Peak Growth Hormone Concentrations Research Articles

Gender is more influential than hormonal status in regulating peak growth hormone (GH) response to triple secretagogues

OBJECTIVE: GH responses to secretagogues demonstrate significant variability due to factors such as gender, hormonal status, and body mass index (BMI). Our objective is to look at the gender-specific response to maximal GH stimulation and determine if three pathway-specific GH secretagogues will promote maximal GH secretion regardless of BMI or sex-steroid milieu. As such, this information would be useful in developing a widely applicable test for assessing GH reserve.DESIGN: IRB approved randomized controlled trial.MATERIALS AND METHODS: The cohort comprised 36 healthy adults who ranged in age from 46-74 years with a BMI 20.3-31.5 kg/m2. There were 21 women who were randomized to receive either estradiol replacement via patch or placebo. The 15 men were randomized to receive testosterone by IM injection or placebo. All subjects then received L-arginine to limit somatostatin inhibition of GH releasing hormone (GHRH) as well as GHRH and ghrelin as a triple-secretagogue combination. GH was sampled every 10 minutes and GH concentrations were compared using a one-way ANOVA. The association between log(peak GH) and BMI was assessed using linear regression.RESULTS: Mean triply stimulated GH concentrations were 2.2-fold higher in women than men regardless of sex steroid supplementation (p=0.001). Peak triply stimulated GH concentrations were >2 times higher in women compared to men irrespective of hormonal milieu (p<0.001). Nadir GH concentrations were maximal in women receiving estradiol replacement (p<0.001). BMI was not found to be correlated with peak GH concentration (r2= 0.068, p= 0.12).CONCLUSION: Gender appears to be a primary driver for GH responsivity regardless of hormonal milieu. BMI was not found to be an influential covariate. To this end, these data do not substantiate the hypothesis that a triple secretagogue combination functions independently of gender. Gender differences, more so than hormonal milieu and BMI are important factors in developing a test for GH reserve. OBJECTIVE: GH responses to secretagogues demonstrate significant variability due to factors such as gender, hormonal status, and body mass index (BMI). Our objective is to look at the gender-specific response to maximal GH stimulation and determine if three pathway-specific GH secretagogues will promote maximal GH secretion regardless of BMI or sex-steroid milieu. As such, this information would be useful in developing a widely applicable test for assessing GH reserve. DESIGN: IRB approved randomized controlled trial. MATERIALS AND METHODS: The cohort comprised 36 healthy adults who ranged in age from 46-74 years with a BMI 20.3-31.5 kg/m2. There were 21 women who were randomized to receive either estradiol replacement via patch or placebo. The 15 men were randomized to receive testosterone by IM injection or placebo. All subjects then received L-arginine to limit somatostatin inhibition of GH releasing hormone (GHRH) as well as GHRH and ghrelin as a triple-secretagogue combination. GH was sampled every 10 minutes and GH concentrations were compared using a one-way ANOVA. The association between log(peak GH) and BMI was assessed using linear regression. RESULTS: Mean triply stimulated GH concentrations were 2.2-fold higher in women than men regardless of sex steroid supplementation (p=0.001). Peak triply stimulated GH concentrations were >2 times higher in women compared to men irrespective of hormonal milieu (p<0.001). Nadir GH concentrations were maximal in women receiving estradiol replacement (p<0.001). BMI was not found to be correlated with peak GH concentration (r2= 0.068, p= 0.12). CONCLUSION: Gender appears to be a primary driver for GH responsivity regardless of hormonal milieu. BMI was not found to be an influential covariate. To this end, these data do not substantiate the hypothesis that a triple secretagogue combination functions independently of gender. Gender differences, more so than hormonal milieu and BMI are important factors in developing a test for GH reserve.

