Plasma Growth Hormone Response Research Articles

Roasted Soybeans and an Estrogenic Growth Promoter Affect Growth Hormone Status and Performance of Beef Steers

This study investigated the effects of a roasted soybean (RSB)-supplemented diet and an estrogen implant (SYN; Synovex-S® ear implant, 20 mg estradiol benzoate plus 200 mg progesterone) in young crossbred beef steers on their performance and plasma growth hormone (GH) response to challenge injections of thyrotropin-releasing hormone (TRH) + GH-releasing hormone (GHRH). Twenty individually fed steers (body weight 255 ± 5 kg) were assigned to the following treatments: 1) no SYN and fed a soybean meal-supplemented diet, 2) no SYN and fed the RSB-supplemented diet, 3) plus SYN and soybean meal, and 4) plus SYN and RSB. Steers were fed 1.13 MJ metabolizable energy/kg metabolic body weight daily of an 18% protein diet. After a 5-wk growth period, all steers were challenged (intravenous injection) over a 3-wk period with three levels of a combination of TRH + GHRH (0.1 + 0.01, 1.0 + 0.1, 2.5 + 0.25 µg/kg body weight, respectively). After an additional 3 wk, steers were reimplanted and a second 5-wk growth period was followed by a single challenge of the 1.0 + 0.1 TRH + GHRH dose level. Plasma nonesterified fatty acid concentration was greater when steers were fed the RSB compared with soybean meal (265 vs. 205 µmol/L; P < 0.01; SEM = 9.5). Body weight gains for treatments 1, 2, 3 and 4 were 1.35, 1.21, 1.47 and 1.38 kg/d, respectively (RSB, P < 0.10; SYN, P < 0.07; SEM = 0.06). Gain/dry matter intake (g/kg) means were 184, 167, 197 and 184 (RSB, P < 0.04; SYN, P < 0.07; SEM = 7.5). Feeding roasted soybeans resulted in depressed area under the GH response curve [907, 555, 827 and 989 µg/(L*min) (SYN × RSB, P < 0.03; SEM = 117)] and depressed peak response (37.2, 26.6, 33.5 and 41.1 µg/L [SYN × RSB, P < 0.05; SEM = 4.5]), an effect alleviated by estrogen for young growing steers (Period 1) but not for heavier steers (Period 2).

LIMITED INTRAVENOUS ACCESS: ROLE OF IM VASOPRESSIN IN VASODILATORY SHOCK

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Introduction:Vasopressin is an antidiuretic hormone analog that has become an important drug in the treatment of vasodilatory shock through its vasoconstrictive and water retention properties to maintain blood pressure. We present two cases of vasodilatory shock where intravenous access was limited and intramuscular (IM) vasopressin was used for management. CASE PRESENTATION: Patient 1: An 85 year old female with a medical history of hypertension and colon cancer presented with septic shock. She received dopamine via midline on the upper left arm to maintain blood pressure, with the patient's healthcare proxy refusing a central line. Multiple attempts to obtain venous access for a blood transfusion were unsuccessful. The dopamine drip could not be held due to severe hypotension. The decision was made to administer IM vasopressin (10 Units) to maintain blood pressure while stopping dopamine during the blood transfusion. The transfusion was completed over two hours and the blood pressure improved from 76/39 - 123/63. Patient 2: A 63 year old male with a medical history of smoking and peripheral vascular disease was admitted for tachycardia and hypoxia. He had necrotizing pneumonia and was in septic shock. He continued to be volume unresponsive despite intravenous fluid resuscitation. He was placed on a dopamine drip to maintain blood pressure and became tachycardic and remained in shock. Bedside ultrasound showed signs of volume overload. Twenty units of intramuscular vasopressin was given and blood pressure improved within 15 minutes and was maintained between 120/76-105/69 for 1.5 hours. DISCUSSION: Very frequently we encounter difficulties obtaining intravenous access while resuscitating a patient. Such situations pose an immense challenge in managing shock. Vasopressin is unique in its ability to be utilized intramuscularly.[1] Utilizing medications intramuscularly for urgent situations has a significant impact on management when there is limited, or lack of, intravenous access for hemodynamically unstable patients. The onset of action for vasopressin is approximately two hours, however our patient showed response within 15 minutes, demonstrating its potential.[1] After the initial onset of shock, endogenous stores of antidiuretic hormone are consumed and the vasodilatory mechanisms of shock may propagate.[3] Vasopressin itself may reverse some of the vasodilatory changes induced in shock, and in combination with other pressors may prove to be of greater benefit than that of pressors alone.[2] CONCLUSIONS: In the setting of shock with limited intravenous access, intramuscular vasopressin may be an effective option for initial stabilization until IV access is obtained. REFERENCE #1: Brostoff J, James VH, Landon J. Plasma corticosteroid and growth hormone response to lysine-vasopressin in man. J Clin Endocrinol Metab. 1968;28(4):511-518. REFERENCE #2: Forrest P. Vasopressin and shock. Anaesth Intensive Care. 2001;29(5):463-472. REFERENCE #3: Russell JA. Bench-to-bedside review: Vasopressin in the management of septic shock. Crit Care. 2011;15(4):226. DISCLOSURES: No relevant relationships by George Apergis, source=Web Response No relevant relationships by Dushyant Damania, source=Web Response No relevant relationships by Aaron Douen, source=Web Response No relevant relationships by Jean Mallipudi, source=Web Response No relevant relationships by George Mbolu, source=Web Response No relevant relationships by Ryan Panetti, source=Web Response

