Pulsatile Pattern Of Growth Hormone Secretion Research Articles

The Impact of Short-Term Fasting on the Dynamics of 24-Hour Growth Hormone (GH) Secretion in Patients with Severe Radiation-Induced GH Deficiency

In patients with severe radiation-induced GH deficiency, we previously demonstrated that pulsatile GH secretion and diurnal rhythm are maintained in the fed state, albeit with great attenuation of the pulse amplitude. However, it remained unclear whether stressing the hypothalamic-pituitary axis could unmask neurosecretory dysregulation that is not seen under basal conditions. In addition, the impact of fasting on GH pulsatility and diurnal variation in GH-deficient patients has not been studied in detail before. STUDY SUBJECTS AND DESIGN: Twenty-four-hour GH profiles at 20-min intervals were undertaken in the fed state and in the last 24 h of a 33-h fast in eight young adult cancer survivors (two women) with severe GH deficiency after cranial irradiation for nonpituitary brain tumors in childhood and 14 matched normal controls (three women). A sensitive chemiluminescence GH assay was used with cluster analysis. Fasting induced a significant (P < 0.05) rise in all amplitude-dependent measures (absolute GH peak and nadir, profile mean GH, and mean pulse amplitude and area) in both groups. Pulse frequency was nonsignificantly increased (by 10%) in normals but significantly increased (by 20%) in the patients. The average increase in the individual fasting profile mean GH concentration was 3.7-fold (range 1.5-8.3) in normals, compared with 2.7-fold (range 1-4.7) in the patients (P > 0.05). Fasting amplified amplitude-related differences between patients and controls, and thus, unlike in the fed state, the day (0900-2040 h) mean GH completely demarcated patients from normals. An absolute GH peak level of 2 and 4 microg/liter and a profile mean GH level of 0.25 and 0.65 microg/liter completely separated patients from normals in the fed and the fasting states, respectively. Overall, fasting seems to induce a feminized pattern of GH secretion with relatively higher interpeak levels, preserved but diminished diurnal variation, and increased secretory disorderliness (increased approximate entropy scores). The overall pulsatile pattern of GH secretion during fasting in patients with radiation-induced GH deficiency and the relative augmentation in GH release are similar to that seen in normals emphasizing that GH neuroregulation is preserved in these patients even when the hypothalamic-pituitary axis is under physiological stress.

Growth hormone and growth hormone-related mRNA in uremic rats: effect of a growth hormone secretagogue.

In experimental animals, the decreased growth during mild uremia is not accompanied by a loss in the capacity of the pituitary gland to secrete growth hormone (GH). With the development of orally administered GH "secretagogues" (GHS), it might be possible to stimulate growth during uremia without injections. This study was designed to determine the effects of the GHS, L-163,255. Uremia was induced by 5/6 nephrectomy (NX). GHS was given orally, 3 mg/kg, twice a week. Four groups of animals included: (1) sham-operated, (2) sham-operated, pair-fed, (3) uremic (NX), and (4) uremic, GHS-treated (NX+GHS). Blood sampling was conducted via intra-atrial catheters, and GH was quantitated. Pituitary GH mRNA was measured by Northern blot, and liver GH receptor and insulin-like growth factor-I mRNAs by RNAase protection. Untreated NX animals had a specific decrease in the "mass" of the GH pulses. A burst of GH was induced by GHS, but the pulsatile pattern of GH secretion over 6 h was not affected. An increase or a return to non-uremic levels of GH-related mRNAs occurred after GHS. Thus, GHS stimulated an acute burst of GH secretion and increased specific mRNAs encoding GH-related proteins in uremic animals.

