Increase In Growth Hormone Research Articles

Regulation of Gill Cytosolic Corticosteroid Receptors in Juvenile Atlantic Salmon: Interaction Effects of Growth Hormone with Prolactin and Triiodothyronine

The potential effects of growth hormone (GH), prolactin (Prl), and triiodothyronine (T3) on gill Na+,K+-ATPase activity and corticosteroid receptor (CR) concentration (Bmax) and dissociation constant (Kd) were examined in juvenile Atlantic salmon (Salmo salar). Compared to controls, fish injected with GH (ovine, 5.0 μg g−1) had significantly greater gill Na+,K+-ATPase activity after 7 and 14 days. Gill CRBmaxandKdwere significantly elevated on day 7, but not day 14. T3also significantly increased CRBmax. The effect of GH on CRBmaxwas also additive with T3(5.0 μg g−1) treatment. There was a synergistic effect on CRBmaxwhen purified coho salmon GH (csGH, 0.1 μg g−1) was injected in combination with T3(1.6 μg g−1). Prl (ovine, 5.0 μg g−1; purified coho salmon, 0.1 μg g−1) did not significantly alter gill CRBmax. Although Prl limited the increase in CRBmaxby GH, the effect was not signicant. T3and Prl did not have an effect onKd. GH significantly increased gill Na+,K+-ATPase activity, T3administration did not have a significant effect, and Prl-treated fish had significantly lower gill Na+,K+-ATPase activity. The results indicate that T3acts additively with GH, while Prl has no effect in regulating CRBmax. An increase in cytosolic CR by GH and T3, but not Prl, may regulate gill responsiveness to cortisol and be an important mechanism in the endocrine control of physiological changes during the parr–smolt transformation.

Effect of Ergotamine on Serotonin-Mediated Responses in the Rodent and Human Brain

In the rat dorsal hippocampus and dorsal raphe nucleus, the microiontophoretic application of ergotamine and 5-HT suppressed the firing activity of CA3 pyramidal neurons and 5-HT neurons, an effect antagonized by selective 5-HT1A receptor antagonists. Co-application of ergotamine prevented the inhibitory action of 5-HT on the firing activity of CA3 pyramidal neurons but not of 5-HT neurons, indicating that ergotamine acted as a partial 5-HT1A receptor agonist in the dorsal hippocampus and as a full agonist at 5-HT1A autoreceptors. Ergotamine decreased, in a concentration-dependent manner, the electrically evoked release of [3H]5-HT in preloaded rat and guinea pig hypothalamus slices; this effect was prevented by the nonselective 5-HT receptor antagonist methiothepin but not by the selective 5-HT1B/1D receptor antagonist GR 127935 or the α2-adrenoceptor antagonist idazoxan. Although body temperature in humans remained unchanged following inhaled ergotamine, in the rat, subcutaneously injected ergotamine produced a hypothermia that was prevented by a pretreatment with the 5-HT1A/1B receptor/β-adrenoceptor antagonist pindolol. Finally in humans, ergotamine did not alter prolactin or adrenocorticotropic hormone levels, but increased growth hormone level, which was prevented by pindolol. Cortisol level was increased in humans by ergotamine, but this enhancement was unaltered by pindolol. In conclusion, the present results suggest that ergotamine acted in the rat brain as a 5-HT1A receptor agonist and as an agonist of terminal 5-HT autoreceptor of a yet undefined subtype. In humans, ergotamine also displayed some 5-HT1A receptor activity but, probably because of lack of receptor selectivity, it did not present the same profile as other 5-HT1A receptor agonists.

Circulating growth hormone levels in Atlantic salmon smolts following seawater transfer: effects of photoperiod regime, salinity, duration of exposure and season

Atlantic salmon juveniles in fresh water, both on simulated natural photoperiod (LDN) and continuous light (LL) regime, were transferred to fresh water (controls) and different salinities (28, 35 and 40‰) at five different dates over the period of parr-smolt transformation (February to June). Survival was noted and plasma samples obtained after 12, 24, 48, 96 and 192 h of salinity exposure. Survival and plasma sodium levels were used to assess hypoosmoregulatory ability, and plasma growth hormone (GH) levels measured to elucidate the possible role of this hormone in the salinity tolerance of smolting salmon. The fish on LDN photoperiod had markedly elevated plasma GH levels as well as improved hypoosmoregulatory ability in June, whereas these changes were inhibited by the LL regime. Salinity exposure caused a transient increase in circulating GH levels. The response was complex, both in regard to the date of exposure, the photoperiod regime, and the level of salinity. The data indicate that elevated plasma GH levels in smolting Atlantic salmon in freshwater are of importance for the subsequent hypoosmoregulatory ability in seawater. However, it is questioned whether the transient increase in GH following salinity exposure represents a specific short-term hypoosmoregulatory role.

