Peak Growth Hormone Concentrations Research Articles

Intranasal activity of the growth hormone releasing peptide HisDTrpAlaTrpDPheLysNH 2 in conscious dogs

This series of experiments was conducted to evaluate the growth hormone (GH) releasing activity of intranasally administered HisDTrpAlaTrpDPheLysNH 2 (GHRP-6, SK&F 110679) in conscious dogs. Intranasal administration of GHRP-6 increased plasma growth hormone levels in the conscious dog in a dose-related manner. Doses of 0.25 and 0.5 mg/kg produced GH levels of 11.3 ± 4.8 ng/ml and 28.6 ± 8.0 ng/ml, respectively. Peak levels were observed 15 minutes after dosing and GH levels were elevated for up to 105 minutes after intranasal dosing. Intranasal administration of isotonic saline did not produce any change in basal (negligable) GH levels. When GHRP-6 was given by the intravenous route, a maximal dose of 0.5 mg/kg, produced a peak plasma GH concentration of 60.8 ± 10.5 ng/ml. Saline had no effect on GH levels when given intravenously. Using the intravenous and intranasal GH response data (i.e., area under the time-response curves), the intranasal bioavailability of GHRP-6 was estimated to be 34.4 to 44.9%. The results of these studies suggest that significant activity and excellent bioavailability can be achieved when GHRP-6 is administered by the intranasal route to conscious dogs. Based on these results, the intranasal activity of GHRP-6 should be evaluated in man. The successful intranasal administration of this peptide in man should provide GH therapy with reduced patient discomfort and better patient compliance when compared to presently available parenterally administered remedies.

The effect of methyltestosterone on the growth hormone response to the dopamine receptor agonist, apomorphine

1. 1. There is some evidence that androgens affect dopaminergic function in animals and man. We investigated the effect of methyltestosterone (MT) (30 mg po) on the growth hormone (GH) response to the dopamine (DA) receptor agonist, apomorphine (Apo) HCl (0.5 mg sc), in 9 normal men. MT was given 2 hr before Apo. 2. 2. The peak plasma MT concentration was present 1 hr after administration (19.9±19.5 ng/ml: X ± SD): the concentration at 4 hr was 7.2 ± 4.9 ng/ml. At the time of Apo administration, plasma MT varied from 6.0–24.1 ng/ml. 3. 3. There was no significant effect of MT on Apo-GH secretion (interaction F(7, 56) = 1.08: p = NS). The mean individual peak GH concentration after Apo alone was 20.2 ± 11.9 (X ± SD) vs 22.2 ± 9.9 ng/ml when MT preceded Apo (p = NS). 4. 4. These results suggest that exogenous androgens do not affect DA receptor function in males with normal androgenic function. Lack of effect due to an insufficient dose or duration of administration of MT cannot be excluded.

Growth Hormone Release in Response to Growth Hormone-Releasing Hormone in Term and Preterm Neonates

The growth hormone response to a single intravenous dose of human growth hormone-releasing hormone (GHRH) was examined in 23 healthy neonates (12 term and 11 preterm) aged 2-4 days. There were no significant increases in growth hormone concentrations at any point in time studied following GHRH administration in either group of newborns. The mean basal growth hormone levels of term neonates were significantly higher than those of the premature newborns (39.6 +/- 5.3 vs. 23.2 +/- 3.3 ng/ml; p less than 0.01) and this difference in growth hormone remained significant 15 and 30 min after GHRH injection. Gestational age correlated positively with both basal and peak growth hormone concentrations in our patients. In conclusion, first, neonates studied in their first days of life have high basal levels of growth hormone and fail to further secrete any significant amount of growth hormone following a single dose of GHRH, and, second, premature newborns secrete significantly less growth hormone than do term neonates.