Growth Hormone Releasing Hormone Treatment in Normal Aging

Because the aging pituitary remains responsive to stimulation by growth hormone (GH) secretagogues - GHRH, ghrelin, and their mimetics - these compounds could potentially be used instead of GH itself to increase GH secretion in aging. The factors contributing to the age-related decline in GH secretion are largely extrapituitary, and with repeated or continuous administration GHS's can significantly increase GH secretion and elevate levels of insulin-like growth factor-I (IGF-I) to the young adult normal range. Treatment with GHS's has both theoretical and practical potential advantages over GH - preserving feedback regulation by IGF-I to buffer against overtreatment, and yielding a more physiologic pulsatile pattern of GH secretion. Nonpeptide GHS's can also be administered orally. This review focuses primarily on results using GHRH; studies with ghrelin agonists are reviewed in detail in other articles from this symposium. We and others have shown that GHRH stimulates the brisk release of GH in healthy seniors, and that repeated administration of GHRH elevates IGF-I in a dose-dependent manner. In two 6-month treatment studies in healthy older women and men, subcutaneous injections of GHRH(1-29)NH2, self-administered once nightly, chronically increased nighttime GH secretion and produced sustained elevations of IGF-I levels. IGF-I increases were greatest in men, averaging 30%. Women not taking estrogen showed somewhat lesser increases (23%), and women taking oral estrogen replacement had no significant increase despite the greatest increments in GH secretion. Lean body mass increased; body fat was reduced by an average of 5-8%, with greatest effect on abdominal visceral fat; and again this effect was blunted in estrogenized women. Effects on physical function varied by group. In nonestrogenized women, physical function deteriorated in those receiving placebo; some measures were stabilized in women receiving GHRH. These changes were not significant in estrogenized subjects. GHRH appeared to improve cognitive function, especially in domains sensitive to changes in processing speed. The formulation of GHRH used in these studies is short-acting, with effects ending within a few hours. Perhaps for this reason, late-night GH secretion decreased after the initial GHRH-stimulated surge, and sleep quality was not improved. Side effects were those of fluid retention and were generally mild. The duration of these studies do not allow inferences to be drawn on prevention of the onset of clinical features of frailty. Thus, 6-month treatment with once-daily GHRH can elevate GH secretion and IGF-I, and improve body composition in a manner similar to the effects of GH. Effects on physical function are equivocal. Effects on cognition are encouraging but preliminary. The current GHRH formulation is too short-acting to provide optimal effects.

Plasma concentrations of growth hormone and insulin-like growth factor-I in chickens developing tibial dyschondroplasia

The concentrations of plasma growth hormone ( GH) and insulin-like growth factor-I ( IGF-I) were measured in broilers during the initial development of tibial dyschondroplasia. Chicks were fed a standard starter ration, or a diet imbalanced in calcium and phosphorus to increase the incidence of dyschondroplasia. At 14 days of age four blood samples were collected and assayed for GH and IGF-I. The chicks were killed at three weeks of age and sections of bone were assessed histologically for evidence of dyschondroplasia. All the chicks displayed a pulsatile pattern of GH secretion. Eight of the group fed the imbalanced diet developed dyschondroplasia which was accompanied by a significant increase in the mean and peak GH concentrations compared with the control group but no increase in basal concentrations. The chicks fed the imbalanced diet which did not develop dyschondroplasia were not different from the control birds. There were no differences in IGF-I concentrations between the groups.

Growth Hormone Secretion in Children with Normal Variants of Short Stature

Pulsatile growth hormone (GH) secretion plays a central role in human growth during the prepubertal period of life. In order to investigate whether or not short stature in prepubertal children with normal variants of short stature (NVSS) may be explained, at least in part, by the presence of abnormalities in the pulsatile pattern of GH secretion, we have studied the spontaneous secretion of GH/24 h in 139 prepubertal children with short stature (< or = -2 SD) and normal growth velocity (> -1 SD) and in 37 prepubertal children with normal height and growth velocity. All of the subjects included in this study exhibited a body mass index (BMI) lower than 1 SD. The patients with short stature were divided into three groups according to their bone age and the existence of familial antecedents of short stature. These groups were: (1) familial short stature without bone age retardation (FSS-1); (2) constitutional, nonfamilial short stature, with bone age retardation suggesting further delay of puberty (possible constitutional delay of growth and puberty), and (3) familial short stature with bone age retardation (FSS-2). Spontaneous GH secretion was analyzed by using a computerized mathematical algorithm of pulsatility (Cluster). In addition, in all of the patients with short stature, the GH secretory response to three different pharmacological stimuli was evaluated, including: clonidine, growth hormone-releasing hormone (GHRH) and hypoglycemia after insulin administration. The mean values of GH/24 h exhibited a wide range of distribution (1.4-7.8ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Ultradian Rhythm of Growth Hormone Secretion in Unrestrained, Conscious Male Rabbits: Role of Endogenous Somatostatint†

