Peak Growth Hormone Secretion Research Articles

Hypothalamic Distribution of Somatostatin mRNA Expressing Neurones Relative to Pubertal and Adult Changes in Pulsatile Growth Hormone Secretion in Mice

The age-associated decline in growth hormone (GH) secretion may be a consequence of the reduction in the number of GH-releasing hormone (GHRH) positive neurones. However, it remains unclear whether an alteration in the number or distribution of somatostatin (SST) neurones contributes to this change. In the present study, we characterised the role of SST in modulating the change in pulsatile GH secretion in male C57Bl/6J mice throughout puberty and into early adulthood. We assessed pulsatile GH secretion in mice at 4, 8 and 16weeks of age. These ages correspond to early pubertal, early adulthood and adulthood, respectively. We show an elevation in peak, total and pulsatile GH secretion coinciding with periods of rapid linear growth. Using in situ hybridisation and morphometric methods, we mapped the distribution of Sst mRNA expression within the mouse brain relative to this change in pulsatile GH secretion. The results obtained show that altered pulsatile GH secretion in male mice from 4-16weeks of age does not coincide with a significant change in the number of Sst mRNA expressing neurones or an abundance of Sst mRNA expression throughout the arcuate nucleus (ARC) and periventricular nucleus (PeV). Rather, we observed a progressive decline in Sst mRNA expressing neurones within subnuclei of the paraventricular nucleus at this time. We conclude that structural changes in Sst expression within the PeV and ARC may not reflect the observed decline in pulsatile GH secretion in mice from puberty into early adulthood.

Chronic cognitive sequelae after traumatic brain injury are not related to growth hormone deficiency in adults

The objective of the study was to asses the possible influence of hypothalamo-pituitary deficiencies, and growth hormone (GH) deficiency in particular, on cognition in adult patients with traumatic brain injury (TBI). TBI is a recently identified risk factor for cognitive deficits and hypopituitarism. Even the patients with favorable outcome after TBI may present with persistent bodily, psychosocial, and cognitive impairments, resembling patients with untreated partial or complete pituitary insufficiency. We performed retrospective and cross-sectional study of endocrine and cognitive function in TBI in 61 patients (aged 37.7 +/- 1.7 years) of both sexes (44 m,17 f), at least 1 year after TBI (3.9 +/- 0.6 years). Serum insulin-like growth factor 1 (IGF-I), thyroxin, thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (in men), prolactin, and cortisol were measured, and GH secretion was assessed by growth hormone releasing hormone (GHRH) + growth hormone releasing peptide-6 (GHRP-6) test. Cognitive function was assessed by using a standard neuropsychological battery. GH deficiency (GHD) and GH insufficiency (GHI) were found in 20 patients (32.8%). After adjustment for confounders [age, body mass index (BMI), education level, time elapsed from TBI], there were no significant differences in results of neuropsychological tests between patients with TBI with GHD, GHI, and normal GH secretion. There were no correlations of neuropsychological variables with stimulated peak GH secretion or IGF-I level. GHD persists long after the TBI, independently of trauma severity and age at traumatic event. GH secretion is more sensitive to TBI than other pituitary hormones. No evidence is found for an association of cognitive function impairment and somatotropic axis impairment in adult patients tested more than 1 year after the TBI.

Inhaled Beclomethasone Dipropionate Acutely Stimulates Dose-Dependent Growth Hormone Secretion in Healthy Subjects

It is well known that systemic administration of corticosteroids has a dual effect on growth hormone (GH) secretion in man: acute systemic administration stimulates GH release, whereas chronic administration consistently blocks it. In this study, we evaluate whether administration of inhaled corticosteroids could acutely stimulate GH secretion, and whether this effect could be dose related. Double-blind, placebo-controlled, crossover study. Eight normal male volunteers all recruited at our institution. Administration of increasing doses of inhaled beclomethasone dipropionate (BDP; range, 50 to 1,500 mug) or placebo. Blood samples for GH determinations were collected at - 15, 0, 60, 120, 180, 240, 300, and 360 min in relation to BDP or placebo administration. The results of this study show a peak GH secretion at 240 min after the administration of BDP at doses > 100 microg. The comparisons among the peaks obtained with increasing doses showed a dose-response effect on GH secretion, starting from 100 to 1,000 microg. BDP 1,500 microg did not induce a peak significantly different from that obtained with 1,000 microg. When we calculated the GH response to BDP as an area under the curve (micrograms per liter x 6 h), the data confirmed that GH secretion was elicited in a dose-related manner. Our data show that inhaled BDP at dose > 100 microg acutely stimulates GH secretion in a strictly dose-dependent manner. We propose this test as a surrogate for systemic absorption and as a valuable test to compare systemic effects among different inhaled steroids.

Effects of hypothalamic equivalent uniform dose on growth hormone secretion

Purpose/Objective: Following a study of radiation dose-volume effects on growth hormone (GH) secretion, we investigated dose effects using equivalent uniform dose (EUD) delivered to the hypothalamus. We correlated the EUD to peak GH secretion after conformal radiotherapy (CRT) in children with localized primary brain tumors.

Growth hormone-releasing factor on growth hormone secretion in prepubertal calves.