SAT-432 MTD201 Has a Favourable 28-Day Sustained Release Profile Compared to Sandostatin LAR in Healthy Subjects

A double-blind, randomised, single-dose parallel group study was performed to compare the tolerability, pharmacokinetics and pharmacodynamics of MTD201 30 mg octreotide (test product) and Sandostatin LAR 30 mg (reference product) in healthy subjects. MTD201 uses Q-Sphera™ printing technology to precisely control microparticle size, which facilitates simpler reconstitution and injection using smaller needle size than Sandostatin LAR (SLAR) or Somatuline Autogel. MTD201 is being developed for acromegaly and NETs as an alternative to these existing long-acting treatments. Methods: 24 male and female healthy subjects were randomised to receive a single, 30mg i.m. injection of MTD201 (N=12) using a 21G needle or Sandostatin LAR (N=12) using the pre-packed 19G needle. Plasma samples for determination of octreotide, growth hormone (GH) and IGF-1 concentrations were obtained throughout the 63-day period after injection. The plasma GH response to a GHRH+arginine challenge, an accepted surrogate efficacy endpoint for somatostatin analogues, was performed 7 days before octreotide dosing and repeated 28- and 45-days post-dose. Additional data were collected to check for presence of anti-octreotide antibodies and injection site reactions were scored regularly for 7 days post-injection. Results: Both treatments were well tolerated, with AEs consistent with octreotide treatment. Overall plasma octreotide exposures for the test and reference drugs were comparable whilst subjects receiving MTD201 illustrated lower initial spike in plasma octreotide (burst; 0.12ng/mL and 0.99ng/mL for MTD201 and SLAR, respectively), a more linear, consistent profile, and lower variability across the intended dose interval (28 days). Both treatment groups showed detectable plasma octreotide levels up to the final PK sampling point of 63 days. GH and IGF-1 suppression were highly comparable across treatments, with ≈25% and ≈30% reductions from baseline for both groups, respectively. Injection site reactions were less frequent and of lower severity in subjects who received MTD201. Specifically, pain at the injection site was observed in 8% (MTD201) and 25% (SLAR) of subjects, and injection site tenderness in 8% (MTD201) and 83% (SLAR) of subjects. Conclusions: MTD201 produced a safe and effective sustained-release profile of octreotide, supporting a once-monthly treatment interval, as is indicated for SLAR. Therapeutic octreotide concentrations and GH/IGF-1 suppression comparable with SLAR were achieved. Combined with the other advantages for MTD201 regarding smaller needle size, simpler and more reliable reconstitution and injection, these results warrant further study in a suitably powered clinical trial to formally establish MTD201 as an alternative long-acting somatostatin analogue product.

Opioid Receptor Blockade with Intranasal Naloxone Prevents the Development of Hypoglycemia-Associated Autonomic Failure

