Chronic Administration Of Growth Hormone Research Articles

Regenerative Effect of Growth Hormone (GH) in the Retina after Kainic Acid Excitotoxic Damage.

In addition to its role as an endocrine messenger, growth hormone (GH) also acts as a neurotrophic factor in the central nervous system (CNS), whose effects are involved in neuroprotection, axonal growth, and synaptogenic modulation. An increasing amount of clinical evidence shows a beneficial effect of GH treatment in patients with brain trauma, stroke, spinal cord injury, impaired cognitive function, and neurodegenerative processes. In response to injury, Müller cells transdifferentiate into neural progenitors and proliferate, which constitutes an early regenerative process in the chicken retina. In this work, we studied the long-term protective effect of GH after causing severe excitotoxic damage in the retina. Thus, an acute neural injury was induced via the intravitreal injection of kainic acid (KA, 20 µg), which was followed by chronic administration of GH (10 injections [300 ng] over 21 days). Damage provoked a severe disruption of several retinal layers. However, in KA-damaged retinas treated with GH, we observed a significant restoration of the inner plexiform layer (IPL, 2.4-fold) and inner nuclear layer (INL, 1.5-fold) thickness and a general improvement of the retinal structure. In addition, we also observed an increase in the expression of several genes involved in important regenerative pathways, including: synaptogenic markers (DLG1, NRXN1, GAP43); glutamate receptor subunits (NR1 and GRIK4); pro-survival factors (BDNF, Bcl-2 and TNF-R2); and Notch signaling proteins (Notch1 and Hes5). Interestingly, Müller cell transdifferentiation markers (Sox2 and FGF2) were upregulated by this long-term chronic GH treatment. These results are consistent with a significant increase in the number of BrdU-positive cells observed in the KA-damaged retina, which was induced by GH administration. Our data suggest that GH is able to facilitate the early proliferative response of the injured retina and enhance the regeneration of neurite interconnections.

SUN-253 Effects of Growth Hormone Stimulation on the Immunologic Cellular Landscape in Pediatric Patients

Background: Multiple complex interactions exist between growth hormone (GH)-Insulin like growth factor-1 axis and the immune system. We and others have demonstrated GH receptors on the cell surface of peripheral blood mononuclear cells, human IM-9 cultured lymphocytes, thymus, spleen and lymph nodes. Administration of GH to GH deficient (GHD) children has shown a transient decrease in percent B cells and T cell percentages, interleukin-2 receptor levels and lymphocyte mitogenic stimulation response. Data about acute effects of GH on the immune system are lacking. Aim: The aim of this study was to evaluate the acute effect of endogenous GH on the cellular landscape of the immune system. Methods: A prospective study was conducted in pediatric patients being evaluated for short stature who underwent a standard 3-hour growth hormone stimulation test using arginine and glucagon. Exclusion criteria included genetic syndromes, renal failure, recent immunosuppressant or steroid use and small for gestational age. Blood samples for immunologic markers, that included complete blood count (CBC) and time of flight mass flow cytometry (CyTOF), were collected at the beginning (T0) and end (T3) of the test. Differences in patients by time point (T0 and T3) and by GH response to stimulation (growth hormone sufficient {GHS} versus GHD) were calculated using a two-way ANOVA test with repeated measures over time, considering the interaction between time point and GH status. Results: Fifty-four patients (39 boys, 15 girls) aged 5-18 years, were enrolled in the study. Twenty-two participants had peak GH level <10 ng/ml (GHD). Both GHD and GHS groups were not statistically different in age, gender, pubertal status, height standard deviations (SDs), weight SDs, BMI and IGF-1 SD values, but did differ in growth velocity. Absolute lymphocyte count, lymphocyte percentage, absolute eosinophil count, absolute monocyte count and platelet count demonstrated significant (p<0.05) decrease from T0 to T3. Consistent with CBC analysis, CyTOF analysis showed a decrease (p<0.05) from T0 to T3 in percentages of B cells, monocytes, plasmacytoid dendritic cells, T helper cells and a subset of cytotoxic T cells with low CD57 expression. These results are consistent with previous reports of chronic GH administration. Total white blood cell (WBC) count, absolute neutrophil count and neutrophil percentage demonstrated increase (P<0.05) from T0 to T3, as did granulocyte percentage by CyTOF. Overall, no significant differences were found between CBC or CyTOF measurements and GH status at either time point (T0 and T3). Conclusions: The study provides the first high-resolution map of acute changes in the immune system with GH stimulation. CBC and CyTOF analyses showed significant changes, consistent with previous studies during chronic GH administration. No significant differences were observed between the GHD and GHS groups.

