year. Exclusion criteria were presence of metastases, disorders of bone metabolism, contraindications against tamoxifen, use of drugs with influence on bone metabolism, ailments that made bone mineral measurements impossible, and age greater than 65 years. Repeated measurements of bone mineral density and content at the lumbar spine and forearms, serum alkaline phosphatase, phosphate, and ionized calcium were performed in all patients. RESULTS: Lumbar spine bone mineral density increased during the first year in women treated with tamoxifen and then stabilized, compared with decreased bone mineral density in the control group (P = .00074). Bone mineral content at the forearms remained almost stable in tamoxifen-treated women compared with a decrease in the control group (P = .024). Serum alkaline phosphatase, phosphate, and ionized calcium decreased in the tamoxifen group (P < .00001, P = .002, and P = .002, respectively). CONCLUSION: Tamoxifen has estrogen-like effects on bone metabolism that result in an increase and stabilization of bone mineral density in the axial skeleton and a stabilization of bone mineral content in the appendicular skeleton.     

The First Si-H Stretching Overtone of H3SiD: Emergence of Local Mode Effects

Vorozole, a selective aromatase inhibitor, was administered in ovo to test the specific embryonic role of estrogen in conferring the sex distinction in GH release and body phenotype in broilers. On Day 6 of incubation, eggs were injected with saline or with different concentrations of vorozole. Postnatal blood samples were analyzed for T3, T4, GH, estradiol (E2), and testosterone (T). At the age of 4 wk, control and vorozole-treated birds were cannulated, and serial blood samples were withdrawn every 10 min for 5 hr, wherein GH pulsatility characteristics were determined using deconvolution analysis. The proportional abdominal fat pad weight was reduced significantly in the treated groups, especially in female birds. The vorozole treatment increased plasma T3, E2, T, and GH concentrations, and decreased T4. The frequency of the GH pulses was lower and the interval between the bursts (min) was higher in the vorozole-treated group, as were the mass secreted per burst (ng/ml), the amplitude (ng/ml/min) and the production rate (ng/ml/5 hr). In conclusion, early in ovo treatment with a potent aromatase inhibitor is able to increase the mean serum T3 and GH concentration and masculinize the GH pulse pattern, resulting in an economically favorable decrease in abdominal fat pad content in male and female broilers at slaughter age.     

Peak bone mass in young healthy men is correlated with the magnitude of endogenous growth hormone secretion

GH plays a key role during adolescence in longitudinal bone growth and the attainment of peak bone mass. We explored the hypothesis that in early adulthood, bone mineral accretion and/or maintenance in men with normal GH and bone mineral status are related to the magnitude of endogenous GH secretion. Overnight plasma GH concentrations (sampled every 10 min from 2100-0500 h) were measured in 15 healthy, lean, Caucasian men (age, 24+/-1 yr; body mass index, 22.6+/-0.6 kg/m2; mean +/- SE). Total body, femur, and lumbar spine bone mineral mass/density were measured by dual energy x-ray absorptiometry. Total body and femoral bone mineral mass correlated with both total nocturnal GH and maximal GH concentrations even when bone mineral mass was adjusted by height (P = 0.005-0.02; r = 0.58-0.74). Neither spinal nor total body bone mineral density (BMD) correlated with GH. Maximum GH correlated with the BMD of all four femoral sites (P = 0.01-0.04; r = 0.55-0.66), whereas total nocturnal GH correlated with only one (trochanter; P = 0.01; r = 0.64) femoral site. Our data support the hypothesis that GH continues to play a role in the accretion and/or maintenance of bone mass in young men. This relationship is more evident in the bone mineral mass achieved than in the BMD.     

Changes in bone mineral density, body composition, and lipid metabolism during growth hormone (GH) treatment in children with GH deficiency

Adults with childhood onset GH deficiency (GHD) have reduced bone mass, increased fat mass, and disorders of lipid metabolism. The aim of the present study was to evaluate bone mineral density (BMD), bone metabolism, body composition, and lipid metabolism in GHD children before and during 2-3 yr of GH treatment (GHRx). Forty children with GHD, mean age 7.9 yr, participated in the study of bone metabolism and body composition; and an additional group of 17 GHD children, in the study of lipid metabolism. Lumbar spine BMD, total body BMD, and body composition were measured with dual-energy x-ray absorptiometry. Volumetric BMD (bone mineral apparent density, BMAD) was calculated to correct for bone size. BMD, BMAD, lean tissue mass, bone mineral content, fat mass, and percentage body fat were expressed as SD scores (SDS), in comparison with normative data of the same population. Lumbar spine BMD and BMAD and total body BMD were all decreased at baseline. All BMD variables increased significantly during GHRx, lumbar spine BMD SDS, already after 6 months of treatment. Lean tissue mass SDS increased continuously. Bone mineral content SDS started to increase after 6 months GHRx. Fat mass SDS decreased during the first 6 months of GHRx and remained stable thereafter. Biochemical parameters of bone formation and bone resorption did not differ from normal at baseline and increased during the first 6 months of GHRx. Serum 1,25 dihydroxyvitamin D increased continuously during GHRx, whereas PTH and serum calcium remained stable. Lipid profile was normal at baseline: Atherogenic index had decreased and apolipoprotein A1(Apo-A1) had increased after 3 yr of treatment. In conclusion, children with GHD have decreased bone mass. BMD, together with height and lean tissue mass, increased during GHRx. GHRx had a beneficial effect on lipid metabolism.     