Attainment of near-normal glycemic goals in type 1 diabetes (T1D) is limited by iatrogenic hypoglycemia. Repeated episodes of hypoglycemia lead to Hypoglycemia-Associated Autonomic Failure (HAAF), with blunted counter-regulatory hormone responses. We previously reported that pharmacologic activation of opioid receptors experimentally recapitulates some features of HAAF (Diabetes 66:2764; 2017), and opioid antagonism with intravenous naloxone prevents experimentally induced HAAF in healthy subjects. We therefore hypothesized that intranasal naloxone would augment central blockade of opioid receptors by bypassing the blood-brain barrier, and would provide a feasible outpatient approach to prevent HAAF. Using a randomized, double-blinded placebo-controlled study design, 7 healthy subjects (7M; age 43±3 year; BMI 25.9±0.9 kg/m2) participated in paired two-day studies, 5 weeks apart. Day 1 consisted of two 120 minute hypoglycemic (∼54 mg/dl) hyperinsulinemic clamps, with hourly intranasal administration of either saline (placebo) or naloxone (4 mg hourly). On day 2, subjects underwent one 120 minute hypoglycemic clamp (∼54 mg/dl). As expected, HAAF was experimentally induced in the placebo studies, based on lower peak epinephrine levels (mean±SEM: first hypoglycemic episode=1375±182 vs. third episode=858±235, pg/ml, p=0.004). With intranasal naloxone, epinephrine levels did not differ from the first to the third hypoglycemic episode (first=942±190 vs. third episode=857±134 pg/ml, p=0.4). Naloxone did not alter the responses of plasma glucagon, cortisol or growth hormone, or hypoglycemic symptoms. These findings suggest that HAAF can be prevented by acute blockade of opioid receptors during hypoglycemia, presumably by inhibiting opioid receptor activation by circulating endorphins. Thus, acute self-administration of intranasal naloxone could be an effective and feasible ’real-world’ approach to ameliorate HAAF in T1D. Disclosure S. Aleksic: None. E. Lontchi-Yimagou: None. R. Hulkower: None. M. Carey: None. M. Ude: None. W.G. Mitchell: None. O. Sandu: None. N. Tomuta: None. H. Shamoon: None. M. Hawkins: None.

Effect of antecedent moderate-intensity exercise on the glycemia-increasing effect of a 30-sec maximal sprint: a sex comparison.

This study investigated whether a prior bout of moderate-intensity exercise attenuates the glycemia-increasing effect of a maximal 30-sec sprint. A secondary aim was to determine whether the effect of antecedent exercise on the glucoregulatory response to sprinting is affected by sex. Participants (men n = 8; women n = 7) were tested on two occasions during which they either rested (CON) or cycled for 60-min at a moderate intensity of ~65% (EX) before performing a 30-sec maximal cycling effort 195 min later. In response to the sprint, blood glucose increased to a similar extent between EX and CON trials, peaking at 10 min of recovery, with no difference between sexes (P > 0.05). Blood glucose then declined at a faster rate in EX, and this was associated with a glucose rate of disappearance (Rd) that exceeded the glucose rate of appearance (Ra) earlier in EX compared with CON, although the overall glucose Ra and Rd profile was higher in men compared with women (P < 0.05). The response of growth hormone was attenuated during recovery from EX compared with CON (P < 0.05), with a lower absolute response in women compared with men (P < 0.05). The response of epinephrine and norepinephrine was also lower in women compared with men (P < 0.05) but similar between trials. In summary, a prior bout of moderate-intensity exercise does not affect the magnitude of the glycemia-increasing response to a 30-sec sprint; however, the subsequent decline in blood glucose is more rapid. This blood glucose response is similar between men and women, despite less pronounced changes in glucose Ra and Rd, and a lower response of plasma catecholamines and growth hormone to sprinting in women.

Effects of Antecedent GABA A Receptor Activation on Counterregulatory Responses to Exercise in Healthy Man.

The aim of this study was to determine whether antecedent stimulation of γ-aminobutyric acid (GABA) A receptors with the benzodiazepine alprazolam can blunt physiologic responses during next-day moderate (90 min) exercise in healthy man. Thirty-one healthy individuals (16 male/15 female aged 28 ± 1 year, BMI 23 ± 3 kg/m2) were studied during separate, 2-day protocols. Day 1 consisted of morning and afternoon 2-h hyperinsulinemic-euglycemic or hypoglycemic clamps with or without 1 mg alprazolam given 30 min before a clamp. Day 2 consisted of 90-min euglycemic cycling exercise at 50% VO2max. Despite similar euglycemia (5.3 ± 0.1 mmol/L) and insulinemia (46 ± 6 pmol/L) during day 2 exercise studies, GABA A activation with alprazolam during day 1 euglycemia resulted in significant blunting of plasma epinephrine, norepinephrine, glucagon, cortisol, and growth hormone responses. Lipolysis (glycerol, nonesterified fatty acids) and endogenous glucose production during exercise were also reduced, and glucose infusion rates were increased following prior euglycemia with alprazolam. Prior hypoglycemia with alprazolam resulted in further reduction of glucagon and cortisol responses during exercise. We conclude that prior activation of GABA A pathways can play a significant role in blunting key autonomous nervous system, neuroendocrine, and metabolic physiologic responses during next-day exercise in healthy man.

Effects of β-Hydroxy-β-methylbutyrate Free Acid Ingestion and Resistance Exercise on the Acute Endocrine Response.