The effects of iv administration of growth hormone-releasing factor (GRF) on growth hormone (GH) release and on nitrogen metabolism were measured in prepubertal calves. Crossbred beef heifers (111 kg) were used in a Latin square design to test the effects of 0, 0.01, 0.033, 0.067, and 0.1 microgram human pancreatic (hp) GRF [hpGRF (1,40)OH]/kg body wt on plasma GH concentrations. When they were given doses of 0.067 and 0.1 microgram hpGRF/kg body wt, plasma GH increased (P less than 0.05) within 5-15 min, compared with injections of control buffer, and then returned to preinjection concentrations. The response to 0.067 microgram hpGRF/kg body wt every 3 hr for 42 hr was studied in five heifers (137 kg body wt). The animals responded to 50% of the GRF injections with an increase in plasma GH during every 6-hr period measured. Nitrogen retention, hormone concentrations, and weight gain were measured in five bull calves (90 kg body wt) administered 0 or 0.067 microgram Nle rat hypothalamic GRF (1,29)NH2/kg body wt every 4 hr for 10 days. Metabolic parameters were interpreted to indicate an anabolic response to GRF even though increases of 16% in nitrogen retention, 23% in plasma somatomedin C concentrations, and 36% in weight gain with pulsatile GRF treatment were variable and statistically similar to those of controls. These results indicate that GRF induces peak GH secretion within 15 min in prepubertal calves and that calves can respond to multiple injections of GRF with an increase in plasma GH.

The mechanism of the adolescent growth spurt induced by low dose pulsatile GnRH treatment.

We have used GnRH administered in a pulsatile fashion to treat 26 patients (12M:14F) with delayed puberty. Treatment was for a mean of 1.05 years (range, 0.3-1.6). Mean age at the onset of treatment was 16.4 years in the girls (range, 12.7-28.2) and 15.8 years in the boys (range, 13.8-17.8). At different stages of sexual maturation, overnight serum samples for growth hormone (GH) were taken at 15 min intervals between 2000 h and 0600 h. The girls had a peak growth velocity which occurred between breast stages 2 and stage 3 (B2/3). GH secretion (both sum of the GH peaks and area under the GH pulse) increased at B2 and reached a peak at B3. Growth acceleration in the boys started at the attainment of a 9-10 ml testicular volume and reached a peak at 11-15 ml. The boys demonstrated an initial fall in GH secretion with the onset of treatment until the attainment of 9-10 ml testicular volume; peak GH secretion occurred at the attainment of 11-12 ml testicular volume. There was no change in GH pulse frequency during treatment in either sex. These observations and the maintenance of the normal relationship of the growth spurts to the appearance of secondary sexual characteristics are relevant to the mechanisms and timing of the adolescent growth spurts in normal girls and boys.

Secretory bursts of growth hormone secretion in the dog may be initiated by somatostatin withdrawal.

In 28 6-h experiments on 10 conscious resting trained male dogs, plasma growth hormone (GH) was determined at 5-min intervals by radioimmunoassay. For all experiments, the basal GH concentration in plasma was 0.80 +/- 0.06 ng mL-1. In each experiment, 1-3 secretory bursts of GH occurred, raising plasma GH 2.4 to 15.3 times basal concentrations (for all 43 bursts, 6.6 +/- 0.4 times the basal value). Metabolic clearance rates (MCR) and apparent distribution volumes (V) were determined, using stepwise infusions of canine GH. The MCR (3.99 +/- 0.30 mL kg-1 min-1) and V (57.9 +/- 5.5 mL kg-1) were used to transform the GH concentration versus time data into GH secretion rates, using a single compartment approach. Basal GH secretion rates for all 28 experiments were 3.12 +/- 0.24 ng kg-1 min-1. The secretory bursts yield peak GH secretion rates of 9.4 +/- 0.8 times basal secretion and these steep-sloped bursts last 25.1 +/- 1.2 min. Six-hour infusions of 0.15 microgram kg-1 min-1 of somatostatin (SRIF) abolished all secretory bursts but did not lower basal secretion rates. In five of seven SRIF infusion experiments in which samples were taken after the infusion ceased a secretory burst was seen in the hour following cessation of infusion (in four cases within 10 min). These secretory bursts lasted 23.0 +/- 2.9 min and were similar to those seen in control experiments. Infusions of SRIF at 0.05 microgram kg-1 min-1 had no effect. These results imply that during basal GH secretion, a surfeit of SRIF impinges on the somatotrophs, as extra SRIF does not further lower basal secretion. However, during secretory bursts, very little SRIF must be present, as exogenous SRIF blocks these bursts. The bursts are similar in duration to overshoots provoked in perifused dispersed rat somatotrophs by removal of an SRIF signal. It seems likely that their cause in vivo is similar. (All values are means +/- SEM.)

Growth hormone secretion during sleep.

Plasma growth hormone (GH), insulin, cortisol, and glucose were measured during sleep on 38 nights in eight young adults. Blood was drawn from an indwelling catheter at 30-min intervals; EEG and electrooculogram were recorded throughout the night. In seven subjects, a plasma GH peak (13-72 mmug/ml) lasting 1.5-3.5 hr appeared with the onset of deep sleep. Smaller GH peaks (6-14 mmug/ml) occasionally appeared during subsequent deep sleep phases. Peak GH secretion was delayed if the onset of sleep was delayed. Subjects who were awakened for 2-3 hr and allowed to return to sleep exhibited another peak of GH secretion (14-46 mmug/ml). Peak GH secretion was not correlated with changes in plasma glucose, insulin, and cortisol. The effects of 6-CNS-active drugs on sleep-related GH secretion were investigated. Imipramine (50 mg) completely abolished GH peaks in two of four subjects, whereas chlorpromazine (30 mg), phenobarbital (97 mg), diphenylhydantoin (90 mg), chlordiazepoxide (20 mg), and isocarboxazid (30 mg) did not inhibit GH peaks. Altered hypothalamic activity associated with initiation of sleep results in a major peak of growth hormone secretion unrelated to hypoglycemia or changes in cortisol and insulin secretion.