99 TREATMENT OF SHORT NORMAL PREPUBERTAL CHILDREN WITH GRWOTH HORMONE

The growth reponse to growth hormone (GH) was studied in 9 short normal prepubertal children (6 boys, 3 girls) with a low height velocity. Their average age was 8.2yr (range 4.7-12.1), height standard deviation score (SDS) for chronological age (CA) was -2.6 (-2.0 to -3.7). All had normal maximum plasma GH responses above 10ng/mL to stimulation with clonidine and/or insulin induced hypoglycemia. Assessment of overnight GH secretion by measurement of GH in 20min intervals for 12h yielded low peak levels of 8.7±3.0(SD)ng/mL and low mean pool values of 1.9±1.0. With informed consent treatment with somatrem (Protropin) 0.11±0.01mg/kg three times weekly s.c. was then begun and continued for one year. No major side effects were noted. After 6 months of GH therapy, height velocity SDS for CA increased significantly (p<0.001) from a pretreatment mean of -1.7 (-0.6 to -3.0) to +3.4 (-1.0 to +5.7), representing a change from 4.7cm/yr (3.5-6.0) to 9.3 (5.7-12.5). Height velocity during GH treatment (SDS for CA and cm/yr) inversely correlated with endogenous nocturnal peak GH concentration (r=-0.76, and r=-0.78; both p<0.05). We conclude that some short normal children with low height velocity and low endogenous GH secretion may profit from GH therapy. A major goal should be the proper identification of these patients and careful long-term follow-up to final height. Supported by Genentech, Inc., South San Francisco, California.

A persistent pattern of varying pituitary responsivity to exogenous growth hormone (GH)-releasing hormone in GH-deficient children: evidence supporting periodic somatostatin secretion.

The pattern and degree of variation in pituitary responsivity to GHRH was examined in four GH-deficient children (two boys and two girls, aged 4 3/12 to 10 4/12 yr). All children were studied before and on multiple (three to six per child) occasions during long term GHRH therapy (1 or 2 micrograms/kg, sc, every 3 h) in an identical fashion. Each study comprised withdrawal of blood for serum GH measurements every 20 min between 2000 and 0800 h. All subjects received GHRH at 2000, 2300, 0200, and 0500 h as well as at 0800, 1100, 1400, and 1700 h throughout the long term treatment period (6-18 months). Although all children had low level (less than 7.0 micrograms/L) pulsatile GH secretion during baseline studies, the maximal peak values occurred at times other than 0500 h. Before GHRH treatment, serum GH levels rose significantly in response to 91% (62 of 68) of the GHRH doses administered. GH pulse amplitudes varied throughout the studies in all children, and this variability persisted despite 1300-3600 consecutive doses in each child. In all 17 study periods the highest serum GH concentration occurred shortly after the 0500 h GHRH dose. The mean peak GH concentration after the 0500 h GHRH dose [18.4 +/- 3.5 (+/- SE) micrograms/L] was significantly higher than those after the 2000 h (5.3 +/- 1.0 micrograms/L; P = 0.0001), 2300 h (7.4 +/- 2.1 micrograms/L; P = 0.0003), and 0200 h (10.9 +/- 2.5 micrograms/L; P = 0.011) doses. These results demonstrate that the responsivity of the pituitary to GHRH varies throughout the night in some GH-deficient children. There appears to be a direct relationship between the time of night and the degree of pituitary responsivity to GHRH. We suggest that this variable responsivity may be due to intermittent hypothalamic somatostatin secretion.

Effects of insulin-like growth factor I (IGF-I) on growth hormone-releasing factor (GRF) and thyrotropin-releasing hormone (TRH) stimulation of growth hormone (GH) secretion in the domestic fowl ( Gallus domesticus)