Gonadal Status and Body Mass Index Jointly Determine Growth Hormone (GH)-Releasing Hormone/GH-Releasing Peptide Synergy in Healthy Men

Sex steroid hormones potentiate whereas increased body mass index (BMI) represses GH secretion. Whether sex steroids modify the negative effect of BMI on secretagogue-induced GH secretion in men is not known. The issue is important in designing GH-stimulation regimens that are relatively insensitive to both gonadal status and adiposity. Our objective was to compare the relationships between BMI and peptide-stimulated GH secretion in men with normal and reduced testosterone and estradiol availability. The study was performed at an academic medical center. Healthy young men were included in the study. Randomized separate-day iv infusion of saline and/or maximally effective doses of L-arginine/GHRH, L-arginine/GH-releasing peptide (GHRP)-2, and GHRH/GHRP-2 in eugonadal (n=12) and experimentally hypogonadal (n=10) men was performed. Regression of paired secretagogue-induced GH responses on BMI was determined. In eugonadal men, peak GH concentrations correlated negatively with BMI. In particular, BMI accounted for only 38% of the response variability after L-arginine/GHRH (P=0.0165), but 62% after GHRH/GHRP-2 (P=0.0012) and 65% after L-arginine/GHRP-2 (P=0.00075). In contrast, in hypogonadal men, GH responses were uncorrelated with BMI. The negative effects of BMI on peak GH responses in eugonadal and hypogonadal states differed most markedly after stimulation with GHRH/GHRP-2 (P=0.0019). This contrast was corroborated using integrated GH responses (P=0.0007). Short-term experimental gonadal sex hormone depletion attenuates dual secretagogue-stimulated GH secretion in lean young men. The inhibitory effect of relative adiposity on GH secretion appears to predominate over that of acute sex steroid withdrawal.

Diagnostic strategy for growth hormone deficiency: relevance of IGF-1 determination as a screening test

Background Adult growth hormone (GH) deficiency must be diagnosed before prescribing therapeutic recombinant human GH. We studied the clinical relevance of a diagnostic strategy for growth hormone deficiency (GHD) using IGF-1 determination as a first step. Methods In 2000 and 2001, we tested 142 adult patients with hypothalamo-pituitary disorders for somatotropic function using Insulin Tolerance Test (ITT), the reference test for the diagnosis of GHD, with concomitant Insulin-like growth factor–1 (IGF-1) determination, a marker of somatotropic function. Patients were classified as GHD (peak GH concentration < 3 ng/ml with the ITT) or normal. Setting Monocenter prospective study in a tertiary referral center. Results GHD was diagnosed in 61 subjects. Using a ROC curve, a threshold IGF–1 concentration of 175 ng/ml yielded a negative predictive value of 89 ± 5%. A diagnostic strategy with IGF-1 determination as the first step followed by ITT for patients with an IGF-1 concentration below 175 ng/ml missed five of the 61 GHD patients, avoided 46/142 ITT and reduced the cost of diagnosis by 15%. Conclusion We propose the use of a strategy consisting of IGF-1 determination followed, if below 175 ng/ml by confirmatory ITT to diagnose GHD in adults.

The effect of exercise type on immunofunctional and traditional growth hormone

The purpose of this study was to compare the growth hormone (GH) response, including the immunfunctional (IF) GH response, between an acute bout of aerobic and resistance exercise in the same subjects. Ten cross-trained males (24.3 +/- 1.2 years) performed both 30 min of continuous cycling at 70% of VO(2max), and intermittent free weight squatting at 70% of 1-RM, in a randomly assigned crossover design, separated by at least 1 week. Blood samples were collected at 10-min intervals for 2 h (30 min rest, 30 min exercise, 60 min recovery) and analyzed for total human and IF GH. After adjusting for the amount of work performed per minute of exercise, integrated GH AUC was significantly greater during the resistance session than the aerobic session as measured by both the total and IF GH assays (P = 0.008 and P = 0.014, respectively). Peak GH concentrations were significantly greater during the resistance session than the aerobic session (P = 0.05). A similar overall GH pattern was observed in response to both types of exercise, with peak values occurring at the end of exercise, regardless of the GH assay used. These data demonstrate that in young, cross-trained males, intermittent resistance exercise elicits a greater response of GH, including IF GH, compared to a continuous aerobic session, when controlling for the work performed per minute, intersubject variability, relative exercise intensity and session duration.