Pituitary and Extrapituitary Action Sites of the Novel Nonpeptidyl Growth Hormone (GH) Secretagogue L-692,429 in the Chicken

Chickens were used as a model to further analyze the efficacy and specificity of L-692,429, a novel nonpeptidyl mimic of growth hormone (GH)-releasing peptide-6 (GHRP-6), which is a specific GH-releasing secretagogue in mammals. Actions at the level of the pituitary and the hypothalamus were studied. Pituitaries isolated from 1-day-old (C1) chicks responded in a dose-dependent manner to L-692,429 (ED50=10 nM). Using equimolar concentrations of thyrotropin-releasing hormone (TRH), human GH-releasing hormone (hGHRH1–29), and L-692,429 (10 nM), L-692,429 had 20–25% thein vitropotency of the two endogenous releasing factors. There was an additive effect between hGHRH1–29(10 nM) and L-692,429 (10 or 100 nM) on GH release from C1 pituitaries but no such additive effect was observed when pituitaries were exposed to both TRH (10 nM) and L-692,429 (100 nM). An acute challenge with 50 μg L-692,429 resulted in increased plasma GH levels within 5 min, which remained elevated for up to 15 min (C1 chickens). This increase in GH was accompanied by a drop in hypothalamic TRH content by 5 min. Hypothalamic somatostatin (SRIH) content did not change. Plasma corticosterone concentrations were increased following L-692,429 treatment, whereas plasma α-subunit, T4, and T3levels were unchanged. To confirm the role of the decreased hypothalamic TRH concentrations in the GH-releasing activity of L-692,429 in the chicken, chickens (C1) were pretreated with normal rabbit serum (NRS) or a TRH antiserum (1/50) 1 h prior to the L-692,429 challenge. Both groups showed an increase in circulating GH but the increase was within 5 min inhibited by the TRH antiserum pretreatment, whereas no differences were noted in plasma corticosterone levels. It is concluded that in the chicken the GH secretagogue L-692,429 has a dual action site: (1) directly at the level of the pituitary and (2) centrally through an increase in hypothalamic TRH release.

Arginine increases insulin-like growth factor-I production and collagen synthesis in osteoblast-like cells

Protein-energy malnutrition, which is common in elderly patients with osteoporotic hip fractures, is associated with reduced plasma levels of insulin-like growth factor-I (IGF-I). IGF-I is an important regulator of bone metabolism, particularly of osteoblastic bone formation both in vivo and in vitro. Pharmacological doses of arginine (Arg) increase growth hormone (GH) and IGF-I serum levels. Whether amino acids, particularly Arg, can directly modulate the production of IGF-I by osteoblasts is not known. We investigated the effects of increasing concentrations of Arg on IGF-I expression and production, α 1(I) collagen expression and collagen synthesis, and cell proliferation and cell differentiation, as assessed by alkaline phosphatase (ALP) activity and osteocalcin (OC) release, in confluent mouse osteoblast-like MC3T3-E1 cells. The addition of Arg (7.5–7500 μmol/L, equivalent to 0.1- to 100-fold human plasma concentration) for 48 h increased IGF-I production (adjusted for cell number) in a concentration-dependent manner with a maximum of 2.3 ± 0.3-fold at 7500 μmol/L Arg [ x ± standard error of the mean (SEM), n = 3 experiments, p < 0.01]. Arg (7.5–7500 μmol/L) increased the percentage of de novo collagen synthesis in a concentration-dependent manner (2.1 ± 0.4-fold with 7500 μmol/L Arg, p < 0.001) and ALP activity with a maximal stimulation of 144% ± 13% plateauing at 750 μmol/L Arg ( p = 0.002). The steady state level of IGF-I messenger ribonucleic acid (mRNA) and α 1(I) collagen mRNA (both normalized to cyclophilin mRNA) of cells incubated with Arg at high (100-fold) or low (0.1-fold) human plasma concentrations, was 1.4 ± 0.2, 1.2 ± 0.2, and 1.1 ± 0.2 after 24 h for the 7.5, 1.8, and 0.9 kb IGF-I mRNA transcripts, respectively (n = 3 experiments) and 1.5 ± 0.2 and 3.1 ± 0.7 after 24 and 48 h, respectively, for the combined analysis of the 5.6 and 4.7 kb α 1(I) collagen mRNA transcripts (n = 3 experiments). A maximal mitogenic effect (cell number) of +21% ± 3% ( p < 0.01) was obtained with 1000 μmol/L Arg. In contrast, Arg (7.5–7500 μmol/L) induced a reduction of OC production, which reached 30% ± 3% with 7500 μmol/L Arg ( p = 0.02). In conclusion, Arg stimulated IGF-I production and collagen synthesis in osteoblast-like cells. Thus, Arg may influence bone formation by enhancing local IGF-I production.

