Somatomedin levels in the diagnosis and therapy of growth hormone deficiency

Serum somatomedin-C (SM-C) and somatomedin (SM) concentrations were measured by, respectively, radioimmuno (SM-C RIA) and radioreceptor assays (SM RRA) in 3 groups of children with short stature. The patient population was different from previously reported series in that it was urban Brazilian, low income, and significantly older. Group A consisted of 6 male and 3 female children, aged 7.7-16.0 years, whose average peak plasma immunoreactive growth hormone (GH) was above 10 ng/ml. Group B contained 8 male and 5 female untreated GH-deficient patients, ranging in age from 9.5 to 21.0 years. In Group C there were 4 male and 1 female GH-deficient subjects treated with I.M. injections of GH (0.1 U/kg) from 1 month to 7 years. The mean +/- SE basal RIA SM-C (ng/ml) concentrations were significantly lower in groups B (34.2 +/- 8.8) and C (43.8 +/- 13.7) than A (214.3 +/- 42.7): A X B, P less than 0.001 and A X C, P less than 0.02. Likewise the mean +/- SE basal RRA SM (ng/ml) concentrations were significantly lower in groups B (78.9 +/- 17.6) and C (90.8 +/- 19.3) than group A (316.3 +/- 43.0): A X B, P less than 0.001 and A X C, P less than 0.002. A significant linear correlation was observed between RIA and RRA in group B (r = 0.84; P less than 0.001) and C (r = 0.96; P less than 0.01), but not for A (r = 0.61; P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Insulinhypoglycemia but not arginine infusion stimulates circulating plasma growth hormone-releasing hormone (GHRH) concentrations in children

The effect of insulinhypoglycemia and arginine infusion on circulating concentrations of plasma growth hormone-releasing hormone (GHRH) and growth hormone (GH) has been studied in 24 children (4.4 to 14.3 years). Plasma GH and GHRH concentrations were determined by RIA. Basal plasma GHRH levels were detectable in the plasma of all patients ranging from 6.8 to 27.1 pg/ml. Injection of 0.1 U/kg body wt. insulin i.v. resulted in an increase of plasma GHRH levels (11.1 +/- 1.4 pg/ml vs. 18.8 +/- 2.6 pg/ml; P less than 0.01) preceding that of plasma GH (1.5 +/- 0.4 ng/ml vs. 13.6 +/- 1.3 ng/ml; P less than 0.01). Infusion of 0.5 gm/kg body wt. arginine hydrochloride did increase GH concentrations (2.0 +/- 0.6 ng/ml vs. 13.9 +/- 2.3 ng/ml; P less than 0.01) but did not change circulating plasma GHRH levels. Since the source of peripheral GHRH concentrations is not known the importance of these findings remains to be determined.     

Idiopathic central precocious puberty in girls as a model of the effect of plasma estradiol level on growth, skeletal maturation and plasma insulin-like growth factor I

Girls suffering from idiopathic central precocious puberty (CPP) may have different levels of estrogenic activity. This study was performed to evaluate the relationship between the estrogenic activity and the hypothalamopituitary activation and the effect of various plasma estradiol (E2) levels on growth, skeletal maturation and plasma insulin-like growth factor I (IGF-I). Fifty-eight girls with CPP were divided into 2 groups: group I with E2 less than 25 pg/ml (13 +/- 1 pg/ml, mean +/- SEM, n = 26) and group II with E2 greater than or equal to 25 pg/ml (52 +/- 3 pg/ml, n = 32). The mean ages at onset and at evaluation were lower in group I (5.9 +/- 0.4 and 6.8 +/- 0.4 years) than in group II (6.8 +/- 0.3 and 8.1 +/- 0.2 years, p less than 0.01), but the durations since onset (greater than 0.5 and less than 2 years) in the two groups were similar. The mean peak luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratios were lower in group I (0.8 +/- 0.2) than in group II (1.7 +/- 0.2, p less than 0.001) and correlated with E2 (r = 0.41, p less than 0.01). The mean height gains during the year preceding the initial evaluation were similar in the two groups (8.7 +/- 0.5 vs. 9.2 +/- 0.4 cm). They were independent of the plasma E2 level. Conversely, the mean plasma IGF-I values were lower in group I (2.4 +/- 0.3 U/ml) than in group II (4.2 +/- 0.6 U/ml, p less than 0.01) and correlated with E2 (r = 0.52, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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.     