Recent studies in mammalian species indicate that IGF-I may act as a negative feedback inhibitor of GH release through alteration of pituitary secretion or sensitivity to hypothalamic regulatory factors. Although avian GH secretion appears to be regulated by the differential release of hypothalamic inhibitory (somatostatin) and stimulatory (GRF and TRH) factors, feedback effects of IGF-I on in vivo GH release in birds have not been investigated. To study the effects of elevated IGF-I concentration on GRF- and TRH-stimulated GH secretion, 4-week-old chickens received an intravenous injection of recombinant human IGF-I either 15 min prior to (6 μg, study 1), or simultaneous with (10 μg, study 2), GRF (hGRF44NH 2, 5 μg/kg) or TRH (0.5 μg/kg) administration. Radioimmunoassay analysis of plasma collected prior to and following peptide treatment indicated that circulating IGF-I concentrations were elevated 83.9, 60.6, 77.9, and 88.8% at the time of TRH and GRF administration in studies 1 and 2, respectively. Peak GH concentrations (mean of +5- and +15-min samples) subsequent to TRH injection were significantly ( P < 0.01) depressed 45.1 and 48.2% in IGF-I-treated as compared with control chicks in the first and second studies, respectively. GRF-stimulated GH secretion was significantly ( P < 0.01) decreased by IGF-I administration in study 2 (41.3%) but not in study 1. An estimated half-life for IGF-I in the chicken is less than 15 min based on the disappearance rate of the elevation produced by exogenous IGF-I injections. Thus, IGF-I exerts a negative feedback effect on pituitary hormone secretion in avian as well as mammalian species.

Selective β1-adrenergic receptor-blockade with atenolol enhances growth hormone releasing hormone and mediated growth hormone release in man

The growth hormone (GH) responses to a single bolus injection of the growth hormone releasing hormone (GRH) were examined in the basal state and in the presence of β-adrenergic receptor blocking agents of different specificity in ten normal men. During a constant five-hour infusion of 56 μg/min of propanolol (nonselective β-adrenergic receptor-blocker) in seven subjects studied, there was a significant augmentation of the GH release in response to exogenous GRH compared to the GH response during saline infusion, as measured by the peak serum GH concentrations after GRH ( P = 0.019) and the integrated GH values ( P = 0.019). A similar significant enhancement of GH responses to exogenous GRH as compared to the control day was observed with the specific β 1-adrenergic receptor-blocker atenolol in all seven subjects studied (four of whom also participated in the propanolol study). Both the peak GH response to a GRH bolus and the integrated GH values were significantly greater with atenolol ( P = 0.019 for both). There was no difference in serum GH concentrations after β-adrenergic receptor-blocking drugs during a three-hour sampling period before GRH administration compared to placebo. Our results support the concept that β-adrenergic receptors may modulate either the release or action of hypothalamic somatostatin in the control of GH secretion in man. We suggest the effect is mediated by specific β 1-adrenergic receptors.

Growth hormone (GH) provocative testing frequently does not reflect endogenous GH secretion.

GH secretion was studied in 73 children with classical GH deficiency or GH neurosecretory dysfunction (GHND), intrinsic short stature, or normal stature. The GH-deficient group was defined by a peak GH secretory response below 10 ng/ml to all provocative tests (arginine, L-dopa, insulin hypoglycemia, and clonidine). GHND was defined by a mean serum 24-h GH concentration below 3 ng/ml, with a normal response (greater than or equal to 10 ng/ml) to provocative testing. Twenty-one GH-deficient children, 21 children with GHND, and 18 short control children underwent provocative GH testing and a 24-h study with GH sampling every 20 min. A group of 13 normal stature control children also underwent 24-h GH sampling. The mean stimulated peak serum GH level [4.7 +/- 0.6 (+/- SEM) ng/ml] in the GH-deficient group was significantly below that in the GHND (19.5 +/- 1.7 ng/ml) and short control groups (24.0 +/- 3.5 ng/ml; P less than 0.01). The mean 24-h serum GH concentration was reduced in GH-deficient (1.5 +/- 0.2 ng/ml) and GHND (2.0 +/- 0.1 ng/ml) children compared to those in short (5.6 +/- 0.5 ng/ml) and normal stature (5.8 +/- 0.8 ng/ml) control children (P less than 0.01). Peak GH concentrations after provocative testing correlated poorly with 24-h mean concentrations in GH-deficient, GHND, and short control children (r = 0.38, 0.23, and 0.41, respectively; P = NS for all groups). Mean serum GH concentrations from blood sampling intervals of 12 h (day/night; 0800-2000/2000-0800 h, respectively) or even 6 h (day; 0900-1500 h) were statistically different in GHND or GH-deficient groups compared to those in control children; however, there was significantly more overlap for individual children using the 6- and 12-h daytime intervals than for the 24-h data. Plasma somatomedin-C/insulin-like growth factor I correlated with mean 24-h GH concentration endogenous secretion (r = 0.7; P less than 0.001). These data suggest that provocative GH testing frequently does not correlate with endogenous GH secretion.