Different effects of naloxone on the growth hormone response to melatonin and pyridostigmine in normal men

The effect of melatonin (MEL) (12 mg orally), pyridostigmine (60 mg orally), the combination of MEL and pyridostigmine, or placebo on growth hormone (GH) secretion was tested in seven normal men. In addition, MEL tests and pyridostigmine tests were repeated after pretreatment with naloxone (1.2-mg bolus followed by intravenous [IV] infusion of 1.6 mg/h for 3 hours). Serum GH levels increased fivefold after MEL and sixfold after pyridostigmine administration. The concomitant administration of MEL did not change the GH response to pyridostigmine. In the presence of naloxone, the GH response to MEL was completely abolished, whereas naloxone did not modify the pyridostigmine-induced GH increase. These data suggest that MEL and pyridostigmine stimulate GH secretion through a common mechanism, which is probably represented by the inhibition of somatostatin activity. However, in contrast to pyridostigmine, the action of MEL appears to be exerted through a naloxone-sensitive opioid mediation.

Endotoxin Injection Increases Growth Hormone and Somatostatin Secretion in Sheep

Endotoxin has been shown to stimulate GH secretion in human and sheep. However, changes in hypothalamic neurohormones involved in the GH regulation by endotoxin have never been studied in vivo. In sheep it is possible to collect hypophysial portal blood (HPB) and quantify GH-releasing hormone (GHRH) and somatostatin (SRIH) secretion under physiological conditions. The purpose of this study was to determine the effect of an acute iv endotoxin administration on the secretion of these peptides in sheep. Endotoxin induced a sustained increase of GH (×6.2 ± 1.3) in intact rams. This stimulation was delayed and less marked when compared with the hypothalamic-pituitary-adrenal axis. Surprisingly, the GH increase was associated with an important rise of jugular (×10.6± 2.4) and portal (×7.9 ± 3) SRIH levels, without a significant GHRH increase. To determine if the portal SRIH increase was a consequence of an increased short feedback of GH, we studied GH response to endotoxin after a previous GHRH injection to deplete the pituitary pools of GH. In that case, despite the absence of increase of GH after endotoxin treatment, SRIH levels was markedly increased. For the first time we have observed an experimental situation in sheep with a simultaneous and closed amplitude increase in jugular and portal SRIH. The source of jugular SRIH is likely the gastrointestinal tract and the increased jugular SRIH release in systemic circulation might be in part responsible for the increase of hypophysial portal SRIH. Ultimately our results show that endotoxin induced a complex reaction at multiple levels with a specific increase in both portal and peripheral SRIH levels. The surprising association of a lack of change in GHRH release and an increased secretion of SRIH with the increase of GH suggests that the effect of endotoxin on GH axis is mainly a pituitary one. The selective blockade of somatostatin should be useful for a better knowledge of the role of SRIH stimulation in the physiopathology of septic shock.

Endotoxin injection increases growth hormone and somatostatin secretion in sheep.