Influence of acute alcohol ingestion on the hormonal responses to modest hypoglycaemia in patients with Type 1 diabetes

To determine whether mild alcohol intoxication (45-50 mg/dl) influences counterregulatory hormone responses to moderate hypoglycaemia (2.8 mmol/l)in patients with Type 1 diabetes. Seventeen subjects (14 male, age range 21-46 years) with Type 1 diabetes underwent four hyperinsulinaemic glucose clamps: euglycaemia with placebo; euglycaemia with alcohol (0.4 g/kg); hypoglycaemia (2.8 mmol/l for 65 min)with placebo; and hypoglycaemia (2.8 mmol/l for 65 min) with alcohol (0.4 g/kg). Arterialized venous blood samples were taken for measurement of insulin and counterregulatory hormones. During hypoglycaemia, peak growth hormone concentrations were significantly lower after alcohol compared with placebo (14.3 +/- 2.9 vs.25.9 +/- 3.4 microg/l,P< 0.001) associated with reduced insulin sensitivity in both hypoglycaemia and euglycaemia studies. We found an attenuated growth hormone response to hypoglycaemia associated with mild alcohol intoxication. Although this may potentially contribute to impaired recovery of glucose after hypoglycaemia in patients with Type 1 diabetes, it appears to be offset by a reduction in insulin action.

Apomorphine‐Induced Growth Hormone Response Is Attenuated by Ethanol but Not Dextromethorphan

Misuse of alcohol drinking is a major health problem. Alcohol decreases spontaneous growth hormone (GH) secretion, but the mechanism is unclear. The aim of this study was to test whether administration of alcohol (study 1) or a N-methyl d-aspartate (NMDA) receptor antagonist (study 2) attenuates the GH response to pharmacological dopaminergic stimulation. The 2-session repeated measures design was conducted at the endocrine laboratory at the Department of Psychiatry at the Free University Berlin. Twenty healthy Caucasian males aged 35+/-10 years without a history of alcohol use disorders were tested using the Apomorphine (APO) challenge test. In study 1, we injected APO (0.01 mg/kg s.c.) 1 hour after oral administration of 1 g/kg ethanol and placebo, respectively. In study 2, the APO challenge was conducted after 0.3 mg/kg dextromethorphan (DXM) and placebo. The main outcome measures were the peak serum GH concentration and area under the time/concentration curve up to 120 minutes after APO. The effects of ethanol and DXM were tested using the Wilcoxon signed-rank tests. Compared with placebo, alcohol significantly decreased the APO-induced GH release (mean and SEM peak GH concentration 19.9+/-3.2 vs 6.2+/-1.9 ng/mL, p=0.002). Dextromethorphan did not change APO-induced GH response (22.5+/-5.4 vs 21.0+/-5.8 ng/mL, p=0.105). A single intermediate alcohol dose markedly reduces GH response to dopaminergic stimulation. Although alcohol is thought to stimulate dopaminergic function in certain pathways, but not necessarily in the hypothalamus, our results are in line with the alcohol effect on baseline GH secretion. Growth hormone suppression appears not to be mediated by ethanol's NMDA-antagonistic properties.

Growth hormone and muscle function responses to skeletal muscle ischemia

We examined the effects of ischemia (ISC) alone and with low-intensity exercise (ISC+EX) on growth hormone (GH) and muscle function responses. Nine men (22 +/- 0.7 yr) completed 3 study days: an ISC day (thigh cuff inflated five times, 5 min on, 3 min off), an ISC+EX day [knee extension at 20% maximal voluntary contraction (MVC) with ISC], and a control day. MVCs and submaximal contraction tasks (15 and 30% MVC) were performed before and following the perturbations. Surface electromyogram signals were collected from thigh muscles and analyzed for median frequency and root mean square alterations. Blood samples were collected every 10 min (190 min total) and analyzed for GH concentrations. Peak GH concentrations and GH area under the curve were highest (P < 0.01) on the ISC+EX day (7.5 microg/l and 432 microg.l(-1).min(-1), respectively) compared with the ISC (0.9 microg/l and 76.4 microg.l(-1).min(-1)), and CON (1.1 microg/l and 83.8 microg.l(-1).min(-1)) days. A greater GH pulse amplitude, mass/pulse, and production rate were also observed on the ISC+EX day (P < 0.05). Following the intervention, force production decreased on the ISC and ISC+EX days by 16.1 and 55.8%, respectively, and did not return to baseline values within 5 min of recovery. During the submaximal contractions, median frequency shifted to lower frequencies for most of the muscles examined, and root mean square electromyogram was consistently elevated for ISC+EX day. In conclusion, ISC coupled with resistance exercise acutely increases GH levels and reduces MVC, whereas ISC alone decreases force capacity, without alterations in GH levels.