Continuous infusion of growth hormone-releasing factor: effects on pulsatile growth hormone secretion in normal rats.

The effects of a continuous infusion of growth hormone-releasing factor (GRF) on pulsatile growth hormone (GH) secretion were studied in conscious, freely moving rats. Male Sprague-Dawley rats were prepared with 2 indwelling venous catheters and were then housed individually for 6-16 days in isolation chambers. After this period, normal saline, 1.5 microgram/h GRF or 15 micrograms/h GRF were continuously infused for 8 or 31 h via one of the catheters. Blood samples were drawn at approximately 20-min intervals via the other catheter during the last 6-7 h of the infusion. Plasma GH concentrations were determined by RIA. Saline-treated animals exhibited the typical pattern of spontaneous GH pulses. The frequency of GH pulses in animals infused with either dose of GRF was not different from that of the saline-infused rats. Likewise, trough GH concentrations were similar in all three treatment groups. However, peak GH concentrations in the rats receiving the 15-micrograms/h GRF infusion were remarkably higher than the concentrations observed in the other two groups, regardless of the duration of the infusion. This resulted in mean GH concentrations being significantly higher (p less than 0.01) in the 15-micrograms/h GRF-infused rats. These results demonstrate that pituitary episodic GH secretion continues even in the presence of a continuous GRF stimulation.

COMPARISON BETWEEN A PHYSIOLOGICAL AND A PHARMACOLOGICAL STIMULUS OF GROWTH HORMONE SECRETION: RESPONSE TO STAGE IV SLEEP AND INSULIN-INDUCED HYPOGLYCAEMIA

Peak growth hormone (GH) response to insulin-induced hypoglycaemia was compared with peak GH concentration during the first cycle of stage IV sleep in 75 children. 65 children had concordant results: in 38 GH concentrations were greater than 15 mU/l and in 27 less than this value. Results were discordant in 10 children. Results of sleep sampling under electroencephalographic control for the assessment of GH secretion are comparable to conventional pharmacological studies in terms of efficiency, sensitivity, and percentage false-negatives. Sleep sampling has the advantage of being a physiological test of secretion.

Variations of plasma growth hormone (GH)-releasing factor levels during GH stimulation tests in children.

GH-releasing factor (GHRH) was measured by RIA in the plasma of 22 constitutionally short children given an ornithine infusion or an oral dose of L-dopa. After an overnight fast and 1 h of rest, plasma GHRH levels were 49.7 +/- 7.3 pg/ml (+/- SEM). In 5 children, L-dopa induced an increase in mean GH levels from 1.8 to 12 ng/ml at 60 min. Mean plasma GHRH levels increased from 47 pg/ml to a peak of 96 pg/ml at 15 min (P less than 0.02). In 4 other children, no increase in either GH or GHRH occurred after L-dopa treatment. In these 9 children, a significant correlation was found between the peak GH and GHRH concentrations (r = 0.841; P less than 0.001). On the contrary, ornithine-induced GH release was not preceded by a GHRH rise, but was followed by a GHRH decrease, from 51 to 27 pg/ml (P less than 0.02). We conclude that the 2 tests stimulate GH release in different ways, and that GH levels may be involved in the feedback control of GHRH secretion.