Endotoxin has been shown to stimulate GH secretion in human and sheep. However, changes in hypothalamic neurohormones involved in the GH regulation by endotoxin have never been studied in vivo. In sheep it is possible to collect hypophysial portal blood (HPB) and quantify GH-releasing hormone (GHRH) and somatostatin (SRIH) secretion under physiological conditions. The purpose of this study was to determine the effect of an acute i.v. endotoxin administration on the secretion of these peptides in sheep. Endotoxin induced a sustained increase of GH (x6.2 +/- 1.3) in intact rams. This stimulation was delayed and less marked when compared with the hypothalamic-pituitary-adrenal axis. Surprisingly, the GH increase was associated with an important rise of jugular (x10.6 +/- 2.4) and portal (x7.9 +/- 3) SRIH levels, without a significant GHRH increase. To determine if the portal SRIH increase was a consequence of an increased short feedback of GH, we studied GH response to endotoxin after a previous GHRH injection to deplete the pituitary pools of GH. In that case, despite the absence of increase of GH after endotoxin treatment, SRIH levels was markedly increased. For the first time we have observed an experimental situation in sheep with a simultaneous and closed amplitude increase in jugular and portal SRIH. The source of jugular SRIH is likely the gastrointestinal tract and the increased jugular SRIH release in systemic circulation might be in part responsible for the increase of hypophysial portal SRIH. Ultimately our results show that endotoxin induced a complex reaction at multiple levels with a specific increase in both portal and peripheral SRIH levels. The surprising association of a lack of change in GHRH release and an increased secretion of SRIH with the increase of GH suggests that the effect of endotoxin on GH axis is mainly a pituitary one. The selective blockade of somatostatin should be useful for a better knowledge of the role of SRIH stimulation in the physiopathology of septic shock.

The effects of short-term resistance training on endocrine function in men and women.

This investigation examined hormonal adaptations to acute resistance exercise and determined whether training adaptations are observed within an 8-week period in untrained men and women. The protocol consisted of a 1-week pre-conditioning orientation phase followed by 8 weeks of heavy resistance training. Three lower-limb exercises for the quadriceps femoris muscle group (squat, leg press, knee extension) were performed twice a week (Monday and Friday) with every other Wednesday used for maximal dynamic 1 RM strength testing. Blood samples were obtained pre-exercise (Pre-Ex), immediately post-exercise (IP), and 5 min post-exercise (5-P) during the first week of training (T-1), after 6 weeks (T-2) and 8 weeks (T-3) of training to determine blood concentrations of whole-blood lactate (LAC), serum total testosterone (TT), sex-hormone binding globulin (SHBG), cortisol (CORT) and growth hormone (GH). Serum TT concentrations were significantly (P < or = 0.05) higher for men at all time points measured. Men did not demonstrate an increase due to exercise until T-2. An increase in pre-exercise concentrations of TT were observed both for men and women at T-2 and T-3. No differences were observed for CORT between men and women; increases in CORT above pre-exercise values were observed for men at all training phases and at T-2 and T-3 for women. A reduction in CORT concentrations at rest was observed both in men and women at T-3. Women demonstrated higher pre-exercise GH values than men at all training phases; no changes with training were observed for GH concentrations. Exercise-induced increases in GH above pre-exercise values were observed at all phases of training. Women demonstrated higher serum concentrations of SHBG at all time points. No exercise-induced increases were observed in men over the training period but women increased SHBG with exercise at T-3. SHBG concentrations in women were also significantly higher at T-2 and T-3 when compared to T-1 values. Increases in LAC concentrations due to exercise were observed both for men and women for all training phases but no significant differences were observed with training. These data illustrate that untrained individuals may exhibit early-phase endocrine adaptations during a resistance training program. These hormonal adaptations may influence and help to mediate other adaptations in the nervous system and muscle fibers, which have been shown to be very responsive in the early phase of strength adaptations with resistance training.

PLASMA SUBSTRATE AND ENDOCRINE RESPONSES TO SUPPLEMENTATION DURING ENDURANCE EXERCISE.

1252 The interaction of substrates and hormones in response to protein consumption during exercise is unknown. This study was designed to characterize substrate and hormone changes with supplementation during endurance exercise. Nine male runners (23.2±.6 yr, VO2max 58.7 ml·kg-1·min-1) participated in 3 trials where a protein (PTN), carbohydrate (CHO), or placebo (PLA) drink was consumed during a 2-hr treadmill run at 65%VO2max. Hormones [insulin (IN), glucagon(GLN), epinephrine (EPI), norepinephrine (NE), growth hormone (GH), testosterone (T), cortisol (C)] and substrates [glucose (GLU), lactate (LAC), free fatty acids (FFA)] were measured pre- and post-exercise. Change values(mean±SE) are shown below. TableTableExcept for IN and C, hormones and substrates increased with exercise(P<.05). GLN and GH increases were greatest (P<.05) with PTN. CHO and PTN blunted (P<.05) FFA response. Respiratory exchange ratio decreased(P<.05) during the runs with PTN and PLA. Modest nutrient supplementation(≈ 174 kcal) throughout exercise can alter endocrine responses as well as substrate availability and utilization.