Effect of chronic administration of growth hormone on JAK2-STAT5 signaling pathway in the liver

Effect of chronic administration of growth hormone on JAK2-STAT5 signaling pathway in the liver

Influence of aging and growth hormone on different members of the NFkB family and IkB expression in the heart from a murine model of senescence-accelerated aging

Inflammation is related to several pathological processes. The aim of this study was to investigate the protein expression of the different subunits of the nuclear factor Kappa b (NFkBp65, p50, p105, p52, p100) and the protein expressions of IkB beta and alpha in the hearts from a murine model of accelerated aging (SAM model) by Western blot. In addition, the translocation of some isoforms of NFkB from cytosol to nuclei (NFkBp65, p50, p52) and ATP level content was studied. In addition we investigated the effect of the chronic administration of growth hormone (GH) on these age-related parameters. SAMP8 and SAMR1 mice of 2 and 10months of age were used (n=30). Animals were divided into five experimental groups: 2 old untreated (SAMP8/SAMR1), 2 young control (SAMP8/SAMR1) and one GH treated-old groups (SAMP8). Age-related changes were found in the studied parameters. We were able to see decreases of ATP level contents and the translocation of the nuclear factor kappa B p50, p52 and p65 from cytosol to nuclei in old SAMP8 mice together with a decrease of IKB proteins. However p100 and p105 did not show differences with aging. No significant changes were recorded in SAMR1 animals. GH treatment showed beneficial effects in old SAMP8 mice inducing an increase in ATP levels and inhibiting the translocation of some NFkB subunits such as p52. Our results supported the relation of NFkB activation with enhanced apoptosis and pro-inflammatory status in old SAMP8 mice and suggested a selective beneficial effect of the GH treatment, which was able to partially reduce the incidence of some deleterious changes in the heart of those mice.

Modification of the Metabolomic Profile Induced by Chronic Growth Hormone Administration in a Doping Model

IntroductionHorses performance can be enhanced via growth hormone (GH) doping. The detection time for GH in blood is too short to allow detection during competition. GH not only affects the proteosynthesis in cells and tissues but can also cause long term metabolic variations. This study aimed to show the metabolomic modifications occurring after three months of GH treatment.MethodsThe study was performed on 20 Welsh ponies. 10 were injected with REPORCIN TM, an approved recombinant GH (30 mg.kg−1 per day) for 3 months and the other 10 comprised the control group. Blood samples were collected before GH treatment (T0), then 3 months later (T3). The NMR spectra acquired on the 40 serum samples were classified according to the factors (season, GH treatment) using the supervised multivariate orthogonal projection on latent structure (OPLS) method. A first OPLS model was computed with the control ponies (T0‐T3). The predictive component of this model was subtracted from the whole data (treated, controls at T0 and T3) to only retain the GH‐dependent variations.ResultsBefore filtering seasonal effects, glucose, lipids and phospholipids were metabolites discriminating between T0 and T3 samples. After removing the seasonal effect, the OPLS model revealed the effect of GH treatment on protein metabolism through the modification of aromatic amino acids and branched chain amino acids. The variations of other metabolites (glycoproteins and lactate) were enhanced.ConclusionsThis study showed that chronic GH injection induced systemic metabolism modifications that can be detected using the NMR metabolomic method without neglecting the misleading effect of season.Ethical Animal ResearchStudies approved by “Comité regional d′éthique pour l′expérimentation animale Centre Limousin” Saisine N° CL2008_015. Sources of funding: French Agency against Doping (AFLD). Competing interests: none.