Objective. To examine the endocrine response to a bout of heavy resistance exercise following acute β-hydroxy-β-methylbutyrate free acid (HMB-FA) ingestion. Design. Twenty resistance trained men were randomized and consumed either 1 g of HMB-FA (BetaTor) or placebo (PL) 30 min prior to performing an acute heavy resistance exercise protocol. Blood was obtained before (PRE), immediately after (IP), and 30 min after exercise (30P). Circulating concentrations of testosterone, growth hormone (GH), insulin-like growth factor (IGF-1), and insulin were assayed. Data were analyzed with a repeated measures ANOVA and area under the curve (AUC) was analyzed by the trapezoidal rule. Results. The resistance exercise protocol resulted in significant elevations from PRE in testosterone (P < 0.01), GH (P < 0.01), and insulin (P = 0.05) at IP, with GH (P < 0.01) and insulin (P < 0.01) remaining elevated at 30P. A significant interaction was noted between groups in the plasma GH response at IP, which was significantly higher following HMB-FA compared to PL (P < 0.01). AUC analysis revealed an elevated GH and IGF-1 response in the HMB-FA group compared to PL. Conclusion. HMB-FA prior to resistance exercise augments the GH response to high volume resistance exercise compared to PL. These findings provide further support for the potential anabolic benefits associated with HMB supplementation.

Growth hormone (GH)-releasing activity of chicken GH-releasing hormone (GHRH) in chickens

Two peptides with sequence similarities to growth hormone releasing hormone (GHRH) have been identified by analysis of the chicken genome. One of these peptides, chicken (c) GHRH-LP (like peptide) was previously found to poorly bind to chicken pituitary membranes or to cloned and expressed chicken GHRH receptors and had little, if any, growth hormone (GH)-releasing activity in vivo or in vitro. In contrast, a second more recently discovered peptide, cGHRH, does bind to cloned and expressed cGHRH receptors and increases cAMP activity in transfected cells. The possibility that this peptide may have in vivo GH-releasing activity was therefore assessed. The intravenous (i.v.) administration of cGHRH to immature chickens, at doses of 3–100μg/kg, significantly increased circulating GH concentrations within 10min of injection and the plasma GH levels remained elevated for at least 30min after the injection of maximally effective doses. The plasma GH responses to cGHRH were comparable with those induced by human (h) or porcine (p) GHRH preparations and to that induced by thyrotropin releasing hormone (TRH). In marked contrast, the i.v. injection of cGHRH-LP had no significant effect on circulating GH concentrations in immature chicks. GH release was also increased from slaughterhouse chicken pituitary glands perifused for 5min with cGHRH at doses of 0.1μg/ml or 1.0μg/ml, comparable with GH responses to hGHRH1–44. In contrast, the perifusion of chicken pituitary glands with cGHRH-LP had no significant effect on GH release. In summary, these results demonstrate that cGHRH has GH-releasing activity in chickens and support the possibility that it is the endogenous ligand of the cGHRH receptor.

Effects of a Pre-Exercise Meal on Plasma Growth Hormone Response and Fat Oxidation during Walking

The purpose of this study was to determine the effects of a pre-exercise meal on the plasma human growth hormone (hGH) response and fat oxidation during walking. Subjects (n=8) were randomly provided with either 1 g/kg body weight of glucose in 200 mL water (CHO) or 200 mL water alone (CON) 30 min prior to exercise and subsequently walked on a treadmill at 50% of VO2max for 60 min. Plasma hGH concentrations were significantly higher in subjects who received CHO compared to those who received CON at 15 and 30 min. The fat oxidation rate in the CHO was significantly lower than the CON while walking for 5~15, 25~35 and 45~55 min. Plasma FFA levels were also significantly lower in the CHO compared to the CON at 30, 45 and 60 min. Plasma glucose levels in the CHO were significantly lower while plasma insulin levels were significantly higher than in the CON at 15 and 30 min. Therefore, the results of this study suggest that the elevation of plasma hGH levels due to the intake of a pre-exercise meal may not be strongly related to fat oxidation and plasma free fatty acid (FFA) levels during low-intensity exercise.

A higher response of plasma neuropeptide Y, growth hormone, leptin levels and extracellular glycerol levels in subcutaneous abdominal adipose tissue to Acipimox during exercise in patients with bulimia nervosa: single-blind, randomized, microdialysis study