Two-Month Treatment of Obese Subjects with the Oral Growth Hormone (GH) Secretagogue MK-677 Increases GH Secretion, Fat-Free Mass, and Energy Expenditure1

Obesity is associated with blunted GH secretion, unfavorable body composition, and increased cardiovascular mortality. The objective of this study was to investigate the effects of oral treatment with the GH secretagogue MK-677 on GH secretion and body composition in otherwise healthy obese males. The study was randomized, double blind, parallel, and placebo controlled. Twenty-four obese males, aged 18-50 yr, with body mass indexes greater than 30 kg/m2 and waist/hip ratios greater than 0.95, were treated with MK-677 25 mg (n = 12) or placebo (n = 12) daily for 8 weeks. Serum insulin-like growth factor I (IGF-I) increased approximately 40% with MK-677 treatment (P < 0.001 vs. placebo). Serum IGF-binding protein-3 was also significantly increased (P < or = 0.001 vs. placebo). GH and PRL (peak and area under the curve values) were significantly increased after the initial dose of MK-677. Significant increases, with the exception of peak PRL, persisted at 2 and 8 weeks of treatment. The increases in GH and PRL after the initial dose were significantly greater than the increase seen after multiple doses. Serum and urinary concentrations of cortisol were not increased at 2 and 8 weeks (P = NS, vs. placebo). Fat-free mass increased significantly in the MK-677 treatment group when determined with dual energy x-ray absorptiometry (P < 0.01) or using a four-compartment model (P < 0.05). Total and visceral fat were not significantly changed with active therapy. The basal metabolic rate was significantly increased at 2 weeks of MK-677 treatment (P = 0.01) but not at 8 weeks (P = 0.1). Fasting concentrations of glucose and insulin were unchanged, whereas an oral glucose tolerance test showed impairment of glucose homeostasis at 2 and 8 weeks. We conclude that 2-month treatment with MK-677 in healthy obese males caused a sustained increase in serum levels of GH, IGF-I, and IGF-binding protein-3. The effects on cortisol secretion were transient. Changes in body composition and energy expenditure were of an anabolic nature, with a sustained increase in fat-free mass and a transient increase in basal metabolic rate. Further studies are needed to evaluate whether a higher dose of MK-677 or a more prolonged treatment period can promote a reduction in body fat.

Effectiveness of Growth Hormone (GH) Secretagogues in Diagnosing and Treating GH Secretory Deficiency in Aging Men

This study was conducted primarily to determine the utility of recombinant growth hormone releasing hormone (GHRH) and xenobiotic GH-releasing peptide (GHRP) administered sequentially or in combination, as diagnostic agents for pituitary-based, GH secretory dysfunction in aging men. The secondary purpose was to test the hypothesis that loss of sensitivity to stimulation with GHRH during aging results, at least in part, from reduced exposure of the pituitary gland to the yet unknown, endogenous compound whose activity is stimulated by GHRP. Increases in serum GH following GHRH administration were significantly lower in older men than they were in adolescent and young adult men. In contrast, changes in serum GH following GHRP were comparable in the younger and older men. Because robust GH secretion in response to administration of exogenous GHRH or GHRP is interpreted as representing adequate concentrations of complementary endogenous GHRP and GHRH, respectively, the data suggested that older subjects were ...