Cardiological aging in SAM model: effect of chronic treatment with growth hormone

The purpose of this study was to investigate the effect of aging on different parameters related to inflammation, oxidative stress and apoptosis in hearts from two types of male mice models: senescence-accelerated mice (SAM-P8) and senescence-accelerated-resistant (SAM-R1), and the influence of chronic administration of Growth Hormone (GH) on old SAM-P8 mice. Forty male mice were used. Animals were divided into five experimental groups: two 10 month old untreated groups (SAM-P8/SAM-R1), two 2 month old young groups (SAM-P8/SAM-R1) and one 10 month old group (SAM-P8) treated with GH for 30 days. The expression of tumor necrosis factor-alpha, interleukin 1, interleukin 10, heme oxygenases 1 and 2, endothelial and inducible nitric oxide synthases, NFkB, Bad, Bax and Bcl-2 were determined by real-time reverse transcription polymerase chain reaction (RT-PCR). Results were submitted to a two way ANOVA statistical evaluation using the Statgraphics program. Inflammation, as well as, oxidative stress and apoptosis markers were increased in the heart of old SAM-P8 males, as compared to young controls and this situation was not observed in the old SAM-R1 mice. Exogenous GH administration reverted the effect of aging in the described parameters of old SAM-P8 mice. Our results suggest that inflammation, apoptosis and oxidative stress could play an important role in the observed cardiovascular alterations related to aging of SAM-P8 mice and that GH may play a potential protective effect on the cardiovascular system of these animals.

Growth Hormone Enhances Excitatory Synaptic Transmission in Area CA1 of Rat Hippocampus

The hippocampus produces growth hormone (GH) and contains GH receptors, suggesting a potential role for GH signaling in the regulation of hippocampal function. In agreement with this possibility, previous investigations have found altered hippocampal function and hippocampal-dependent learning and memory after chronic GH administration or deficiency. In this study we applied GH to in vitro rat hippocampal brain slices, to determine whether GH has short-term effects on hippocampal function in addition to previously documented chronic effects. We found that GH enhanced both AMPA- and NMDA-receptor-mediated excitatory postsynaptic potentials (EPSPs) in hippocampal area CA1, but did not alter GABA(A)-receptor-mediated inhibitory synaptic transmission. GH enhancement of excitatory synaptic transmission was gradual, requiring 60-70 min to reach maximum, and occurred without any change in paired-pulse facilitation, suggesting a possible postsynaptic site of action. In CA1 pyramidal neurons, GH enhancement of EPSPs was correlated with significant hyperpolarization and decreased input resistance. GH enhancement of EPSPs required Janus kinase 2 (JAK2), phosphatidylinositol-3 (PI3) kinase, mitogen-activated protein (MAP) kinase kinase (MEK), and synthesis of new proteins. Although PI3 kinase and MEK were required for initiation of GH effects on excitatory synaptic transmission, they were not required for maintained enhancement of EPSPs. GH treatment and tetanus-induced long-term potentiation were mutually occluding, suggesting a common mechanism or mechanisms in both forms of synaptic enhancement. Our results demonstrate that GH has powerful short-term effects on hippocampal function, and extend the timescale for potential roles of GH in regulating hippocampal function and hippocampal-dependent behaviors.

Growth hormone, vascular reactivity, and heart failure

The growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis plays a relevant role in the regulation of vascular growth and function, as demonstrated by the data obtained in GH-deficient patients, in whom endothelial function is severely impaired. The treatment of these patients with GH is able to restore a normal endothelial function. Patients affected by congestive heart failure (CHF) are also characterized by endothelial dysfunction. Such a defect represents a key factor in the progression of the disease. Therefore, the possibility of using GH to correct endothelial dysfunction in patients with CHF has been proposed. Experimental data have demonstrated that chronic GH administration improves endothelial dysfunction in CHF patients. On the other hand, GH administration in normal healthy volunteers has been shown to positively affect endothelial function after a few hours of infusion, suggesting that GH can rapidly modify vascular functions. The mechanisms involved in the regulation of vascular function by GH are at the moment not completely clear. However, the positive effect of GH on endothelial dysfunction may be linked to a direct effect of GH on endothelial cells, an IGF-I-mediated effect, an increase in cardiac output, and a decrease of cytokine activation.