Treatment of 94 patients with Turner's syndrome with recombinant human growth hormone (SM-9500) for two years--the results of a multicentric study in Japan. Committee for the Treatment of Turner's Syndrome

A total of 94 patients with Turner's syndrome were treated with methionine-free recombinant hGH for one to two years. Forty-seven patients were treated with r-hGH at a weekly dosage of 0.5 IU/kg and another 47 were treated with 1.0 IU/kg/w by daily sc injection. Both treatment groups showed statistically significant growth increase during the treatment from 3.7 +/- 1.0 to 5.2 +/- 1.3 and from 3.5 +/- 0.9 to 6.3 +/- 1.4 (Mean +/- SD) cm/year, respectively, during the first year of treatment. During the 2nd year of treatment, the growth rate declined to 4.1 +/- 1.1 cm/year under 0.5 IU/kg/w treatment and to 4.6 +/- 1.1 cm/year under 1.0 IU/kg/w treatment. Nevertheless, the growth rates in the treatment groups remained significantly greater than in the untreated controls. Plasma somatomedin C increased and no remarkable increase in bone age was observed during the treatment in either treatment group. Antibody to hGH was observed in 14.8% of the patients at the end of the first year of treatment, however the incidence was decreased to 4.7% by the end of the second year of treatment. Otherwise, there were no significant changes detected in physical or laboratory tests. No glucose intolerance necessitating treatment was observed. These results indicate that hGH treatment is useful in accelerating growth in patients with Turner's syndrome.     

Multicenter clinical trial to evaluate the therapeutic use of recombinant growth hormone from mammalian cells in the treatment of growth hormone neurosecretory dysfunction

The efficacy and safety of a 12-month treatment with recombinant human growth hormone from mammalian cells (r-hGH, Saizen) in growth hormone neurosecretory dysfunction (GHND) are evaluated in this study. r-hGH was administered subcutaneously, at a dosage of 0.5 IU/kg/week divided into 6 equal daily doses. A total of 16 (12 M and 4 F) poorly growing patients, height -2.3 SD or more below the mean for chronological age and sex, were included in the study. r-hGH therapy significantly increased the growth velocity; from 3.57 +/- 0.85 cm/year, before therapy, to 7.09 +/- 2.29 cm/year after 12 months (p less than 0.001). Patients' height SD score rose from -3.40 +/- 0.84 SDS to -2.98 +/- 0.69 SDS (p less than 0.01). Somatomedin C increased significantly from a baseline value of 0.59 +/- 0.32 U/ml to 1.26 +/- 0.66 U/ml after therapy (p less than 0.01). Finally, r-hGH therapy improved the pretreatment adult height prediction; from an initial prognosis of -2.66 +/- 0.79 SDS to -2.17 +/- 0.81 SDS after treatment (p less than 0.01). No side effects or adverse reactions were observed during treatment. Anti-r-hGH antibody formation was not found in any of the patients included in the study.     

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.     

Spontaneous growth hormone secretion and plasma somatomedin-C in children of short stature

We studied 17 short prepubertal children, aged 7.5 to 17.0 years (mean +/- SD: 11.7 +/- 2.4) more than 2.0 SD below the mean height for their age and of delayed bone age (M +/- SD: 8.1 +/- 2.3), to clarify their physiological GH secretory status. The mean concentration of GH (MCGH) was calculated and was compared with the subjects' GH responses to insulin and arginine tolerance tests (IATT) and plasma somatomedin-C (SM-C). The mean 24-h MCGH value was 3.2 +/- 1.3 ng/ml (range 1.6-5.5). The mean peak GH response to the IATT was 13.0 +/- 7.5 ng/ml (range 2.4-33.9). In addition to the two patients with abnormally low GH responses to the IATT, seven with normal responses showed low 24-h MCGH values, a small number of GH pulses and low mean GH amplitude. The mean plasma SM-C in all patients was 0.60 +/- 0.20 U/ml. This was significantly lower than that of age-matched children of normal height (p less than 0.001). The 24-h MCGH was significantly correlated with plasma SM-C levels (r = 0.51, p less than 0.05) and with that of the first three hours of sleep at night (r = 0.84, p less than 0.01). These results indicate that: 1) some short children with normal GH response to pharmacological tests secrete a low amount of GH physiologically and 2) blood sampling during the first three hours of sleep as well as 24-hour sampling is suitable in evaluating the physiological secretion of GH.     