BackgroundNeuropeptide Y (NPY) is an important central orexigenic hormone predominantly produced by the hypothalamus, and recently found to be secreted in adipose tissue (AT). Acipimox (Aci) inhibits lipolysis in AT and reduces plasma glycerol and free fatty acid (FFA) levels. Exercise and Aci are enhancers of growth hormone (GH) and NPY secretion and exercise may alter leptin levels. We expect to find abnormal neuropeptidergic response in plasma and AT in patients with bulimia nervosa (BN). We hypothesize that Aci influences these peptides via a FFA-independent mechanism and that Aci inhibits lipolysis through a cyclic adenosine monophosphate (cAMP)-dependent pathway. Dysregulations of the AT-brain axis peptides might be involved in binge eating as is the case in BN.MethodsThe objective of this study was to determine the responses of plasma NPY, GH, leptin, FFA and glycerol levels to exercise in BN patients and healthy women (C) given the anti-lipolytic drug Aci or placebo. The secondary objective of this study was to compare the responses of extracellular glycerol levels and plasma glycerol levels to exercise alone or together with Aci administration in BN patients and C women. Extracellular glycerol was measured in vivo in subcutaneous (sc) abdominal AT using microdialysis. Eight BN and eight C women were recruited for this single-blind, randomized study. Aci or placebo was given 1 hour before the exercise (45 min, 2 W/kg of lean body mass [LBM]). NPY, GH, leptin, FFA, glycerol plasma and AT glycerol levels were measured using commercial kits.ResultsThe primary outcome of this study was that the exercise with Aci administration resulted in plasma NPY and GH increase (after a 45-minute exercise) and leptin (after a 90-minute post-exercise recovering phase) increased more in BN patients. The secondary outcomes of this study were that the exercise with Aci administration induced a higher decrease of extracellular glycerol in BN patients compared to the C group, while the exercise induced a higher increase of glycerol concentrations in sc abdominal AT of BN patients. Plasma glycerol levels decreased more in BN patients and plasma FFA levels were depressed in both groups after the exercise with Aci administration. The exercise induced similar increases in plasma NPY, GH, FFA and glycerol levels, and a similar decrease in the plasma leptin level in both groups.ConclusionsWe confirm the results of a single-blind, randomized, microdialysis study, i.e. that the Aci-induced elevation in plasma NPY and GH levels during the exercise is higher in BN patients and that Aci increased plasma leptin levels in the post-exercise recovering phase (90-minute) more in BN patients. The post-exercise rise (45-minute) in AT glycerol is much more attenuated by acute Aci treatment in BN patients. Simultaneously, we found facilitated turnover of plasma glycerol after the exercise together with Aci administration in BN. Our results support the hypotheses that Aci exerts an effect on the FFA-independent and cAMP-dependent mechanism.Trial RegistrationAustralia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000955910

Acipimox during exercise points to an inhibitory feedback of GH on ghrelin secretion in bulimic and healthy women

ObjectiveGhrelin is predominantly produced by the stomach and the growth hormone (GH)-ghrelin feedback loop between the stomach and the pituitary gland has recently been suggested. The disruption of the gut-brain axis might be involved in bulimia nervosa (BN). MethodsWe investigated responses of plasma GH, ghrelin, and neuropeptide Y (NPY) concentrations to exercise or to exercise after the administration of the antilipolytic drug Acipimox (Aci) in seven BN patients and seven healthy women (C). Aci was administered 1h before exercise (45min, 2W/kg of lean body mass/LBM/). Ghrelin, GH, NPY, free fatty acids (FFA) and glycerol plasma levels were measured during the test using commercial kits. ResultsThe exercise induced an increase in plasma GH, NPY and FFA in both groups and a decrease in plasma ghrelin levels only in BN patients. Exercise after Aci administration resulted in an increase in plasma GH, and a decrease in plasma ghrelin in both groups; NPY increased more in BN patients. Exercise-induced FFA increase was depressed after Aci. ConclusionsWe conclude that the Aci-induced suppression in plasma ghrelin levels during exercise in both groups suggests a negative feedback of GH on ghrelin secretion. Observed changes in plasma FFA levels were not related to changes in GH and ghrelin levels.

Difference in growth hormone response to growth hormone-releasing hormone (GHRH) testing following GHRH subacute treatment in normal aging and growth hormone-deficient adults: Possible perspectives for therapeutic use of GHRH or its analogs in elderly subjects?

The somatotroph axis function shows a decline in the elderly (somatopause). In particular growth hormone (GH) response to GH-releasing hormone (GHRH) is reduced in aged man but less than that observed in GH-deficient adults (GHDAs). Plasma GH response to GHRH (1 µg/kg BW) was significantly lower in four GHDAs than in seven healthy aged men 30, 60, and 90 min after acute GHRH administration. To verify whether a priming regimen might be able to increase the reduced GH response to GHRH, both healthy aged men and GHDA patients underwent repetitive administration of GHRH (100 µg GHRH intravenously as a single morning dose, every 2 days for 12 days). After the GHRH-priming regimen, plasma GH values 30, 60, and 90 min after the acute GHRH test were significantly higher than values at the corresponding time points before priming regimen in healthy aged men but not in GHDA patients. These findings confirmed that somatotroph cells become less sensitive to GHRH with normal aging and demonstrate that repetitive administration of GHRH restores the attenuated response only in healthy aged men but not in GHDA patients. This could support the possible use of GHRH or its analogs instead of recombinant human GH in elderly patients with the advantage of preserving the endogenous pulses of GH with the secretion of the different isoforms of GH. However, concerns arise about the possible role of these molecules in tumorigenesis and tumor growth promotion.