Growth Hormone Responses to Sleep, Insulin Hypoglycaemia and Arginine Infusion

This study compares the peak serum growth hormone (GH) concentration during slow wave sleep with the serum GH responses to insulin-induced hypoglycaemia and intravenous arginine infusion in 23 children referred because of short stature (20) or precocious puberty (3). Peak serum GH concentration during sleep correlated significantly with peak GH response to insulin hypoglycaemia (r = 0.64, p less than 0.01) and arginine infusion (r = 0.57, p less than 0.01). 3 children had subnormal (less than 15 mU/l) peak serum GH concentrations during sleep but normal responses to either insulin-induced hypoglycaemia or intravenous arginine infusion. 1 child had a normal peak serum GH response to sleep but subnormal responses to insulin and arginine. Sleep studies of GH secretion may be indicated when the GH responses to pharmacological stimuli are inconsistent with the observed growth pattern.

Effect of growth hormone (GH)-releasing hormone (GRH) on plasma GH in relation to magnitude and duration of GH deficiency in 26 children and adults with isolated GH deficiency or multiple pituitary hormone deficiencies: evidence for hypothalamic GRH deficiency.

Synthetic, amidated, 44 amino acid GH-releasing hormone ( GRH -44) was administered iv at a dose of 5 micrograms/kg to 20 patients with severe GH deficiency (GHD), 6 children and adolescents with partial GHD, and 6 non-GH deficient ( NGHD ) children and adolescents. The 17 patients with severe GHD that responded to GRH -44 had lower peak concentrations of plasma GH than the NGHD individuals (5.0 +/- 1.2 (SEM) vs. 27.2 +/- 3.5 ng/ml; P less than 0.0001). The children and adolescents with severe GHD tended to have higher peak GH responses to GRH -44 than the GHD adults (6.9 +/- 1.7 vs. 2.4 +/- 0.3 ng/ml) although the difference was not significant. The peak GH concentration was attained earlier in the GHD children and adolescents than in the GHD adults (28 +/- 4.7 vs. 69.3 +/- 13 min, P less than 0.004). There was a negative correlation between chronological age and peak plasma GH response to GRH in the children and adolescents with severe GHD (r = -0.758, P less than 0.02). Children and adolescents with partial GHD had a higher mean peak concentration of plasma GH (13. 1 +/- 1.8 ng/ml) than the children, adolescents, and adults with severe GHD (P less than 0.04), but one lower than the NGHD children and adolescents (P less than 0.05). In both severe and partial GHD the GH response to GRH was greater than that elicited by standard pharmacological tests. Serum somatomedin-C did not increase after a single pulse of GRH -44 in the 12 GHD patients studied. PRL increased minimally 30 min after 5 micrograms/kg iv GRH -44 in patients with multiple hypothalamic-pituitary hormone deficiencies but not in patients with isolated GHD or in NGHD individuals. The GH responses to GRH suggest that the majority of patients with isolated GHD as well as those with multiple hypothalamic-pituitary hormone deficiencies have deficiency of hypothalamic GRH . Lack of a GH response to a single pulse of GRH does not exclude GRH deficiency as priming of the somatotrope with multiple pulses of GRH may be necessary to rule out a hypothalamic defect in the nonresponders. The results of this study support the potential usefulness of GRH or its analogs in the diagnosis and treatment of selected patients with disorders of GH secretion.

PREVALENCE OF GROWTH HORMONE DEFICIENCY IN CHILDREN WITH CLEFT LIP/PALATE (CLP)

The prevalence of growth hormone (GH) deficiency in the general population is about one in 3,000-4,000 or one per cent in children who are below the third percentile for height. Rudman et al reported a prevalence of 32% in short children with CLP (J Pediatrics 93:378, 1978). The criterion used was an average peak concentration of GH. Since this reported prevalence is strikingly high, we examined the records of 373 children who were on the active files of our CLP Clinic.Of these, 40 patients with overt CLP (21 CL&CP, 18 CP, 1 CL) were at or below the 5th percentile for height. In this group of 40, 12 had multiple congenital anomalies or clearly defined syndromes. Fourteen had familial short stature and were growing at a normal rate for height. Of the remaining 14 children (8 boys, 6 girls, mean age 6.2 years) two were lost to follow up and two refused endocrine evaluation. None of the remaining 10 had growth hormone deficiency.Using the standard criteria of impaired growth rate and lack of response to arginine-insulin provocative test (peak less than 5 ng/ml) we were unable to document that a single patient in this group had GH deficiency. Clearly our findings are discordant with those reported by Rudman et al. A possible reason may be that different criteria were used for diagnosing GH deficiency.