Chronic administration of sodium cyanate decreases O2 extraction ratio in dogs

It has been proposed that an increase in the affinity of hemoglobin for O2 may be beneficial in severe hypoxemia. To test this hypothesis, we compared the response to progressive hypoxemia in dogs with normal hemoglobin affinity (P50 = 32.4 +/- 0.7 Torr) to dogs with a left shift of the oxyhemoglobin dissociation curve (P50 = 21.9 +/- 0.5 Torr) induced by chronic oral administration of sodium cyanate. Animals were anesthetized, paralyzed, and mechanically ventilated. The inspired O2 fraction was progressively lowered by increasing the inspired fraction of N2. The lowest level of O2 transport required to maintain base-line O2 consumption (VO2) was 9.3 +/- 0.8 ml.min-1.kg-1 for control and 16.5 +/- 1.1 ml.min-1.kg-1 for the sodium cyanate-treated dogs (P less than 0.01). Other measured parameters at this level of O2 transport were, for experimental vs. control: arterial PO2 19.3 +/- 2.4 (SE) Torr vs. 21.8 +/- 1.6 Torr (NS); arterial O2 content 10.0 +/- 1.2 ml/dl vs. 4.9 +/- 0.4 ml/dl (P less than 0.01); mixed venous PO2 14.0 +/- 1.5 Torr vs. 13.8 +/- 1.0 Torr (NS); mixed venous O2 content 6.8 +/- 1.0 ml/dl vs. 2.3 +/- 0.2 ml/dl (P less than 0.01); and O2 extraction ratio 32.7 +/- 2.8% vs. 51.2 +/- 3.8% (P less than 0.01). We conclude that chronic administration of sodium cyanate appears to be detrimental to O2 transport, since the experimental dogs were unable to increase their O2 extraction ratios to the same level as control, thus requiring a higher level of O2 transport to maintain their base-line VO2 values.     

尖核和杏仁核在脑啡肽和β—内啡肽的释放中的相互作用

The functional relations between nucleus accumbens and amygdala were investigated with intracranial microinjection, push-pull perfusion and radioimmunoassay in the rabbit. Microinjection of morphine 20 micrograms into nucleus accumbens increased the immunoreactive (ir) enkephalin content in amygdala perfusate from a control level of 0.43 +/- 0.43 fmol/0.5 ml (normal saline group) to 61.6 +/- 16.3 fmol/0.5 ml (P less than 0.01); and ir-beta-endorphin content from 1.88 +/- 0.98 fmol/0.5 ml to 4.80 +/- 1.12 fmol/0.5 ml (P less than 0.05). On the other hand, microinjection of morphine into amygdala increased the release of ir-enkephalins (2.41 +/- 1.41 vs 34.6 +/- 8.4, P less than 0.01) and ir-beta-endorphin (1.79 +/- 0.64 vs 5.58 +/- 1.39 P less than 0.05) in the perfusates of N. accumbens. The results indicate the existence of reciprocal reinforcement of opioid release between the two nuclei, which may take part in a putative positive feedback mechanism in the cerebral analgesic system.     

A sensitive radioimmunoassay of alpha human atrial natriuretic polypeptide using monoclonal antibody recognizing human form ring structure