Acute salinity challenges in Mozambique and Nile tilapia: Differential responses of plasma prolactin, growth hormone and branchial expression of ion transporters

The responses of Mozambique and Nile tilapia acclimated to fresh water (FW) and brackish water (BW; 17‰) were compared following acute salinity challenges. In both species, plasma osmolality increased to above 450 mOsm by 2 h after transfer from FW to seawater (SW); these increases in osmolality were accompanied by unexpected increases in plasma prolactin (PRL). Likewise, PRL receptor gene expression in the gill also increased in both species. In Nile tilapia, hyperosmotic transfers (FW to BW and SW) resulted in increased plasma growth hormone (GH) and in branchial GH receptor gene expression, responses that were absent in Mozambique tilapia. Branchial gene expression of osmotic stress transcription factor 1 (OSTF1) increased in both species following transfer from FW to SW, whereas transfer from BW to SW induced OSTF1 expression only in the Nile tilapia. Branchial expression of Na +/Cl − cotransporter was higher in FW in both species than in BW. Branchial gene expression of Na +/K +/2Cl − cotransporter (NKCC) increased after transfer from BW to SW in Mozambique tilapia, whereas expression was reduced in the Nile tilapia following the same transfer. The difference in the SW adaptability of these species may be related to a limited capacity of Nile tilapia to up-regulate NKCC gene expression, which is likely to be an essential component in the recruitment of SW-type chloride cells. The differential responses of GH and OSTF1 may also be associated with the disparate SW adaptability of these two tilapiine species.

Endogenous ghrelin released in response to endothelin stimulates growth hormone secretion in cattle

The purpose of this study was to evaluate whether circulating ghrelin and growth hormone (GH) concentrations in cattle are regulated by endothelin-1 (ET-1), endothelin-3 (ET-3), and secretin. Six Holstein steers (242 ± 1 d old, 280.5 ± 4.4 kg body weight [BW]; mean ± SEM) were allocated randomly in an incomplete Latin square design to receive each of 4 treatment compounds (vehicle, ET-1, ET-3, and secretin) with 1-d intervals between successive treatments. The treatment compounds were injected intravenously via a catheter inserted into the external jugular vein of each steer. Blood was sampled from the indwelling catheter at -30, -15, 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, and 180 min. Plasma ghrelin and GH responses to the treatment compounds were measured by a double-antibody radioimmunoassay system. Data were analyzed by using a MIXED procedure of SAS, version 9.1. Plasma acyl ghrelin, total ghrelin, and GH concentrations were increased by both ET-1 and ET-3 injection (ET-1 injection: 311 ± 15 pg/mL vs 245 ± 15 pg/mL, 2.4 ± 0.2 ng/mL vs 1.61 ± 0.05 ng/mL, 4.73 ± 0.92 ng/mL vs 1.17 ± 0.09 ng/mL for acyl ghrelin, total ghrelin, and GH, respectively; ET-3 injection: 337 ± 27 pg/mL vs 245 ± 15 pg/mL, 2.6 ± 0.1 ng/mL vs 1.61 ± 0.05 ng/mL, 5.56 ± 0.97 ng/mL vs 1.17 ± 0.09 ng/mL for acyl ghrelin, total ghrelin, and GH, respectively; P < 0.01). Ghrelin and GH concentrations were not changed by secretin injection throughout the experimental periods. These results indicate that ET-1 and ET-3 stimulate ghrelin and GH secretion in cattle and demonstrate for the first time that endogenous ghrelin released in response to endothelin injection stimulates GH secretion in vivo in cattle.

Effect of l-dopa on growth hormone, glucose, insulin, and cortisol response in obese subjects.

Plasma growth hormone, glucose, insulin and cortisol response to oral administration of L-dopa and in insulin-tolerance test were investigated in 18 obese subjects. The results were compared with the results obtained in 10 normal subjects. The obese subjects displayed a lack of growth hormone responsiveness to L-dopa and a diminished GH responsiveness to hypoglycemia. There was no significant difference in glucose response to hypoglycemia in normal and obese subjects. Obese subjects showed normal increments of plasma cortisol following induction of hypoglycemia although there was no consistent cortisol response after L-dopa administration. A blood glucose response following L-dopa administration was seen in most of normal subjects while no increment of blood glucose was noticed in obese subjects.