Glucoregulatory disorders in school refusal students

Our previous studies demonstrated autonomic nervous system disorders and cerebral blood hypoperfusion in school refusal students with underlying emotional distress due to fear or anxiety associated with school attendance. Because severe stress is known to affect glucoregulatory metabolism, this study used the oral glucose tolerance test (OGTT) to measure glucose metabolism in school refusal students. A three-hour OGTT was performed. In preparation for the test, students fasted overnight. After a fasting blood sample was drawn, students were given solutions containing a predetermined amount of glucose based on their body weight (1.75 g/kg to a maximum 75 g). After glucose ingestion, blood samples were drawn at 30, 60, 90, 120, 150, and 180 mm to measure blood glucose (BG), immunoreactive insulin (IRI), pancreatic glucagon (IRG) and growth hormone (GH) levels. BG levels, IRI response, cumulative BG (sigma BG), cumulative IRI (sigma IRI), insulin/glucose ratio (delta IRI/delta BG), and insulinogenic index (sigma IRI/sigma BG) were then compared to previously reported normal control data. As an index of emotional difficulties, the self-rating depressive scale (SDS) was carried out. Eighty-one school refusal students (40 males and 41 females), 11-19 years of age (14.8 +/- 2.1), were studied. Their school refusal periods ranged from one month to eight years. All students were within -15 to +20% (-0.04 +/- 8.6) of ideal body weight. BG levels were determined using a glucose oxidase reaction method. Serum hormones were measured by radioimmunoassay. BG levels at all OGTT time intervals and sigma BG were significantly higher in school refusal students than the normal control data (sigma BG: 39.5 +/- 4.4 vs 33.3 +/- 3.4 mmol/l P < 0.001). Although the insulin response was abnormally low relative to the prevailing hyperglycaemia (sigma IRI/ sigma BG: subjects vs control = 232 +/- 129 vs 375 +/- 271, P < 0.01), normal beta cell secretory ability was speculated (sigma IRI: subjects vs controls = 2805 +/- 1274 vs 2523 +/- 1219 pmol/l). This suggests a relative suppression of insulin secretion. A paradoxical increase of GH was observed in 19 students after glucose ingestion. Glucoregulatory disorders observed in school refusal students may be caused by emotional distress. Multiple factors including autonomic nervous system disorders, derangement of neuropeptides in the hypothalamus, and hormonal imbalances may also affect glucoregulatory metabolism, predisposing these students to hyperglycaemia. We speculate that the glucoregulatory system compensates for decreased blood flow to the brain by increasing blood glucose concentrations, thereby providing sufficient glucose as the primary energy source used during normal brain metabolism.

Growth hormone resistance in uremia

Growth retardation is a major complication in children with uremia. Protein restriction, calorie deficit, metabolic acidosis, renal osteodystrophy, and endocrinologic disturbances contribute to the growth failure. The effect of these factors on growth retardation can be attenuated in part by therapy with vitamin D metabolites, adequate nutrition, alkalization, and dialysis. Linear growth in children with uremia is markedly retarded despite normal or increased levels of circulating serum growth hormone. An increased growth hormone level in children with uremia is due to normal growth hormone secretion from the pituitary gland and impaired growth hormone clearance in the kidney. However, the elevated growth hormone level does not lead to a commensurate rise in serum insulin-like growth factor I (IGF-I); the serum IGF-I level is decreased or normal in relation to the degree of renal failure. This discrepancy suggests growth hormone resistance in the liver in uremia. Recent molecular techniques open a new era in studying the gene expression for growth hormone or IGF-I. There is no doubt today that growth hormone treatment has the beneficial effect of growth promotion in children with uremia, which also suggests endogenous growth hormone resistance in target organs or target cells in uremia.

Impact of long-term naltrexone treatment on growth hormone and insulin secretion in hyperandrogenic and normal obese patients

The growth hormone (GH) response to stimulation tests is impaired in obesity. Moreover, obese patients exhibit a “paradoxical” increase of GH to GH-releasing hormone (GHRH) stimulation after food ingestion; this paradoxical response is reversed by naloxone infusion. On the other hand, β-endorphin seems to exert profound effects on insulin release. Recent studies also demonstrated an impairment of GH response to several stimuli in polycystic ovary syndrome (PCOS), a condition associated with obesity, hyperinsulinism, and insulin resistance. Chronic inhibition of opioid tone by the opioid antagonist naltrexone (NTX) is able to reduce the insulin response to an oral glucose tolerance test (OGTT) in hyperinsulinemic PCOS patients. Since insulin and GH may reciprocally influence their secretion and the opioid system may have a role in the pathogenesis of hyperinsulinemia and reduced GH secretion, we have explored the involvement of these neuroendocrine mechanisms in essential obesity and in obesity associated with hyperandrogenism by a long-term treatment with an opiate antagonist. We tested seven obese patients affected by PCOS, seven matched women with essential obesity (EO), and five non-obese control subjects. All patients, in the follicular phase, underwent an OGTT (75 g) and basal hormone assay. Two days later, patients were subjected to a GHRH test. The patients then had 4 weeks of treatment with NTX 50 mg/d. Following continuation of the treatment, OGTT and GHRH tests were repeated. Insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) plasma concentrations were also determined in the basal condition before and after NTX treatment. NTX treatment reduced fasting insulin levels in patients with EO ( P < .05) and restored a normal GH response to GHRH without affecting IGF-1 and IGFBP-3 levels. In PCOS subjects, NTX reduced the insulin response to a glucose load and failed to modify the blunted GH response to GHRH. Our data suggest a significant difference in opioid system function in PCOS and EO subjects, indicating a particular form of obesity in PCOS. The opiate antagonist treatment in EO may act through the reduction of negative insulin feedback on GH secretion. In PCOS patients, the failure to improve GH secretion in obese hyperandrogenized patients may be related to a high opioidergic tone or to the inhibitory predominance of other neurotransmitters.