A monoclonal antibody (C351) against alpha human atrial natriuretic polypeptide (alpha hANP) recognizing human form ring structure was established and applied to a radioimmunoassay of plasma alpha hANP. The minimum detectable amount in terms of 10% radioligand displacement relative to zero dose were 0.28 fmol/tube, corresponding to 0.7 fmol/ml in plasma after extraction using Sep-Pak C18 cartridges. When the mean plasma levels at recumbent position in fasted morning were compared in 10 young (less than 30 years) and 10 elderly (greater than or equal to 50 years) healthy subjects taking normal sodium diet, it was slightly higher in the latter (3.2 +/- 0.4 vs 4.7 +/- 0.5 fmol/ml, mean +/- SE, p less than 0.05). After i.v. infusion of hypertonic saline (2.5% NaCl) at a rate of 0.24 ml/kg/min for 20 min in 6 normal subjects (26 to 35 years), it was increased from 4.1 +/- 0.4 to 5.9 +/- 0.7 fmol/ml (p less than 0.01). In 6 patients with essential hypertension (34 to 57 years), it was elevated with high salt intake, i.e. 3.3 +/- 0.3, 3.9 +/- 1.03 and 7.6 +/- 1.5 fmol/ml under 34, 170 and 340 mEq NaCl/day for 7 days, respectively. From these results, the radioimmunoassay of plasma IR-alpha hANP using MAb C351 seems to be quite suitable to detect rather small changes at low plasma concentrations and to investigate a physiological importance of alpha hANP in man.     

Treatment of 80 patients with Turner's syndrome with recombinant human growth hormone (YM-17798) for one year: the results of a multicentric study in Japan. Committee for the Treatment of Turner's Syndrome

A total of 80 patients with Turner's syndrome were treated with methionine-free recombinant hGH (r-hGH) for one year. Thirty-nine patients were treated with r-hGH at weekly dosage of 0.5 IU/kg and forty-one were treated with 1.0 IU/kg/w by daily sc injection. Both treatment groups showed a statistically significant growth increase during the treatment from 3.7 +/- 1.0 to 6.0 +/- 1.1 and 7.2 +/- 1.3 (mean +/- SD) cm/year, respectively. Fifty-nine percent of the patients treated with 0.5 IU/kg/w and 87.8% of the patients treated with 1.0 IU/kg/w showed a growth rate more than 2 cm greater than the pretreatment values. Plasma somatomedin C levels were elevated and no remarkable advances in bone age were observed during the treatment in both treatment groups. An antibody against to hGH was observed in 6.8% of the patients. Otherwise, there were no significant changes in physical or laboratory examinations. No glucose intolerance was observed. These results indicate that hGH treatment is useful in accelerating growth velocity in patients with Turner's syndrome.     

Fluctuation in responsiveness of LH and lack of responsiveness of FSH to prolonged infusion of morphine and naloxone in the ewe

In ewes in the mid-luteal phase, LH pulse frequency (P less than 0.01) and amplitude (P less than 0.05) increased during a 24 h infusion of naloxone (0.5 mg/kg/h) compared to a 24 h infusion of vehicle (mean +/- s.e.m.; 0.25 +/- 0.03 vs 0.14 +/- 0.01 pulses/h and 0.84 +/- 0.08 vs 0.55 +/- 0.08 ng/ml serum, respectively). The increase in pulse amplitude was immediate, but was less (P less than 0.05) during the second 12 h, compared to the first 12 h, of naloxone infusion (0.52 +/- 0.14 vs 0.98 +/- 0.08 ng/ml serum). Oestradiol concentrations were higher (P less than 0.01) during naloxone than during control infusion (5.63 +/- 0.26 vs 4.13 +/- 0.15 pg/ml serum). In ovariectomized ewes in the breeding season, LH pulse frequency was lower (P less than 0.01) during a 24 h infusion of morphine (0.5 mg/kg/h) than during a 24 h infusion of vehicle (mean +/- s.e.m.; 1.17 +/- 0.08 vs 1.71 +/- 0.06 pulses/h). We conclude that long-term infusion of naloxone results in a sustained increase in LH pulse frequency but only a transient elevation in pulse amplitude. No effects on FSH secretion were noted. LH secretion was sensitive to morphine in the absence of ovarian steroids, suggesting that ovarian steroids are not required for the presence of functional opioid receptors capable of modulating LH release.     