Reciprocal changes in endogenous ghrelin and growth hormone during fasting in healthy women

Ghrelin stimulates growth hormone (GH) secretion, but it is unknown whether there is a feedback of GH on ghrelin secretion. In this study, we characterized the relatedness of GH and ghrelin in a model of acute caloric deprivation in 10 healthy women (age 26.7 +/- 1.6 yr) during a 4-day fast in the early follicular phase. GH, ghrelin, and cortisol were assessed every hour over 24 h during an isocaloric diet and after a 4-day complete fast. Sampling during a normal diet at baseline demonstrated that ghrelin decreased 17.9% within 1 h after meals (P < 0.0001), but there was no meal effect on GH. BMI (22.3 +/- 0.4 vs. 21.5 +/- 0.4 kg/m2, P < 0.0001) and IGF-I (312 +/- 28 vs.124 +/- 22 ng/ml, P < 0.0001) decreased during fasting. Mean 24-h GH increased (2.6 +/- 0.5 vs. 5.6 +/- 0.5 ng/ml, P < 0.001), but ghrelin decreased (441.3 +/- 59.7 vs. 359.8 +/- 54.2 pg/ml, P = 0.012). The peak ghrelin level decreased from 483.5 to 375.6 pg/ml (P < 0.0001), and the time of the peak ghrelin changed from 0415 to 1715. In contrast, the diurnal pattern of GH was maintained, with increases in the nadir (1.1 to 3.4 ng/ml) and peak GH concentrations (4.1 to 7.9 ng/ml) from the fed to fasted state (P < 0.0001). The change in morning GH concentrations was inversely related to the change in ghrelin (r = -0.79, P = 0.012). During complete short-term caloric deprivation in healthy women, ghrelin decreases, even as GH rises, and these processes appear to be reciprocal, suggesting that GH exhibits feedback inhibition on ghrelin. Our data provide new evidence of the physiological relationship of GH and ghrelin in response to changes in protein-energy metabolism.

Prior Endurance Exercise Attenuates Growth Hormone Response to Subsequent Resistance Exercise

Free fatty acids (FFA) affects anterior pituitary function and an acute increase in circulating FFA attenuates the growth hormone (GH) secretion stimulated pharmacologically (Casanueva et al. 1987). Prolonged endurance exercise augments lipolysis, and subsequently causes increases in circulating FFA and glycerol. Although resistance exercise is a potent stimulus for GH secretion, the GH response after a single bout of resistance exercise might be diminished by prior endurance exercise and a concomitant increase in FFA. PURPOSE The present study investigated the influence of prior endurance exercise on both anabolic and catabolic hormone responses to subsequent resistance exercise. METHODS Ten males exercised on a cycle ergometer at 50% of maximal oxygen uptake for 60 min and subsequently completed a resistance exercise (bench press and leg press, 4 sets at 10 repetition maximum with an interset rest period of 90 s; ER trial). Alternatively, the subjects performed the protocol with prior endurance exercise limited to 5 min on a separate day (R trial). Blood was obtained before and after the endurance exercise, and 10-, 20- and 30-min after the resistance exercise. Maximal isometric torque was measured on three times to evaluate fatigue: before and after endurance and resistance exercises. RESULTS No significant difference was seen in both resting and post-exercise concentrations between ER and R trials for glucose, lactate, total testosterone and cortisol. In the ER trial with prior endurance exercise of 60 min, FFA concentration increased after endurance exercise (0.34±0.06 to 1.13±0.16 mEq/L, P < 0.01), whereas that in the R trial did not (0.38±0.07 to 0.34±0.07 mEq/L, NS). GH concentration slightly increased after endurance exercise in the ER trial, whereas that in the R trial did not. After resistance exercise, it increased compared to that of its preexercise value in the R trial (P < 0.01), whereas in the ER trial, it decreased. The peak concentration of GH after resistance exercise was significantly greater in the R trial (10.0±2.1 ng/mL) than in the ER trial (3.6±1.8 ng/mL; P < 0.05). CONCLUSIONS These results indicate that the GH response to resistance exercise is attenuated by prior endurance exercise. This effect might be caused by the increase in blood FFA concentration during the resistance exercise. Supported by Grant from the Ministry of Education, Science, Sports and Culture of Japan.

Is growth hormone stimulation testing in children still appropriate?