Endotoxin Enhances Liver Alcohol Dehydrogenase by Action through Upstream Stimulatory Factor but Not by Nuclear Factor-κB

Liver alcohol dehydrogenase (ADH) is increased by physiological stress and by chronic administration of growth hormone (GH). Endotoxin plays a role in the pathogenesis of alcoholic liver disease. The effect of lipopolysaccharide (LPS), the endotoxin component of Gram-negative bacteria, was determined on liver ADH. LPS given daily to rats for 3 days increased ADH mRNA, ADH protein, and ADH activity. Nuclear factor-kappaB (NF-kappaB) in the liver nuclear extracts bound to an oligonucleotide specifying region -226 to -194 of the ADH promoter, whereas upstream stimulatory factor (USF) was shown previously to bind to a more proximal site. LPS increased NF-kappaB and USF binding to the ADH promoter. The NF-kappaB (p65) and NF-kappaB (p50) expression vectors inhibited the transfected ADH promoter activity, which contrasts with the previously demonstrated stimulation by an USF expression vector. The binding activities of STAT5b and of C/EBPbeta, which mediate the effect of GH on ADH, were not changed or decreased, respectively, by LPS, indicating that GH plays no intermediary role in the effect of LPS. This study shows that LPS increases ADH and that this effect is mediated by increased binding of USF to the ADH promoter and not by NF-kappaB, which has an inhibitory action.

Echocardiographic assessment of cardiac morphology and function in mutant dwarf rats.

Although the mutant dwarf rat has been proposed as a model of growth hormone (GH) deficiency, few studies have addressed its cardiovascular abnormalities. Therefore, the aim of the present study was to investigate cardiac structure and function in mutant dwarf rats in vivo before and after chronic GH administration, by means of transthoracic Doppler echocardiography. To this purpose, forty 90-day-old female dwarf rats were randomized to receive either GH treatment or placebo. Twenty age-and sex-matched Lewis rats (200-250 g) served as the control group. All rats underwent echocardiograms before receiving any drug and after 3 weeks of therapy. Echocardiographically detected left ventricular mass indexed to tibial length was reduced by 41% in dwarf rats compared to the control group. Such relative cardiac atrophy was also evident at the myocyte level, and was fully reversible after GH therapy. In contrast to the control group, dwarf rats also showed a reduction of left ventricular diastolic volumes normalized to tibial length and impaired cardiac performance as suggested by the reduction of cardiac index, abnormal stress-shortening relations, and a significant elevation of total peripheral vascular resistance. All these abnormalities were reversible upon GH therapy for 3 weeks. In conclusion, GH plays an important role in maintaining a normal cardiac structure and function. Since the observed changes are similar to those seen in GH-deficient men, the mutant dwarf rat represents a faithful animal model of GH deficiency.

Serum Leptin Response to the Acute and Chronic Administration of Growth Hormone (GH) to Elderly Subjects with GH Deficiency

Serum Leptin Response to the Acute and Chronic Administration of Growth Hormone (GH) to Elderly Subjects with GH Deficiency

Serum leptin response to the acute and chronic administration of growth hormone (GH) to elderly subjects with GH deficiency.

In human studies, the principal determinant of serum leptin concentrations is fat mass (FM), but lean mass (LM) also has a significant negative influence. GH treatment in GH deficiency (GHD) alters body composition, increasing LM and decreasing FM, and thus would be expected to alter leptin concentrations. We have therefore examined the acute and chronic effects of GH on serum leptin in 12 elderly GHD subjects (ages 62-85 yr; 3 women and 9 men). FM (kilograms) and LM (kilograms) were determined by dual energy x-ray absortiometry. Leptin, insulin, insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 were measured by specific immunoassays. Leptin, insulin, and IGFBP-1 concentrations were log10 transformed, and data were expressed as the geometric mean (-1, +1 tolerance factor). All other data are presented as the mean +/- SD. In the acute study, patients received a single bolus dose of GH (0.1 mg/kg BW) at time zero, with blood samples drawn at 0, 12, 24, 48, and 72 h and 1 and 2 weeks. There was a significant rise in leptin, insulin, and IGF-I at a median time of 24 h, followed by a significant fall, and nadir concentrations were reached at a median time of 1.5 weeks (leptin) or 2 weeks (insulin and IGF-I). IGFBP-3 concentrations were also significantly increased, but peak concentrations were not achieved until 48 h. IGF-II, IGFBP-1, and IGFBP-2 exhibited transient decreases before returning to baseline levels. There was no relationship between increased leptin concentrations and either insulin or IGF-I concentrations. In the chronic study, patients received daily GH treatment at doses of 0.17, 0.33, and 0.5 mg/day, each for 3 months (total time on GH, 9 months), and were then followed off GH for a further 3 months. Dual energy x-ray absortiometry was undertaken at 0, 3, 6, 9, and 12 months, and blood samples were drawn at these time points. Over 9 months on GH there was a significant fall in FM and a significant rise in LM, but no change in leptin. There were also significant increments in insulin, IGF-I, and IGFBP-3, whereas IGF-II, IGFBP-1, and IGFBP-2 did not change over 9 months of GH treatment. After 3 months off GH, there was a significant rise in FM and leptin. High dose single bolus GH led to an increase in serum leptin within 24 h apparently independent of changes in insulin or IGF-I. Despite the changes in body composition during chronic GH treatment, there was no change in leptin. However, discontinuation of GH led to a rapid reversal of the favorable body composition and a rise in serum leptin.