Abstract The profiles of growth hormone (GH) secretion were examined by obtaining serial blood samples every 15 min for a 5 to 24 h observation period from freely-moving, conscious male rabbits chronically implanted with a right atrial cannula. The effects of restraint or surgical stress on GH secretion were also investigated in these animals. Four days after cannulation of the right atrium, plasma GH levels remained low without oscillation, during a 5 h observation period (1100 to 1600 h) with the mean (+/- SEM) value of 1.6+/-0.2 ng/ml. Individual rabbits exhibited a spontaneous, pulsatile GH secretion 7 days after the surgery. Mean 6 h GH levels were 5.6 +/- 0.8 ng/ml at 7 days after the surgery, 6.3 +/- 0.6 ng/ml at 14 days and 7.0 +/- 1.2 ng/ml at 28 days. Therefore, the animals, 7 to 14 days after cannulation, were used to analyse the pulsatile pattern of GH secretion throughout 6 to 24 h. Two episodes of 45 min immobilization stress, separated by 75 min, caused a complete suppression of the spontaneous GH secretion (mean 6 h GH levels, 2.2 +/- 0.1 ng/ml vs control, 5.0 +/- 0.5 ng/ml, P<0.01). No surges appeared after the first restraint stress. In 14 non-treated rabbits, plasma GH levels fluctuated in an episodic manner throughout the study with the peaks of 14.2 + 0.7 ng/ml, the nadirs of 2.6 +/- 0.2 ng/ml and the peak to peak intervals of 2.20 +/- 0.17 h. The iv administration of normal goat lambda-globulin (NGG) affected neither GH secretory patterns nor baseline levels of plasma GH. In contrast, the iv administration of anti-sornatostatin goat lambda-globulin (ASG) caused a significant increase in the amplitude of plasma GH peaks (38.8+/-1.9 vs NGG-treated, 13.7 +/- 0.8 ng/ml, P<0.001) as well as the trough level (13.5 +/- 0.6 vs NGG, 2.9 +/- 0.1 ng/ml, P<0.001) during a 24 h observation period. Also, ASG treatment increased numbers of plasma GH peaks per day (18.8+/-2.7 vs NGG, 12.2 +/- 0.8, P < 0.05) with concomitant shortening of the peak to peak interval (1.25 +/- 0.10 vs NGG, 2.03+/-0.12h, P<0.01). These findings suggest: 1) that GH is episodically secreted throughout the day in conscious male rabbits, 2) that surgical and restraint stresses suppress the spontaneous GH secretion, and 3) that endogenous somatostatin might rather play a tonic inhibitory role in GH release in conscious male rabbits, since ASG treatment resulted in sustained marked increases of plasma GH levels irrespective of the stage in GH pulsatile rhythm.

Fasting enhances growth hormone secretion and amplifies the complex rhythms of growth hormone secretion in man.