The diagnosis of growth hormone deficiency (GHD) historically has relied on measurement of growth hormone (GH) concentrations following stimulation, usually with a non-physiologic provocative agent. Despite the use of more specific GH assays, the peak concentration of GH below which a child is considered GH deficient has risen. We examine the pitfalls associated with GH stimulation tests, specifically, the lack of reliability and accuracy of these tests, and their inability to predict who will benefit from GH therapy. We recommend that GH stimulation tests no longer routinely be used for the diagnosis of GHD in children.

Effects of Selection for Milk Yield on Growth Hormone Response to Growth Hormone Releasing Factor in Growing Holstein Calves

Bull and heifer calves (n=81) from genetic lines of Holstein cows that differed by more than 4000kg milk/305-d lactation were used to determine effects of selection for milk yield on growth hormone (GH) response to a GH releasing factor (GRF) analog. Calves received GRF (4μg/100kg BW) on 10, 56, 140, 196, 252, and 364±3 d of age. Jugular blood samples (n=15) were obtained from −30 to 120min relative to GRF administration. Area under the GH response curve (0 to 60min, AUC60) was quantified after subtracting mean prechallenge GH concentrations. Data were analyzed for effects of line, age, gender, and their interactions with PROC MIXED of SAS for repeated measures and incorporated the spatial power law for unequally spaced data with age as the repeated effect. Means were considered different when P<0.05. Prechallenge GH concentrations did not differ between lines, were greater in bulls than heifers (4.6 vs. 3.7ng/ml), and decreased with age. The AUC60 decreased with age but did not differ between lines. Heifers responded more to GRF than bulls (1550 vs. 1336ng×min/ml). Peak GH concentration decreased with age and was less in bulls than heifers (54.7 vs. 62.1ng/ml) but did not differ between lines. Although plasma GH has been identified as an inheritable trait, we conclude the GH variables measured in this study were not useful in predicting genetic merit of calves from these substantially different lines of cows.

Pituitary adenylate cyclase-activating polypeptide induces secretion of growth hormone in cattle

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a hypothalamic neuropeptide that stimulates release of growth hormone (GH) from cultured bovine anterior pituitary gland cells, but the role of PACAP on the regulation of in vivo secretion of GH in cattle is not known. To test the hypothesis that PACAP induces secretion of GH in cattle, meal-fed Holstein steers were injected with incremental doses of PACAP (0, 0.1, 0.3, 1, 3, and 10 μg/kg BW) before feeding and concentrations of GH in serum were quantified. Compared with saline, injection of 3 and 10 μg PACAP/kg BW increased peak concentrations of GH in serum from 11.2 ng/ml to 23.7 and 21.8 ng/ml, respectively ( P < 0.01). Peak concentrations of GH in serum were similar in steers injected with 3 or 10 μg PACAP/kg BW. Meal-fed Holstein steers were then injected with 3 μg/PACAP/kg BW either 1 hr before feeding or 1 hr after feeding to determine if PACAP-induced secretion of GH was suppressed after feeding. Feeding suppressed basal concentrations of GH in serum. Injection of PACAP before feeding induced greater peak concentrations of GH in serum (19.2 ± 2.6 vs. 11.7 ± 2.6 ng/ml) and area under the response curve (391 ± 47 vs. 255 ± 52 ng · ml −1 min) than injection of PACAP after feeding, suggesting somatotropes become refractory to PACAP after feeding similar to that observed by us and others with growth hormone-releasing hormone (GHRH). We concluded that PACAP induces secretion of GH and could play a role in regulating endogenous secretion of GH in cattle, perhaps in concert with GHRH.

LOW INTENSITY RESISTANCE EXERCISE FOLLOWING HIGH INTENSITY RESISTANCE EXERCISE STIMULATES GROWTH HORMONE SECRETION IN MEN