Correlation between longitudinal bone growth, growth hormone, and insulin-like growth factor-I in prepubertal dogs

OBJECTIVE: To determine the association between longitudinal bone growth and concentrations of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in serum from prepubertal dogs. Animals-6 male 14-week-old German Shepherd Dogs. PROCEDURE: Blood was obtained every 30 minutes for 14 consecutive days. Concentrations of GH and IGF-I in serum were determined, using a canine-specific radioimmunoassay and conventional radioimmunoassay after acid-ethanol extraction, respectively. Simultaneous biplanar radiography was performed daily to measure bone growth. Spectral analysis was used to estimate specific features of GH secretion during an extended period. Multiple linear regression with different lag times between independent and dependent variables was used to determine the strongest predictors of bone growth. RESULTS: The power spectra of GH concentrations in serum had a primary peak at a frequency of 0.02 cycles/h or a periodicity of 50 h/cycle. A significant determinant of longitudinal bone growth was a lag time of 1 day in concentration of GH in serum. The relationship between IGF-I concentration in serum and bone growth was not significant. CONCLUSIONS: The primary frequency of GH secretion is outside the time frame of a single day and the concentration of GH in serum is a primary determinant of bone growth. CLINICAL RELEVANCE: A better understanding of the components of bone growth provide discernment to improved diagnosis and treatment of abnormal bone growth.     

Growth hormone improves body composition, fat utilization, physical strength and agility, and growth in Prader-Willi syndrome: A controlled study

BACKGROUND: Obesity and hypotonia in children with Prader-Willi syndrome (PWS) are accompanied by abnormal body composition and diminished energy expenditure resembling a growth hormone deficient state. Hypothalamic dysfunction in PWS often includes decreased growth hormone (GH) secretion, suggesting a possible therapeutic role for exogenous GH treatment. OBJECTIVES AND METHODS: After 6 months of observation to determine baseline growth rate, and with the use of a 12-month randomized controlled study design, the effects of GH treatment (1 mg/m2/d) on growth, body composition, strength and agility, pulmonary function, resting energy expenditure (REE), and fat utilization were assessed in 54 children with PWS (n = 35 treatment and n = 19 control). Percent body fat and bone mineral density were measured by dual x-ray absorptiometry. Indirect calorimetry was used to determine REE and to calculate respiratory quotients. RESULTS: Stimulated levels of GH in response to clonidine testing were low in all patients (peak, 2.0 ng/mL). After 12 months, GH-treated subjects showed significantly increased height velocity Z scores (mean, 1.0 1.7 to 4.6 2.9; P <.001), decreased percent body fat (mean, 46.3% 8.4% to 38.3% 10.7%; P <.001), and improved respiratory muscle function, physical strength, and agility (sit-ups, weight-lifts, running speed, and coordination). A significant decline in respiratory quotients occurred during GH therapy (0.81 to 0.77, P <.001), but total REE did not change. CONCLUSIONS: GH treatment of children with PWS accelerated growth, decreased percent body fat, and increased fat oxidation but did not significantly increase total REE. Improvements in respiratory muscle strength, physical strength, and agility also occurred, suggesting that GH treatment may have value in reducing some physical disabilities experienced by children with PWS.     

Differential presentation of cortical and trabecular peripheral bone mineral density in acromegaly

Growth hormone (GH) has been suggested as a therapeutic tool for the treatment of osteopenia. To assess the differential influence of growth hormone on cortical and trabecular bone, bone mineral densities (BMD) of the ultradistal radius were determined in 18 men and 19 women with clinically and biochemically confirmed acromegaly using peripheral computed tomography and a specialized scanner (Stratec XCT 900). The results were expressed in equivalents to hydroxyl-apatite (mg/ccm) and compared with the BMD of healthy controls (17 men, 34 women). Cortical bone mineral density was significantly higher in acromegalic women (295.2 +/- 18.4, X +/- SEM) and men (339.4 +/- 21.2) compared to healthy women (243.0 +/- 12.8) and men (272.2 +/- 15.9). In contrast, trabecular BMD did not differ between acromegalic patients (men: 161.0 +/- 16.1; women: 116.5 +/- 10.5) and controls (men: 158.0 +/- 12.2; women: 134.1 +/- 6.3). Acromegalic women showed a significant correlation between insulin-like growth factor (IGF-I) expression and cortical BMD, whereas in acromegalic men GH levels correlated significantly with cortical BMD. Greatly increased serum osteocalcin levels in both, acromegalic men (15.5 +/- 3.3 ng/ml) and women (12.9 +/- 1.8) compared to controls (men: 6.7 +/- 1.7; women: 7.7 +/- 1.0) indicates the activation of osteoblastic bone formation. This study revealed an increase in cortical BMD at the forearm; in acromegalic patients; though trabecular BMD did not differ from controls. The differential mineralization of cortical and trabecular bone in acromegaly may be indicative of the detrimental effect accompanying pituitary insufficiency can have on trabecular bone, despite substitution therapy, but could also be due to different reactivity of cortical and trabecular bone to GH and/or IGF I. The observable increase of bone mineral density in acromegaly suggests a potential use for GH in treating osteoporosis.     