Sexual maturation and morphological development of the reproductive tract in large white and prolific Chinese Meishan pigs

Body weight of Large White gilts was greater at birth, weaning, 5 months of age and at slaughter; however, Meishan gilts reached puberty at an earlier age (91 +/- 2 vs 192 +/- 3 days, P less than 0.01), had longer periods of oestrus (60 +/- 2 vs 49 +/- 2 h, P less than 0.01) and experienced more oestrous cycles (7 +/- 0.4 vs 4 +/- 0.4, P less than 0.01) before slaughter. The interoestrous interval was longer (P less than 0.01) for Large White gilts (19.8 +/- 0.2 vs 19.1 +/- 0.2 days). At slaughter, uterine length (P less than 0.05), uterine weight, width of uterine horns, endometrial surface area, endometrial weight and percentage of uterine weight represented by endometrium was greater (P less than 0.01) for Large White gilts. However, breed differences were not significant when slaughter weight was included in analyses as a covariate. This indicated that development of the reproductive tract was proportionate to body weight at slaughter for each breed. When body weight at slaughter was included as a covariate, effects of day of the oestrous cycle and pregnancy on uterine width, uterine weight, endometrial surface area and endometrial weight were detected (P less than 0.01) and for uterine length there was a day-by-status interaction (P less than 0.01). Total number of CL (P less than 0.05) and total ovarian weight (P less than 0.05) were also greater for Large White gilts independent of body weight at slaughter. There were more CL in left ovaries for Meishan (8.1 +/- 0.4 vs 6.6 +/- 0.4) and Large White (8.4 +/- 0.4 vs 7.9 +/- 0.5) gilts.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hyperbaric oxygen toxicity: role of thromboxane.

Exposing rabbits for 1 h to 100% O2 at 4 atm barometric pressure markedly increases the concentration of thromboxane B2 in alveolar lavage fluid [1,809 +/- 92 vs. 99 +/- 24 (SE) pg/ml, P less than 0.001], pulmonary arterial pressure (110 +/- 17 vs. 10 +/- 1 mmHg, P less than 0.001), lung weight gain (14.6 +/- 3.7 vs. 0.6 +/- 0.4 g/20 min, P less than 0.01), and transfer rates for aerosolized 99mTc-labeled diethylenetriamine pentaacetate (500 mol wt; 40 +/- 14 vs. 3 +/- 1 x 10(-3)/min, P less than 0.01) and fluorescein isothiocyanate-labeled dextran (7,000 mol wt; 10 +/- 3 vs. 1 +/- 1 x 10(-4)/min, P less than 0.01). Pretreatment with the antioxidant butylated hydroxyanisole (BHA) entirely prevents the pulmonary hypertension and lung injury. In addition, BHA blocks the increase in alveolar thromboxane B2 caused by hyperbaric O2 (10 and 45 pg/ml lavage fluid, n = 2). Combined therapy with polyethylene glycol- (PEG) conjugated superoxide dismutase (SOD) and PEG-catalase also completely eliminates the pulmonary hypertension, pulmonary edema, and increase in transfer rate for the aerosolized compounds. In contrast, combined treatment with unconjugated SOD and catalase does not reduce the pulmonary damage. Because of the striking increase in pulmonary arterial pressure to greater than 100 mmHg, we tested the hypothesis that thromboxane causes the hypertension and thus contributes to the lung injury. Indomethacin and UK 37,248-01 (4-[2-(1H-imidazol-1-yl)-ethoxy]benzoic acid hydrochloride, an inhibitor of thromboxane synthase, completely eliminate the pulmonary hypertension and edema.(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of pituitary dwarfism with methionyl human growth hormone in Japan

Sixty-two patients with pituitary dwarfism were treated with three different preparations of methionyl hGH (m-hGH) for 3 to 14 months. They were given 0.5 IU/kg/week intramuscularly. The growth rate during treatment with the three different preparations was the same for each and increased from 3.5 +/- 0.9 to 8.2 +/- 1.7 cm/year. A high incidence of hGH antibody formation was observed following the treatment, but the titer of antibody was decreased according to the purity of m-hGH preparations. At the end of 12 month treatment with a highly purified preparation (Somatonorm III), 76.2% of the patients had hGH antibody. However, the presence of antibodies did not affect the growth rate except in one patient. No clinical or laboratory side-effects were observed following the treatment with m-hGH. Thus, m-hGH was considered to be useful for the treatment of GH deficient children.     