To examine endogenous growth hormone response to various heavy resistance exercise protocols, eight active male subjects performed five resistance exercise protocols randomly on separate days. The protocols were categorized into three types of exercise with different objectives. The first type was resistance exercise which consisted of five sets at 90% of one repetition maximum (IRM) with 3-min rest periods between sets (Strength type: S). The second type was resistance exercise which consisted of nine sets at 40–80% of 1RM with 30 sec or 3-min rest periods between sets (Hypertrophy type: H). The third type included 3 separated protocols, each of which consisted of a combination of S and H (Combination type). The combination type was characterized by an additional relatively low intensity set following a series of high intensity sets (five sets at 90% of 1RM). The load used in the additional set was either 90% of 1RM (C90), 70% of 1RM (C70) or 50% of 1RM (C50). The exercise performed in all sets of all protocols was bilateral knee extension repeated until exhaustion. Serum growth hormone concentration (GH) and whole blood lactate concentration were determined preexercise and at 0–60 min postexercise. Relative changes in thigh girth (%GIRTH) and knee extension maximal isometric force were determined preexercise and immediately postexercise. Minor but significant changes in peak growth hormone concentration (GHpeak) were observed in S and C90. GHpeak in H was the highest value of all protocols. On the other hand, GHpeak in C50 showed a significantly (P < 0.05) higher increase than in S and a relatively higher increase than in C70. In addition, peak lactate concentration and %GIRTH correlated significantly (P < 0.05) with GHpeak. These findings suggest that an additional low intensity set (50% of 1RM) following a series of high intensity sets significantly increases GH secretion. It is possible that factors related to greater metabolite changes in working muscle resulted in the greater GH response.

Effects of the administration of growth hormone-releasing peptide-2 (GHRP-2) orally by gavage and in feed on growth hormone release in swine

The experiments were conducted to determine the effects of the administration of growth hormone-releasing peptide-2 (GHRP-2, also named KP102), both orally by gavage and in feed, on the release of growth hormone (GH) in swine and to investigate whether attenuation of the GH response occurs after short-term treatment with the peptide in feed. In the first experiment, saline or GHRP-2 at doses of 1, 4.5 and 9 mg/kg body weight (BW) was dissolved in 15 ml saline and administered orally as a bolus by gavage to cross-bred castrated male swine ( n = 6). Orally administered GHRP-2 stimulated dose-related increases in peak concentrations of GH, with a return to basal by 120 min. After administering GHRP-2 orally, peak concentrations of GH and areas under the GH response curves (GH AUCs) for 180 min were higher (P < 0.05) than those in saline controls. In Experiment 2, GHRP-2 at doses of 0 (served as control), 1, 4.5 and 9 mg/kg BW was mixed in 150 g of feed and offered to cross-bred castrated male swine ( n = 6) at 0900 hr and 1700 hr daily for a 3-d period. Administration of 1 mg/kg BW GHRP-2 to swine in feed failed to stimulate the release of GH, but GHRP-2 at doses of 4.5 and 9 mg/kg BW significantly (P < 0.05) increased plasma concentrations of GH after initial and final treatments at 0900 hr on Days 1 and 3 of treatment, respectively. Peak concentrations of GH and GH AUCs for 180 min after the initial and final treatments in the 4.5 and 9 mg/kg BW GHRP-2-treated swine were higher (P < 0.05) than those in controls. After 3 d of treatment with GHRP-2 in feed at doses of 4.5 and 9 mg/kg BW, GH responses to the peptide were maintained. The results of the present study indicate that the administration of GHRP-2 orally by gavage and in feed stimulates the release of GH in swine, and that the GH-releasing effect of the peptide does not become desensitized after short-term administration in feed.

Growth Hormone-Releasing Peptide-2 (GHRP-2) Acts Synergistically with Growth Hormone-Releasing Hormone (GHRH) to Release Growth Hormone (GH) in Swine

The aim of the present study was to examine the growth hormone (GH) response to the combined and repeated administrations of growth hormone-releasing peptide-2 (GHRP-2) plus growth hormone releasing hormone (GHRH) in swine. Six cross-bred castrated male swine, 130-135 days of age were used in this study. Animals were given a single intravenous (i.v.) injection of either GHRP-2 (30μg/kg BW), GHRH (1μg/kg BW) and GHRP-2 (30μg/kg BW) plus GHRH (1μg/kg BW) or 5ml saline (served as control) in random order with two days apart. GHRP-2 or GHRH alone and in combination with together stimulated the release of GH in swine. The peak concentrations of GH and areas under the GH response curve (GH AUC) for 120min after these treatments were significantly higher (P<0.01) than those in controls. The combined administration of these two peptides [GHRP-2 (30μg/kg BW) and GHRH (1μg/kg BW)] resulted in a GH AUC significantly greater than the arithmetic sum of those following their separate administrations (P<0.05), demonstrating the synergistic effect for GH release. GH responses to two successive i.v. injections of GHRP-2 (30μg/kg BW) plus GHRH (1μg/kg BW) at 2h interval in swine were increased after each injection; however, peak concentration of GH and GH AUC for 120min after the second injection were significantly lower (P<0.01) than those after the first injection. These results of the present study indicated that the combined administration of GHRP-2 and GHRH synergistically stimulates the release of GH in swine, and the GH responses to the co-administration of these two peptides decrease after the repeated injection. These findings suggest that GHRP-2 and GHRH act through different receptors and intracellular signal transduction and can be used together for stimulating further release of GH in swine.