Studies in man have shown that the episodic release of growth hormone (GH) is infrequent and erratic, and unlike that in the rat does not appear to have discernible ultradian periodicities. However, these observations in nonfasted subjects may be invalid since mixed nutrients have unpredictable effects on GH release. Moreover, in the fed state basal GH levels are frequently undetectable, thus rendering the identification of low amplitude pulses unreliable. Accordingly, the 24-h pulsatile pattern of GH secretion obtained from repetitive venous sampling in six normal adult male subjects was examined during a control fed day and during the first and fifth days of a 5-d fast. The GH data were analyzed using two distinct methods: a discrete pulse detection algorithm (Cluster analysis) and Fourier expansion time-series, which allows fixed periodicities of secretory activity to be resolved. The 5-d fast resulted in a significant increase in discrete GH pulse frequency (5.8 +/- 0.7 vs. 9.9 +/- 0.7 pulses/24 h, P = 0.028), 24 h integrated GH concentration (2.82 +/- 0.50 vs. 8.75 +/- 0.82 micrograms.min/ml; P = 0.0002), and maximal pulse amplitude (5.9 +/- 1.1 vs. 12.3 +/- 1.6 ng/ml, P less than 0.005). While multiple low-amplitude sinusoidal periodicities were present on the control fed day, time-series analysis revealed enhancement of circadian and ultradian cycles on the first and fifth days of fasting. Concomitantly, fasting resulted in a decline (day 1 vs. day 5) in serum concentrations of somatomedin C (1.31 +/- 0.22 vs. 0.77 +/- 0.18 U/ml) and glucose (4.9 +/- 0.2 vs. 3.2 +/- 0.2 mmol/liter), and a marked rise in free fatty acid (0.43 +/- 0.12 vs. 1.55 +/- 0.35 mmol/liter) and acetoacetate (35 +/- 6 vs. 507 +/- 80 nmol/liter). We conclude that the acute nutritional status is an important determinant of spontaneous pulsatile GH secretion in man. Fast-induced enhancement of GH release is achieved through combined frequency (discrete pulses) and amplitude (sinusoidal periodicities) modulation. Such alterations in somatotropic hormone release may play an important role in substrate homeostasis during starvation.

Pulsatile secretion pattern of growth hormone in turkeys: Effects of age and sex

Male and female turkeys were cannulated through the jugular vein, and blood samples were withdrawn remotely at 10-min intervals for a period of 8 hr at two points in the posthatch growth phase (4 and 14 weeks of age). Growth hormone (GH) concentration was determined for each sample by radioimmunoassay using a recombinant chicken growth hormone preparation as standard. Data were evaluated for age- and sex-related differences. Four-week-old male and female turkeys displayed a pulsatile pattern of GH secretion. Growth hormone secretory profile characteristics differed significantly between ages with regard to overall mean, number of peaks, amplitude of peaks, interval between peaks, baseline, and total GH detected. Male four-week-old turkeys had a peak amplitude significantly greater than that of females of the same age. Older (14-week-old) male turkeys demonstrated a significantly greater nunber of GH secretory peaks than females during the 8-hr sampling period; however, overall it did not appear that the older birds had an organized pattern of GH secretion above baseline levels.

Effects of hypothalamic periventricular lesions on pulsatile growth hormone secretion.

The purpose of this study was to determine the effects of destroying somatostatin (SRIF) neurons of the periventricular (PV) nucleus of the hypothalamus on the pulsatile pattern of growth hormone (GH) secretion in female rats. At 6-10 days after placement of PV lesions, blood samples collected every 15 min for 3-4 h showed an elevation in baseline GH levels and an increase in the amplitude of GH secretory peaks; the frequency of pulses was not affected. These changes were associated with an increase in mean integrated plasma GH levels. The alterations appeared transient because nonstress plasma GH levels were normal in two blood samples collected between 6 and 17 weeks after lesion placement and at autopsy at 17 weeks. Stress-induced suppression of GH secretion was also unaffected by the PV lesions. These lesions severely compromised the SRIF system that projects to the median eminence because the median eminence content of SRIF was approximately 85% depleted in the lesioned group. These results confirm that the hypothalamic PV nucleus is essential for maintaining most of the SRIF in the median eminence and demonstrate that damage to the PV nucleus causes transient alterations in the pulsatile pattern of GH secretion. However, the PV nucleus does not appear to play a major role in driving pulsatile GH secretion.