Increase in pulsatile secretion of growth hormone during failure of catch-up growth following glucocorticoid-induced growth inhibition

The pattern of growth hormone (GH) secretion was determined in rats injected with cortisone acetate, 5 mg/rat/day subcutaneously, or with an equivalent volume of saline for 4 days from age 40 days. Cortisone injections resulted in inhibition of growth of body weight and tail length. During recovery the rats resumed a normal rate of growth but failed to show catch-up growth acceleration. From 17 to 27 days of recovery, plasma was sampled at 15-min intervals through the lights-on period, 06:00 to 18:00, via a catheter chronically implanted in the superior vena cava. During sampling each rat was housed singly in an insulated chamber, unrestrained, and with food and water ad lib. Cortisone-treated animals had a normal periodicity of GH plasma concentration, but they showed a reduction in values in the range of 50 to 99 ng/ml (P less than 0.01) and an increase of values in the range of 200 to 499 ng/ml (P less than 0.025) and above 1000 ng/ml (P less than 0.05). The area under the GH concentration curve of the cortisone-treated rats was significantly greater than that of the controls, 100.9 +/- 18.7 (mean +/- SE) units vs 55.3 +/- 7.4 (P less than 0.025). Thus, increased growth hormone secretion during the light phase persisted in spite of failure of catch-up growth acceleration. The findings indicate that the mechanism involved in GH release is linked to the catch-up growth control.     

Sex and training differences in human growth hormone levels during prolonged exercise

Human growth hormone (hGH) levels were measured during rest, prolonged treadmill exercise at 60% maximum O2 uptake (VO2max), and immediate recovery in four groups of subjects (n = 7/group), ages 21-30 yr, classified as male runners (MR), female runners (FR), male controls (MC), and female controls (FC) to determine whether sex differences in the hGH response are related to resting 17 beta-estradiol (E2) and/or cardiorespiratory endurance (CRE). Glucose (Glc), E2, and hGH levels were determined from serial blood samples taken from an intravenous catheter. Glc did not change significantly during exercise, but different trends for the runners (increases) vs. controls (decreases) resulted in higher (P less than 0.01) postexercise levels in the runners. Resting hGH was higher (P less than 0.05) in the FRs and FCs than the MRs and MCs, respectively, and continued to be higher in the FCs (vs. MCs) during the first 30 min of exercise. The MRs achieved higher peak hGH levels and exhibited higher values than the MCs throughout exercise and recovery. There were no statistically significant training differences in the females. The strongest predictors for peak hGH were absolute work load and group (runners vs. controls), both of which combined accounted for 32-36% of the variability (P less than 0.01) in hGH response. Significant sex-related variables (sex, resting E2) accounted for 11-19% of the variability in peak or percent change in hGH, with E2 having a positive effect at rest but a negative effect during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diaphragmatic activity is a determinant of postnatal lung growth

To test the hypothesis that activity of respiratory muscles determines regional growth of lung parenchyma, we studied the effects of unilateral diaphragmatic paralysis on contralateral/ipsilateral lung growth in cats and piglets. Five 10- to 12-wk-old cats and five 8-wk-old piglets underwent unilateral diaphragmatic paralysis by thoracic and cervical phrenectomy, respectively. Five to seven weeks after surgery, when the cats were killed for studies of lung growth, gain in body weight was the same as in five sham-operated controls. At this time, mean pleural pressure ipsilateral to the paralyzed hemidiaphragm was the same as contralateral mean pleural pressure during tidal breathing, and values did not differ from controls. However overall functional residual capacity was lower in the phrenectomized cats (35 +/- 4 ml) than in the controls (55 +/- 11 ml, P less than 0.01). Growth of contralateral lungs relative to ipsilateral lungs was greater in the phrenectomized cats than in the controls, as shown by ratios of contralateral/ipsilateral wet lung weight (1.44 vs. 1.34, P less than 0.01), maximum inflation volume (1.53 vs. 1.33, P less than 0.05), and total protein content (1.45 vs. 1.26, P less than 0.05). Ratios of total protein to DNA and RNA to DNA were unchanged. One week after surgery in the piglets, the ratio of contralateral/ipsilateral wet lung weight was increased (1.61 vs. 1.29, P less than 0.01) and total weight of both lungs was reduced. We conclude that regional growth of lung parenchyma by cell proliferation depends in part on regional distribution of respiratory muscle activity.