Role for des-acyl ghrelin in the responsiveness of plasma hormones and metabolites to ghrelin in Holstein steers

Gastric-derived peptide hormone ghrelin is known for its potent growth hormone (GH) stimulatory effects. The acyl-modification on N-terminal Ser 3 residue is reported to be important to stimulate the ghrelin receptor, GH secretagogue-receptor type1a (GHS-R1a). However, major portion of circulating ghrelin lacks in acylation, and some biological properties of des-acyl ghrelin have been reported in monogastric animals. In the present study, the responsiveness of plasma hormones and metabolites to ghrelin in steers was characterized, and role for des-acyl ghrelin in these changes was investigated. The repeated intravenous administrations of bovine ghrelin (1.0 μg/kg BW) every 2 h for 8 h to Holstein steers significantly increased the plasma acylated ghrelin, total ghrelin, GH, insulin and NEFA levels. The GH responses in peak values and area under the curves (AUCs) were attenuated by repeated injections of ghrelin, however, the responses of plasma total ghrelin were similar. Plasma insulin AUC decreased after fourth injection of ghrelin while plasma NEFA AUCs gradually increased by repeated injections of ghrelin. Pretreatment of des-acyl ghrelin (10.0 μg/kg BW) 5 min prior to the single injection of ghrelin (1.0 μg/kg BW) did not affect the ghrelin-induced hormonal changes. Moreover, the responses of plasma GH to bovine and porcine ghrelin, which differ in C-terminal amino acid residues, were similar in calves. These data show that (1) GH release was attenuated by repeated administration of ghrelin, (2) ghrelin regulates glucose and fatty acid metabolism probably via different pathway, and (3) des-acyl ghrelin is unlikely the antagonist for ghrelin to induce endocrine effects in Holstein steers.

Plasma growth hormone response to oral clonidine as compared to insulin hypoglycemia in obese children and adolescents.

The response of plasma growth hormone (hGH) to a single oral dose of clonidine (0.15 mg/m2) was compared with that obtained with insulin hypoglycemia (ITT) induced by administration of double the usual dose (0.2 U/kg i.v.) in 13 obese subjects aged 5-17 years (7 males, 6 females) with a subscapular skinfold greater than 20 mm and a weight greater than 2 SD of the median. Six healthy subjects (3 males, 3 females), aged 8-14 years who served as controls received the usual dose of 0.1 U/kg i.v. in the ITT. Clonidine induced an increase of more than 10 ng/ml in the plasma hGH levels in 10 (4 males, 6 females) of the 13 obese subjects and in all of the healthy controls, with peak levels ranging from 14.3 to 31.0 ng/ml (m +/- SD 21.0 +/- 5.2 ng/ml); the ITT elicited a similar rise in only 6 of the 13 subjects and 3 of the healthy controls, with peak levels ranging from 9.8 to 20.0 ng/ml (m +/- SD 14.4 +/- 4.5 ng/ml). Clonidine decreased plasma insulin levels in all the obese female subjects (by a mean of 65%) whereas in the obese males the insulin pattern was variable. There was no change in blood glucose levels following the administration of clonidine; during the ITT all subjects showed a decrease to less than 50 mg/dl. Blood pressure decreased by a mean of 20 mmHg during the clonidine test. This study demonstrates that clonidine is a more effective hGH stimulus than insulin induced hypoglycemia in normal and in obese children and that the lower hGH secretion of the obese is confirmed by the clonidine test.

Influence of oral contraceptive use on growth hormone in vivo bioactivity following resistance exercise: Responses of molecular mass variants

The purpose was to examine effects of oral contraceptive (OC) use on plasma growth hormone (GH) responses to heavy resistance exercise. Sixty untrained women were placed into one of two groups: currently using OC (Ortho Tri-Cyclen®) (n=25; mean±SD: 24.5±4.2y, 160.4±7.1cm, 64.1±11.3kg) or not currently using OC (NOC) (n=35; 23.6±4.6y, 165.9±6.0cm, 65.7±10.3kg). Participants performed an acute heavy resistance exercise test (AHRET; six sets of 10 repetition squats; 2min rest between sets) during days 2–4 of the follicular phase (NOC group) or of inactive oral contraceptive intake (OC group). Plasma was obtained before and immediately after AHRET and subsequently fractionated based on apparent molecular weight (>60kD, 30–60kD, and <30kD). GH was determined in unfractionated plasma and each plasma fraction using 4 methods: (1) Nichols Institute Diagnostics immunoradiometric assay (Nichols), (2) National Institute of Diabetes and Digestive Kidney Diseases (NIDDK) competitive radioimmunoassay, (3) DSL immunofunctional enzyme-linked immunoabsorbent assay (IFA) and (4) rat tibial line bioassay. GH increased (P<0.05) in all fractions post-AHRET for the Nichols, NIDDK, and IFA. The OC group displayed higher resting GH for the NIDDK, and higher exercise-induced GH for the IFA, Nichols, and NIDDK in unfractionated plasma and >60kD subfraction compared to NOC group. No differences were observed for the tibial line bioassay. OC use augmented immunological GH response to AHRET in unfractionated plasma and >60kD molecular weight subfraction. However, OC use only increased biological activity of GH in one of two bioassays. These data demonstrated that GH concentrations at rest and following exercise are assay-dependent.