Effect of L-tryptophan on apomorphine-induced growth hormone secretion in normal subjects.

Oral administration of the serotonin precursor, L-tryptophan, to normal male volunteers (n = 7) in a dose (3 g) sufficient to increase free plasma tryptophan concentrations more than 12-fold had no significant effect on basal growth hormone secretion or on apomorphine HCL-induced (0.75 mg sc) peak growth hormone concentrations. These data suggest that, in man, tryptophan administration has little effect on central dopaminergic function, at least in the hypothalamic-pituitary axis and that serotonergic mechanisms have no major modulatory effect on dopamine-mediated growth hormone secretion.

Growth hormone, glucocorticoid and thyroxine response to duration, intensity and wavelength of light in prepubertal bulls.

Effects of duration, intensity and wavelength of light on growth hormone (GH), glucocorticoids, thyrotropin (TSH) and thyroxine (T4) concentrations in serum were determined in prepubertal bulls maintained at 18 to 22 C and 60 tp 70% relative humidity. Mean GH was 8.3 +/- .8, 9.5 +/- 2.2 and 13.8 +/- 2.2 ng/ml (P greater than .10) during 6 weeks of exposure to 8 hr of light: 16 hr of dark (8L:16D), 16L:8D and 20L:4D, respectively. However, concentrations of GH were more variable (P less than .01) in bulle exposed to 16L:8D and 20L:4D than in bulls exposed to 8L:16D. Concentrations of GH averaged 10.6 +/- 1.3 and 13.6 +/- 2.6 ng/ml (P greater than .10) when intensities of light exposures were 22 and 540 lux. Variability of GH was greater (P less than .01) in bulls exposed to 540 lux. Increase in the duration of light by the addition of 8 hr of red (550 to 750 nm) or 8 of blue (300 to 427 nm) light to 8 hr of white (300 to 750 nm) light did not affect (P greater than .10) mean GH concentrations. Among experiments, concentrations of glucocorticoids decreased by 29 to 58% (P less than .05) when daily light exposures were increased from 8 to 15.7, 16 or 20 hours. Conversely, glucocorticoids increased by 118% (P less than .05) when light was decreased from 15.7 to 8 hr daily. Duration of light exposures did not effect concentrations of TSH or T4. Similarly, intensities of 22 and 540 lux and blue and red wavelengths of light did not affect average concentrations of glucocorticoids or T4. Injection of 33 microgram thyrotropin releasing hormone (TRH)/100 kg body weight increased (P less than .05) GH two- to five-fold above average basal values; however, duration, intensity and wavelength of light did not influence peak GH concentration or area of GH response curves after injection of TRH. We conclude that in comparison with 8 L, 16 L increased variance of GH without affecting average concentrations of GH, TSH or T4. In contrast, 16 L suppressed serum glococorticoids.

Somatomedin and Growth Hormone Studies

Plasma somatomedin (SM) activity and growth hormone (GH) concentration were measured in ten growth-retarded, well-nourished pediatric renal allograft recipients who received daily prednisone therapy. The SM activity ranged from 0.21 to 1.22 micron/mL, and it was subnormal in three patients. A significant correlation was found between SM activity and creatinine clearance. Serial SM levels were determined during a 24-hour period in five patients; SM activity decreased at six and 12 hours and returned to normal values by 24 hours. The 24-hour plasma GH concentrations ranged from 1.5 to 7.6 mg/mL. Peak GH concentrations ranged from 2.1 to 14.2 ng/mL after insulin-induced hypoglycemia and from 1.8 to 24.6 ng/mL after oral glucose loading. Sleeping GH peaks were absent in two patients. These results suggest that growth failure in renal allograft recipients who receive daily prednisone may result from (1) partial GH deficiency, (2) reduced SM levels owing to diminished allograft function, and (3) daily transient decrease in plasma SM levels after prednisone administration.