Insulin-like growth factor-I and growth hormone administration in intestinal ischemia shock in the rat.

The effect of exogenous insulin-like growth factor (IGF)-I and growth hormone (GH) was examined in a rat model of intestinal ischemia-reperfusion (I/R). Animals were anesthetized, vascular catheters were placed, and intestinal ischemia was induced for 60 min. Thereafter, the intestine was reperfused, and rats received a primed, constant infusion of either IGF-I or GH (500 microg/rat + 500 microg/day) for the remainder of the study; control rats received an equal volume of vehicle. The plasma IGF-I concentration gradually declined after I/R in the vehicle-shock group and was reduced 30% at 48 h. GH infusion completely prevented this reduction, whereas the effect of IGF-I was intermediate. The IGF-I content in liver was increased by IGF-I (78%) and further enhanced in the GH-treated group (140%). Comparable increases were seen for the abundance of IGF-I mRNA in liver in these two treatment groups, compared to the vehicle control. In contrast, while both IGF-I and GH elevated the IGF-I content in skeletal muscle similarly (80%), no increase in IGF-I mRNA expression was observed in this tissue. Neither treatment altered the IGF-I content in small intestine. At the time tissues were sampled (48 h), the plasma concentration of glucose and corticosterone was not different among the three groups. However, plasma insulin was reduced 50% in the IGF-I-infused animals, compared to values in either the shock-GH or shock-vehicle group. These data demonstrate that chronic administration of GH and, to a lesser extent, IGF-I, after intestinal I/R maintains levels of IGF-I in the blood, liver, and muscle. Thus, adjunct treatment with these anabolic agents may help blunt the increased catabolism observed in individuals following intestinal I/R.

Chronic administration of growth hormone (GH) to adult chickens exerts marked effects on circulating concentrations of insulin-like growth factor-I (IGF-I), IGF binding proteins, hepatic GH regulated gene I, and hepatic GH receptor mRNA.

In young birds, growth hormone (GH) administration has been found to have only a small or even no effect on circulating concentrations of insulin-like growth factor-I (IGF-I). This is in obvious contrast to the situation in mammals. The present study examines the effect of continuous administration of GH in adult male chickens. Plasma concentrations of IGF-I were markedly elevated (2.5-3.0-fold, p < 0.001) in GH-treated chickens. There were also some transient increases in the circulating levels of IGF binding proteins. Adult chickens showed other manifestations of increased responsiveness to GH, including elevated hepatic expression of GH-regulated gene-I (mRNA) with GH treatment (p < 0.05), and a tendency (p < 0.08) for decreased GH-receptor mRNA. In contrast to the changes in circulating concentrations of GH and IGF-I with GH treatment, no changes in plasma concentrations of thyroid hormones, reproductive hormones, glucose, or nonesterified fatty acids were evident.