Effects of growth hormone-releasing factor on growth hormone response, growth and feed conversion efficiency in buffalo heifers ( Bubalus bubalis)

The aim of this study was to determine the benefits of growth hormone-releasing factor (GRF) on growth and feed conversion efficiency (FCE) in buffaloes. Twelve Murrah buffalo heifers ( Bubalus bubalis) of mean age 24.8 months and mean body weight 302.4 kg were divided into two groups (treatment and control) with six animals in each group. The buffaloes were given intravenous injections of bovine GRF (bGRF) at a dose rate of 10 μg/100 kg body weight or an equal volume of saline at 15-day intervals for a period of 9 months. Plasma growth hormone (GH) responses to bGRF challenge were measured in blood samples collected at 90-day intervals on days 1, 90, 180 and 270 and samples were taken at −60, −30, 0, +10, +20, +30, +60, +120 and +180 min relative to bGRF injection. Blood samples were also collected weekly by jugular venepuncture for the quantification of plasma GH. The average growth rate (AGR) and FCE of all animals were recorded at 15-day intervals. Plasma GH concentrations increased ( P = 0.001) steadily following bGRF challenge, peaking 10–20 min after challenge and declining to baseline by 180 min. In the treatment group, there were no significant differences ( P > 0.05) in either the peak heights of the GH response or the area under the curve (AUC) of the GH response after bGRF challenge on any of the four occasions of intensive bleeding. There were overall increases in plasma GH concentrations ( P < 0.01), AGR ( P < 0.01) and FCE ( P = 0.05) in the treatment group compared with the control animals. The study showed that GH responsiveness to administration of bGRF at 15-day intervals over 9 months of treatment remained unchanged in buffalo heifers. Exogenous bGRF treatment for a long period can therefore enhance GH release leading to higher growth rates and better feed conversion efficiency in buffalo heifers.

Plasma growth hormone concentrations in female mithun (Bos frontalis) of different ages: relations with age and body weight

The role of growth hormone (GH) in postnatal somatic growth is well established. Its basal level and relation to growth performance in different age group mithun (Bos frontalis), a semiwild ruminant has not been characterized until now. To estimate the normal blood GH level and also to assess the influence of age and body weight (BW) on blood GH level in captive mithuns, a total of 65 female mithuns was divided into six age groups (group I, 0-6 months; group II, >6-12 months; group III, >1-2 years; group IV, >2-2.5 years; group V, >2.5-3.0 years and group VI, >3.0 years). Blood samples collected weekly for six consecutive weeks were assayed for GH. GH was also estimated in the samples collected from six growing mithuns at -60, -45, -30, -15, -10, -5 and 0 min prior to GH-releasing hormone (GHRH) administration for calculation of basal GH level and at 5, 10, 15, 30 min and thereafter at 15-min interval up to 8 h post-GHRH to assess blood GH response following GHRH administration in growing mithuns. For calculation of basal plasma GH in adult mithuns, GH was measured in blood samples collected at 30-min interval for 24 h from four animals. BW of all animals was recorded on two consecutive days per week and average of weekly BW was considered for growth rate calculation. It was found that both mean GH and GH per 100 kg BW between the age groups differ (p < 0.01). With increasing age and BW, GH and GH per 100 kg BW both decreased (p < 0.01). The age group with higher plasma GH and GH per 100 kg BW showed higher growth rates (r = 0.83 and 0.97 respectively). Interestingly, mean plasma GH for six consecutive weeks in all the groups showed much greater GH concentration (group I, 86.6 +/- 9.7 ng/ml to group VI 33.2 +/- 5 ng/ml) than reported in other species. Mean basal plasma GH calculated in growing and adult mithuns was 29.6 +/- 4.01 ng/ml and around 25 +/- 3.6 ng/ml respectively. The GH peak (444 +/- 21.3 ng/ml) was registered at 15 min post-GHRH administration in growing mithuns. In conclusion, age and BW influence plasma GH and GH per 100 kg BW but the latter is a better indicator of growth. The basal plasma GH and GH response to GHRH administration is six to eight and four to five times higher in mithun than in other species reported so far. An accurate assessment of the relationship between GH profiles and protein metabolism, proper receptor level study for GH action at the cellular level and the interaction of GH with other growth factors awaits better understanding of higher GH in this unique species.