Reproducibility of the insulin tolerance test (ITT) for assessment of growth hormone and cortisol secretion in normal and hypopituitary adult men.

The within subject variability of the insulin tolerance test (ITT) for assessment of growth hormone (GH) status and cortisol reserve has rarely been examined, particularly in patients with hypopituitarism. This becomes important when biochemical criteria are used to determine which adults with hypopituitarism should receive GH and/or cortisol replacement. In the present study we assessed the reproducibility of GH and cortisol responses in repeated ITTs. Baseline insulin-like growth factor 1 (IGF-1) levels were also assessed for reproducibility on each occasion. Three consecutive ITTs were performed in seven normal adult men (ages 22-27 years) and two ITTs in 11 men with hypopituitarism and suspected GH deficiency (ages 23-48 years). Serum GH and IGF-1 were measured by immunoradiometric and cortisol by immunofluorimetric assays. In normal men group peak GH responses did not differ between the three tests. There was no correlation between individual peak values. The within subject peak GH variability was between 4.6 and 59.3%, and the overall variability in 21 tests was 35%. The lowest peak GH concentration was 70 mU/l (27 microg/l). All hypopituitary men had severe GH deficiency (all peak GH concentrations < 4 mU/l (1.5 microg/l) in both tests). There was a highly significant correlation between individual peak GH values (r = 0.95, P < 0.0001). Basal IGF-1-values in normal and hypopituitary men were highly correlated between tests (r = 0.98, P < 0.0001). The overall within subject variability of IGF-1-values was 11.9% in normal and 22.7% in hypopituitary men. In normal men group peak cortisol responses were not different between the three tests. There was a good correlation between individual peak cortisol responses in the three ITTs. The within subject peak cortisol variability (median 8.3%; range 0.7-21.5%) was significantly less than that of GH (P < 0.03) in two of three test comparisons. In hypopituitary men the within subject peak cortisol variability (median 41.6%; range 3.5-92.7%) was significantly greater (P < 0.001) than in normal men. All patients were correctly classified as cortisol deficient or normal in both ITTs. The cortisol response to repeated hypoglycaemia is very reproducible in normal men but the GH response is less so. In hypopituitary men the reproducibility of the GH response is good while that of the cortisol response is poor. However, a single ITT did not misclassify hypopituitary patients who are severely GH and/or ACTH deficient and was therefore adequate for clinical decisions regarding GH and/or cortisol replacement. Nevertheless, it remains possible that a single ITT could misclassify some hypopituitary patients with partial GH or ACTH deficiency.

Which children should receive growth hormone treatment

Growth hormone (GH) has been in clinical use for four decades and there has been much rediscovery of wheels in the past 30 years.1 Childhood growth is GH dependent. Velocity...

The effects of growth hormone-releasing peptide-2 (GHRP-2) on the release of growth hormone and growth performance in swine

The effects of GHRP-2 (also named KP102), a new growth hormone-releasing peptide, on the release of growth hormone (GH) and growth performance were examined in swine. The single intravenous (i.v.) injection of GHRP-2 at doses of 2, 10, 30 and 100 μg/kg body weight (BW) to cross-bred castrated male swine stimulated GH release in a dose-dependent manner, with a return to the baseline by 120 min. The peak GH concentrations and GH areas under the response curves (GH AUCs) for 180 min after the injections of GHRP-2 were higher (P < 0.05) than those after the injection of saline. The GH responses to repeated i.v. injections of GHRP-2 (30 μg/kg BW) at 2-h intervals for 6 h were decreased after each injection. The chronic subcutaneous (s.c.) administration of GHRP-2 (30 μg/kg BW) once daily for 30 days consistently stimulated GH release. The GH AUCs for 300 min after the injections on d 1, 10 and 30 of treatment in GHRP-2-treated swine were higher than those in saline-treated swine. However, chronic administration of GHRP-2 caused a partial attenuation of GH response between d 1 and 10 of treatment. The chronic s.c. administration of GHRP-2 also increased average daily gain for the entire treatment period by 22.35% (P < 0.05) and feed efficiency (feed/gain) by 20.64% (P < 0.01) over the saline control values, but did not significantly affect daily feed intake. These results indicate that GHRP-2 stimulates GH release and enhancing growth performance in swine.