Lipolytic and diabetogenic effects of native and biosynthetic growth hormone in the chicken: A re-evaluation

1. 1. There is controversy as to whether growth hormone (GH) is lipolytic and/or diabetogenic in vivo in chickens. The ability of GH to influence circulating concentrations of free fatty acids was examined in anaesthetized (suppressing endogenous GH secretion) adult and young chickens using three preparations of GH. 2. 2. Plasma concentrations of free fatty acids were increased following the intravenous injection of native bovine GH (50 μg/kg to either young or adult chickens), recombinant chicken GH (American Cyanamid) (50 μg/kg to adult chickens) and recombinant chicken GH (Amgen) (50μg/kg to young chickens). 3. 3. Similarly, infusion of recombinant chicken GH was accompanied by a gradual increase ( P < 0.05, 90 min following start of infusion) in plasma concentrations of free fatty acids in both anaesthetized hypophysectomized and sham operated young chickens. 4. 4. These data support an acute lipolytic role for GH in the chicken. 5. 5. The injection of neither bovine nor chicken GH had any consistent effect on circulating concentrations of glucose. Moreover, if GH was administered in the presence of glucose, GH had no effect on plasma concentrations of glucose. 6. 6. Further evidence for a lack of a diabetogenic role for GH comes from the inability of chronic administration of GH to influence the decline in plasma concentrations of glucose following challenge with the insulin secretagogue, tolabutamide.

Chronic Growth Hormone Administration Does Not Suppress Endogenous Growth Hormone Secretion in Patients with Neurosecretory Growth Hormone Dysfunction

Short children who respond normally to growth hormone (GH) stimulation, but have a subnormal spontaneous secretion of GH (neurosecretory GH dysfunction, NSD) are treated with exogenous GH which might suppress their endogenous GH secretion. The effect of chronic administration of GH (8-24 months) on plasma GH responses to GHRH, clonidine and spontaneous GH secretion were studied in 17 NSD patients. The diagnosis of NSD was based on a normal GH response to clonidine (greater than 10 micrograms/l) and an integrated concentration of (IC-GH) GH less than 3.2 micrograms/l. The GH dose used in this study was 0.25 IU/kg three times a week in 10 patients and 0.05 IU/kg daily in 7 patients. Insulin-like growth factor I levels (nmol) increased significantly on therapy from 9.3 +/- 3.8 to 24.4 +/- 22.4 (p less than 0.001). The GH response (microgram/l) to GHRH was 20.4 +/- 5.5 before treatment and 22.4 +/- 6.2 on GH. Peak GH after clonidine was 22.4 +/- 8.9 and 22.8 +/- 8.1, respectively. There was no significant decrease in the number of GH spontaneous peaks (1.8 +/- 0.7 vs. 2.0 +/- 0.7, respectively) or in the area under the curve. A subcutaneous GH bolus of 0.25 IU/kg in 4 patients resulted in a GH peak of 55-82 micrograms/l at 3-5 h and a gradual return to basal levels at 15-20 h after GH administration. The first spontaneous GH peak appeared 26-28 h after GH injection, peak amplitude was 10-15 micrograms/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth Acceleration of Seawater-Adapted Female Chinook Salmon Oncorhynchus tshawytscha by Constant Infusion of Recombinant Bovine Growth-Hormone Under Ambient Summer Conditions

Seawater-adapted female chinook salmon (Oncorhynchus tshawytscha) in their second summer were treated with one of three doses of recombinant bovine growth-hormone (rbGH) administered in a continuous fashion by osmotic pump for approximately five weeks. Untreated fish, sham-treated fish and fish treated with the low dose of hormone (0.003 μg/g bwt/day) did not differ significantly in their growth performance over the 10 week course of the experiment. By the end of the treatment period (week 6) the mean increases in fork length and weight for these groups were 7.6% and 38.9%, respectively. A dose-dependent enhancement of growth was observed for the fish treated with the mid (0.016 μg/g bwt/day) and high (0.078 μg/g bwt/day) doses of hormone. After 6 weeks, the fish given the mid dose of rbGH had gained 9.6% in fork length and 45.3% in weight, while the fish treated with the high dose of rbGH had gained 13.9% in fork length and 52.9% in weight. A significant increase in specific growth rate was observed for these latter two groups during the treatment period while condition factor declined in response to the high dose of rbGH. This experiment indicates that chronic administration of growth-hormone to chinook salmon can result in a dose dependent elevation of growth rate. Results are discussed in relation to previous attempts to accelerate the growth of Pacific salmon with growth-hormone and the potential for using recombinant growth-hormone to improve the production characteristics of salmon being cultured in seawater.

Failure of chronic administration of growth hormone to affect blood pressure, vascular reactivity and sodium metabolism in normal rats.