Immunoreactive growth hormone-releasing hormone (IR-GHRH) in the feto-placental circulation and differential effects of L-dopa, L-arginine and somatostatin-14 on the plasma levels of IR-GHRH in normal adults.

The relation of the physiological releases of growth hormone-releasing hormone (GHRH) and growth hormone (GH) into the circulation in various conditions was investigated using a sensitive and specific radioimmunoassay for plasma GHRH. The mean fasting plasma level of immunoreactive (IR)-GHRH in 72 normal adults was 10.3 +/- 0.5 (mean +/- SEM) pg/ml and there was no significant sex difference in the level. The concentrations of IR-GHRH in plasma from the umbilical artery and umbilical vein were 107.3 +/- 20.5 pg/ml and 33.6 +/- 3.8 pg/ml, respectively, and a marked arterio-venous gradient was observed in all 12 individuals examined. The plasma level of IR-GHRH in the maternal vein was significantly lower than that in the cord blood, but was similar to that in non-pregnant women. In normal adults, although there was no apparent fluctuation in the level of plasma IR-GHRH or of plasma GH during bed rest, a significant increase of plasma IR-GHRH was detected followed by, or synchronized with the surge of plasma GH after oral administration of L-dopa. In contrast, on L-arginine infusion, no proportional elevation of plasma IR-GHRH with increase in plasma GH was observed. During and after intravenous infusion of somatostatin, the circulating IR-GHRH level did not increase, but on stopping the infusion there was an immediate and marked rebound surge of GH. We conclude that 1) the elevated IR-GHRH in the cord blood plasma originates from the fetus and may have a primary role in enhancing secretion of GH which promotes growth in early human life, and 2) the participations of GHRH in the mechanisms of GH secretion seen after administrations of L-dopa, L-arginine and somatostatin are different.

Effects of single nightly injections of growth hormone—releasing hormone (GHRH 1–29) in healthy elderly men

Age-related reductions in growth hormone (GH) and insulin-like growth factor-I (IGF-I) may contribute to decreased muscle mass and strength in older persons. The relationship of this phenomenon to skeletal muscle bioenergetics has not been reported. We sought to determine whether administration of GH-releasing hormone (GHRH) would sustain increases in GH and IGF-I and improve skeletal muscle function and selected measures of body composition and metabolism. We measured GH secretion, muscle strength, muscle histology, and muscle energy metabolism by phosphorus nuclear magnetic resonance spectroscopy ( 31P-NMRS), body composition, and endocrine-metabolic functions before and after 6 weeks of treatment. Eleven healthy, ambulatory, non-obese men aged 64 to 76 years with low baseline IGF-I levels were treated at home as outpatients by nightly subcutaneous self-injections of 2 mg GHRH for 6 weeks. We measured GH levels in blood samples obtained every 20 minutes from 8:00 PM to 8:00 AM; Ann serum levels of IGF-I, IGF binding protein-3 (IGFBP-3), and GH binding protein (GHBP); muscle strength; muscle histology; the normalized phosphocreatine abundance, PCr [PCr + Pi] , and intracellular pH in forearm muscle by NMRS during both sustained and ramped exercise; body composition by dual-energy x-ray absorptiometry (DEXA); lipid levels; and glucose, insulin, and GH levels during an oral glucose tolerance test (OGTT). GHRH treatment increased mean nocturnal GH release ( P < .02), the area under the GH peak ([AUPGH] P < .006), and GH peak amplitude ( P < .05), with no change in GH pulse frequency or in levels of IGF-I, IGFBP-3, or GHBP Two of six measures of muscle strength, upright row ( P < .02) and shoulder press ( P < .04), and a test of muscle endurance, abdominal crunch ( P < .03), improved. GHRH treatment did not alter exercise-mediated changes in PCr [PCr + Pi] or intracellular pH, but decreased or abolished significant relationships between changes in PCr [PCr + Pi] or pH and indices of muscle strength. GHRH treatment did not change weight, body mass index, waist to hip ratio, DEXA measures of muscle and fat, muscle histology, glucose, insulin, or GH responses to OGTT, or lipids. No significant adverse effects were observed. These data suggest that single nightly doses of GHRH are less effective than multiple daily doses of GHRH in eliciting GH- and/or IGF-I—mediated effects. GHRH treatment may increase muscle strength, and it alters baseline relationships between muscle strength and muscle bioenergetics in a manner consistent with a reduced need for anaerobic metabolism during exercise. Thus, an optimized regimen of GHRH administration might attenuate some of the effects of aging on skeletal muscle function in older persons.