Phase I/II trial of all-trans retinoic acid and tamoxifen in patients with advanced breast cancer

Because tamoxifen and all-trans-retinoic acid (ATRA) have additive antitumor effects in preclinical systems, we performed a Phase I/II clinical trial of this combination in patients with advanced breast cancer. Patients with potentially hormone-responsive advanced breast cancer were enrolled. All received 20 mg of tamoxifen by mouth daily. Consecutive cohorts of 3-6 patients were treated on odd-numbered weeks with ATRA at doses of 70, 110, 150, 190, or 230 mg/m2/day. Twenty-six patients were entered in this trial; 25 were evaluable. A dose of 230 mg/m2 ATRA produced unacceptable headache and dermatological toxicity, but doses < or = 190 mg/m2 were tolerable. Two of 7 patients with measurable disease responded. Seven of 18 patients with evaluable, nonmeasurable disease achieved disease stability for more than 6 months. Plasma AUCs on day 1 of successive weeks of treatment were stable over time. A nonsignificant decrease in serum insulin-like growth factor I levels was noted during treatment, but this trend was similar to that observed in three "control" patients treated with tamoxifen alone. When given with daily tamoxifen, the maximum tolerated dose of ATRA that could be given on alternate weeks was 190 mg/m2/day. This schedule of ATRA resulted in repeated periods of exposure to potentially therapeutic concentrations of ATRA. Declines in the serum insulin-like growth factor I concentrations observed in patients treated with tamoxifen and ATRA were similar to those observed in patients treated with tamoxifen alone. Objective responses were observed, some in patients who had previously progressed while receiving tamoxifen, suggesting that further studies would be of interest.     

Construction and in vivo efficacy of a replication-deficient recombinant adenovirus encoding murine growth hormone

We have constructed a recombinant, replication-deficient, first-generation adenovirus-encoding mouse GH (mGH), AdCMVmGH. This virus directed mGH production from an epithelial cell line in vitro in a dose-dependent manner. When injected into the quadriceps muscle or submandibular ducts of mGH-deficient Snell dwarf mice, AdCMVmGH resulted in the production of significantly elevated serum mGH levels. Furthermore, after i.m. injection, dwarf mice increased in weight by 8% over 4 days and close to 100% by 30 days. When AdCMVmGH was administered to 3- to 4-week-old rats by i.v. injection to assess general metabolic responses, serum mGH, insulin-like growth factor 1, triglycerides and cholesterol levels were significantly elevated. AdCMVmGH should be a valuable experimental tool for the controlled, directed expression of mGH in preclinical mouse model studies.     

Effect of growth hormone therapy on bone metabolism of growth hormone deficient children

The effects of human growth hormone (hGH) therapy on biochemical markers of bone metabolism were studied in 17 children (10 boys and 7 girls, aged 3.7-13.1 years old) with idiopathic GH deficiency, before and 1 and 6 months after GH therapy (0.5 0.7 IU/kg weekly SC). Serum levels of calcium, phosphate, alkaline phosphatase osteocalcin, parathyroid hormone, 1,25 dihydroxyvitamin D, insulin-like growth factor I (IGF-I) and renal phosphate per 100 ml glomerular filtrate (TPO4/GFR) were assessed. During therapy with hGH a significant decrease of serum calcium levels and increases of phosphate, osteocalcin, parathyroid hormone 1,25 dihydroxyvitamin D and IGF-I were observed. TPO4/GFR was also significantly increased. Growth response (increment in HV) was positively related with changes in alkaline phosphatase and IGF-I levels after 6 months of hGH therapy. There was also a significant positive correlation between increment in HV and increment in TPO4/GFR after 1 month of GH therapy, whereas no correlation between HV and changes in osteocalcin levels was found. CONCLUSION: GH treatment significantly influences mineral metabolism and the measurement of TPO4/ GFR after 1 month of GH therapy may serve as a useful predictor of growth response to hGH therapy in GH-deficient children.