To examine the effects of exogenous growth hormone on the cardiovascular system and sodium metabolism, ovine growth hormone was given daily to female rats for 5 weeks. Growth hormone resulted in a significant increase in body mass compared with controls. However, blood pressure in the treated rats was not significantly different from that in controls. Following treatment, the baseline resistances and pressor responses of the isolated mesenteric beds did not differ between the two groups. In addition, exchangeable sodium, erythrocytic intracellular sodium and transmembrane sodium efflux rate constants were not altered significantly by growth hormone treatment. The failure to observe cardiovascular or sodium effects of growth hormone despite significant potentiation of growth is, at present, unexplained.

The effects of acute and chronic growth hormone (GH) administration on GH secretion in patients with idiopathic GH deficiency.

The effect of acute and chronic administration of GH on plasma GH responses to GHRH were studied in patients with idiopathic GH deficiency (GHD). Nine untreated GHD patients, 1 untreated patient with postoperative craniopharyngioma, and 7 normal short children were given synthetic human GHRH-44 (100 micrograms, iv) injection before and 2 days after being given a single dose of 4 IU biosynthetic methionyl human GH (mGH), im. Twelve GHD patients, who had been treated with 0.31-0.48 IU/kg.week pituitary-derived hGH (pdGH), im, for 8-79 months, were given GHRH 2 and 14 days after a final injection of 4 IU pdGH. Three other GHD patients were given GHRH before and after 2 yr of pdGH therapy (0.35-0.39 IU/kg.week). The GHRH-induced GH response (max delta GH) was significantly inhibited after mGH administration in the 9 untreated GHD patients [2.7 +/- 0.3 (+/- SE) vs. 4.7 +/- 0.6 micrograms/L; P less than 0.01]. The patient with secondary GH deficiency also had a marked reduction in her peak plasma GH value after mGH administration (from 32.0 to 11.7 micrograms/L). Similarly, the mean max delta GH response in the 7 normal short children was significantly inhibited by prior mGH injection (max delta GH, 12.7 +/- 2.0 vs. 28.8 +/- 4.8 micrograms/L; P less than 0.01). In the 12 treated GHD patients the GHRH-induced GH response on the 2nd day after discontinuation of pdGH therapy was significantly lower than that on the 14th day (max delta GH, 3.4 +/- 1.2 vs. 6.9 +/- 1.6 micrograms/L; P less than 0.02). In the 3 GHD patients who were studied before and after 2 yrs of pdGH therapy, the plasma GH responses were similar. In each group, plasma somatomedin-C levels on the second day after GH administration were slightly but not significantly higher than those before or 14 days after the administration. The GH responses to GHRH given on 2 occasions at 7- to 14-day intervals in individuals not receiving GH were similar in both 9 normal children and 10 GHD patients. These results indicate that acute GH administration inhibits somatotroph function in GHD patients, but chronic GH therapy does not cause irreversible damage to the somatotrophs. The acute inhibition of GHRH-induced GH release after GH administration is more likely due to direct and indirect pituitary inhibition by somatomedin-C and/or somatostatin than decreased GHRH secretion.

Endocrine Regulation of Fetal and Postnatal Meat Animal Growth

Evidence is discussed which indicates that nutrient partitioning between muscle and adipose tissue can be altered by growth hormone administration in meat animals. In the limited number of studies conducted with meat animals, growth rate, feed efficiency and carcass composition were improved by growth hormone administration. When insulin was administered to normally growing swine no improvement in growth performance was observed. The mechanisms by which growth hormone affects growth performance are not clear but considerable data from rodent studies exist to indicate that many of the growth promoting effects of this hormone are due to somatomedins. However, few data are available for meat animals to indicate whether the growth promoting effects of growth hormone are mediated by somatomedins. Knowledge about the mechanisms that regulate growth hormone synthesis, secretion and biological action is accumulating. It is apparent that growth hormone administration induces an insulin-resistant state in rodents and meat animals. It is not clear whether chronic growth hormone administration in meat animals induces a growth hormone resistant state. Based on the available information, manipulation of systemic hormone concentrations and(or) tissue sensitivity to hormones involved in growth and differentiation may result in means to manipulate fetal and postnatal growth and development.