Effect of apomorphine on growth hormone and prolactin secretion in schizophrenic patients, with or without oral dyskinesia, withdrawn from chronic neuroleptic therapy.

Serum growth hormone (GH) and prolactin (PRL) concentrations were measured after administration of the dopamine receptor agonist, apomorphine HC1 (0.75 mg subcutaneously), to 17 chronic schizophrenic patients, four of whom had an oral dyskinesia, who were withdrawn from chronic neuroleptic therapy for periods of two to 15 weeks, and in 21 control subjects (normal volunteers or physically healthy alcoholics not exposed to neuroleptics). Six of the schizophrenic patients, but none of the controls, had raised baseline levels of GH (greater than 6 ng/ml). After apomorphine all controls showed an increase in serum GH with a peak concentration of 9 ng/ml or more, whereas eight subjects withdrawn from neuroleptics showed an inadequate response (peak less than 6 ng/ml) and in two others an inadequate response was obtained on one of two trials. The peak GH concentration was significantly less after apomorphine in patients withdrawn from neuroleptics (11.90 +/- 3.19 ng/ml) compared with controls (20.80 +/- 2.11 ng/ml) (P less than 0.05). Among patients withdrawn from neuroleptics, those with an oral dyskinesia had significantly lower peak GH concentration 2.46 +/- 0.93 ng/ml) after apomorphine compared with those without (14.85 +/- 3.83 ng/ml) (P less than 0.05). There were no differences in serum PRL concentrations, before or after apomorphine administration, between patients withdrawn from neuroleptics and controls. In uncontrolled observations none of the four patients with an oral dyskinesia showed any worsening of the movement disorder after apomorphine. These data provide no evidence for supersensitivity of dopamine receptors in chronic schizophrenic patients withdrawn from chronic neuroleptic therapy.

Effect of l-dihydroxyphenylalanine upon serum growth hormone concentrations in children and adolescents

Serum growth hormone levels were measured serially in 26 children and adolescents, two adult males, and four patients with Parkinson's disease after oral administration of 0.5 Gm. of l -dihydroxyphenylalanine ( l -dopa); the results were compared to those obtained after administration of arginine and insulin. In 22 children without pituitary disease the mean maximum growth hormone concentration (8.9±1.5 [S.E.M.] mμg per milliliter) was recorded 60 minutes after l -dopa ingestion. The mean peak growth hormone concentrations was 11.2±1.4 mμg per milliliter; the mean increment was 10.1±1.4 mμg per milliliter. During a combined arginine-insulin tolerance test (N=19) the mean peak growth hormone value was 13.4±1.3 mμg per milliliter; the mean increment was 11.9±1.2 mμg per milliliter. Growth hormone levels did not increase in four patients with hypopituitarism following administration of l -dopa, arginine, or insulin. Growth hormone concentrations increased in both adult males and in one of four patients with Parkinson's disease after administration of l -dopa. Variable changes in blood glucose and insulin concentrations followed l -dopa ingestion. l -dopa stimulates the release of growth hormone in young subjects without pituitary disease.

Diabetic Ketosis: Serial Plasma Growth Hormone Concentrations During Therapy

Plasma growth hormone (GH) concentrations were measured serially during therapy in twelve cases of diabetic ketosis. The initial plasma GH levels varied widely, ranging from 2 to 215 ng./ml., and were not related to the clinical severity of the ketosis, the degree of depression of the serum bicarbonate, or the magnitude or the hyperglycemia. An increase in the plasma GH concentration followed the institution of insulin therapy in ten of twelve cases. This rise was associated with a fall in the plasma glucose concentration though the latter reached hypoglycemic levels in only one instance. There was no relationship between the total insulin administered during the first twelve hours of therapy and the area under the GH curve for the same period or the initial or peak plasma GH concentration. Thus, despite its known diabetogenic effect and the frequent occurrence of elevated plasma concentrations in ketotic diabetics, growth hormone cannot be a constant major determinant of the insulin resistance of diabetic ketosis.