Peak and trough growth hormone (GH) concentrations influence growth and serum insulin like growth factor-1 (IGF-1) concentrations in short children.

Growth hormone (GH) is secreted in a pulsatile fashion promoting growth and a number of diverse metabolic actions. The precise components of the pulsatile signal involved in growth regulation are unclear. A retrospective analysis of 24 h serum GH concentration profiles to evaluate the relative contribution of peak and trough serum GH concentrations to growth regulation, GH response to insulin induced hypoglycaemia (ITT) and serum insulin like growth factor-1 (IGF-1) concentration. Fifty short prepubertal children (age 5.2-11.9 years). Analysis of the hormone profile by a concentration distribution method that determines the concentration at or below which the serum GH concentrations in the 24 hour profile spend a percentage of the total time. The method generates an estimate of the observed concentrations (OC) below which 95% and 5% of the values in the time series lie: OC 95 (peaks) and OC5 (troughs). Twenty six of the children were growing at a normal rate for short children with a height velocity standard deviation score (HVSDS) between +0.4 and -0.8 whereas twenty four were growing more slowly (HVSDS between -0.9 to -3.9). The former group had a mean peak GH response to ITT of 27.3 (11.1) mU/l whereas the latter had a mean value of 8.7 (6.5) mU/l. There was no relationship between (peak and trough GH concentration) and the age of the individual or body mass index. Peak GH levels were positively related to HVSDS and serum IGF-1 values (r = 0.44; P = 0.002 and r = 0.53; P = 0.002, respectively). GH trough levels were inversely related to these measurements (r = -0.29; P = 0.05; and r = -0.46; P = 0.002, respectively). Further analysis showed that individuals with the slowest growth rates and lowest IGF-1 concentrations had the lowest peak and highest trough GH concentrations (ANOVA F = 6.0; P = 0.002). Similarly, the peak GH response to ITT was lowest in those individuals with high troughs and low peaks (ANOVA F = 9.99; P < 0.001). These results suggest that the peak values of a GH concentration profile influence growth rate and the IGF-1 axis whereas elevated trough values have the greatest influence on growth rate and IGF-1 values when GH peaks are low.

Serum Insulin-Like Growth Factor-I, IGF Binding Protein-3 and IGFBP-3 Protease Activity after Cranial Irradiation

The relationship between peak growth hormone (GH), insulin-like growth factor I (IGF-I), IGF-I binding protein 3 (IGFBP-3) and IGFBP-3 protease activity was studied in 28 children and adolescents undergoing investigation of pituitary function 0.4–14.2 years after cranial or craniospinal irradiation for the treatment of CNS tumours distant from the hypothalamic-pituitary axis (n = 16) or prophylaxis against CNS leukaemia (n = 12). Seven out of 15 patients with GH deficiency (GHD) (defined as a peak GH concentration <7.5 ng/ml in a stimulation test) had IGF-I <–2 standard deviation score (SDS). None of the 28 patients had serum IGFBP-3 concentrations measured by radioimmunoassay (RIA) <–1.5 SDS with no difference between those with and without GHD. IGFBP-3 concentrations measured by RIA were strongly correlated to IGFBP-3 band density on Western ligand blot (WLB) (r = 0.71; p < 0.0001). IGFBP-3 protease activity was negatively correlated to IGFBP-3 by RIA (r = –0.55; p < 0.01) and to IGFBP-3 by WLB (r = –0.51; p < 0.01). Twenty-two patients had normal IGFBP-3 protease activity (<30% of the activity in pregnancy serum) indicating that serum IGFBP-3 protease activity does not account for the normal levels of IGFBP-3 in RIA.Low serum IGF-I but normal IGFBP-3 concentrations and in the majority normal IGFBP-3 protease activity was found in patients in the years after CNS irradiation. Neither serum IGF-I nor IGFBP-3 can be used as a reliable index of the development of radiation-induced GHD.