Arginine supplementation increases weight gain, depresses antibody production, and alters circulating leukocyte profiles in preruminant calves without affecting plasma growth hormone concentrations.

The hypothesis that dietary L-arginine (L-Arg) supplementation would increase growth hormone (GH) secretion and antibody production in preruminant calves was tested. Sixteen newborn calves were randomly assigned to either Arg+ or Arg- treatment groups. Both groups were fed a single dose of Colostrx within 6 h after birth followed by milk replacer twice daily until weaning. Beginning with the Colostrx feeding, calves in the Arg+ group were supplemented with L-arginine at 500 mg kg x BW(-1) x d(-1), and the Arg- group received equivalent, but unsupplemented, diets. All calves were immunized against keyhole limpet hemocyanin (KLH) on d 4 and received a booster vaccination on d 14. The Arg+ treatment increased (P < .05) plasma L-Arg and urea concentrations an average of 2.8-fold and 26%, respectively, during the 4-wk supplementation period. Average daily gain (ADG) of Arg+ calves was increased (P < .10) during wk 1, 3, and 5 of life. The Arg+ treatment depressed (P < .05) total and KLH-specific IgG concentrations in plasma and caused a decrease (P < .01) in circulating leukocyte numbers. Differential counts revealed that the decrease in circulating leukocyte numbers was due to decreases in absolute numbers of lymphocytes, monocytes, and neutrophils. The Arg+ diet did not affect mean plasma GH concentrations during the first 3 wk of life, but GH mean concentrations were decreased (P < .01) during wk 4 due to depressed (P < .10) pulse amplitudes. The decrease in GH mean concentrations during wk 4 was paralleled by lower (P < .10) plasma IGF binding protein-3 concentrations. These data show that supplementary L-Arg does not increase plasma GH concentrations, but it increases ADG, depresses KLH antibody production, and alters circulating leukocyte populations in preruminant calves.

Optimizing growth hormone therapy during puberty.

During puberty, growth hormone (GH)-deficient children may experience difficulties achieving an appropriate pubertal growth spurt. We review the complex hormonal interactions which occur during puberty. At least two therapeutic strategies have been developed to optimize GH therapy during puberty. In the first strategy, the GH dose administered per kilogram of body weight is increased during puberty, in an attempt to mimic the physiological increase of GH which occurs during puberty. In the second strategy, luteinizing hormone-releasing hormone (LHRH) analogs are administered concomitantly with GH with the aim of delaying epiphyseal fusion. The efficacy of these strategies to increase final height has not previously been clearly demonstrated.

Defective 5-HT 1-receptor-mediated neurotransmission in the control of growth hormone secretion in Parkinson's disease.

In order to gain a better insight in the serotonergic disorder affecting the parkinsonian brain, the growth hormone (GH) response to the 5-HT 1 serotonergic receptor agonist sumatriptan was tested. Sumatriptan was injected subcutaneously in 10 de novo parkinsonian patients (aged 58-69 years) and in 9 age-matched normal controls. On different occasions, subjects were also tested with GH-releasing hormone (GH-RH; 1 micrograms/kg body weight in an intravenous bolus) and L-arginine (30 g in 50 ml normal saline over 30 min), which releases GH from somatostatin inhibition, to determine whether GH secretion in response to alternate secretagogues is preserved in Parkinson's disease. In addition, a control test with the administration of normal saline instead of drug treatments was performed. Plasma GH levels were recorded over 2 h in all tests. Placebo administration did not change plasma GH levels in any subject. Similar GH responses were observed in normal controls and parkinsonian patients when GH-RH or arginine were administered. A significant GH increase was observed in normal controls after sumatriptan injection; in contrast, GH secretion was not modified by sumatriptan administration in parkinsonian patients. These data show that Parkinson's disease is associated with an impairment in the 5-HT1-receptor-mediated serotonergic transmission in the control of GH secretion, suggesting that this specific defect might alter other serotonergic-mediated mechanisms in the parkinsonian brain.