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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Growth hormone (GH) increases glomerular filtration rate and renal plasma flow and decreases renal vascular resistance. Sustained GH-induced hyperfiltration might be undesirable in children with chronic renal failure (CRF) who are receiving recombinant human GH (rhGH) therapy. 2. In order to determine the effect of CRF on vascular reactivity and the modifications induced by rhGH administration, two endothelium-dependent effects, acetylcholine relaxation and decrease of contractile response to noradrenaline, were studied in aorta segments of various groups of male Sprague-Dawley rats: CRF rats (CRF, n = 8) with serum urea nitrogen (SUN) 68 +/- 16 mg dl-1 (mean +/- SEM), CRF rats treated with intraperitoneal rhGH at 10 IU kg-1 day-1 for 13 days (CRFGH, n = 6, SUN = 88 +/- 15 mg dl-1), sham operated rats (SHAM, n = 8, SUN: 21 +/- 1 mg dl-1) and control rats (CONTROL, n = 8, SUN 20 +/- 1 mg dl-1), housed in identical conditions but without undergoing surgical intervention or manipulation. CRF was induced by 5/6 two stage nephrectomy. 3. Rats were sacrificed and a segment of thoracic aorta was immediately removed, cut into spirals, and suspended in organ baths according to standard procedures. First, dose-response curves to noradrenaline and acetylcholine relaxation, in strips previously exposed to noradrenaline, were determined. Then, the endothelium was removed and both dose-response curves were repeated. Acetylcholine induced a greater relaxation, P < 0.05, in the aorta of CONTROL rats (82.6 +/- 6.1%) as compared with SHAM (60.3 +/- 4.7%), CRF (60.0 +/- 6.8%) and CRFGH (54.8 +/- 8.2%) rats. 4. Endothelium removal only caused a greater contractile response to noradrenaline (10(-9) and 3 x 10(-9)M) in the CONTROL group, P < 0.05. 5. No differences to acetylcholine and noradrenaline responses were found among the SHAM, CRF and CRFGH groups. 6. These results suggest that the endothelium-dependent vascular reactivity was modified by the experimental protocol to induce chronic renal failure but no further changes resulted from uraemia and rhGH treatment.
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PMID:Chronic renal failure and human growth hormone treatment do not modify endothelium-dependent reactions in the rat aorta in vitro. 884 70

We have examined whether alterations in the growth hormone/insulin-like growth factor-1 axis play a role in the pathogenesis of psoriasis. Serum, urine, full skin biopsies, and suction blister roofs were obtained from patients with psoriasis and from healthy controls. Serum concentrations of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 were measured by radioimmunoassay. Growth hormone-binding protein was measured by ligand-mediated immunofunctional assay. Growth hormone concentration in urine was measured by an immunometric assay, and growth hormone receptor-gene expression was measured by RNase protection assay or by quantitative reverse transcriptase polymerase chain reaction in total RNA isolated from epidermal suction blister roofs. Serum concentrations of insulin-like growth factor-1 (249 +/- 12 micrograms per liter, mean +/- SEM, n = 42, and 277 +/- 21 micrograms per liter, n = 9, for psoriatic patients and controls, respectively), insulin-like growth factor binding protein-3 (3.1 +/- 0.08 mg per liter, n = 42, and 3.3 +/- 0.22 mg per liter, n = 9), growth hormone-binding protein (344 +/- 65 pmol per liter, n = 10, and 311 +/- 83 pmol per liter, n = 9), urinary growth hormone excretion during 24 h (12.8 +/- 2.7 microIU per 24 h, n = 12, and 12.3 +/- 1.6 microIU per 24 h, n = 9), and epidermal growth hormone receptor gene expression [32 +/- 12 x 10(3) mRNA transcripts per microgram total RNA (involved skin), n = 11, and 47 +/- 14 x 10(3) mRNA transcripts per microgram total RNA, n = 9] were similar in patients and controls. For insulin-like growth factor-1 and insulin-like growth factor binding protein-3 the values in psoriatic patients were also similar to those in larger control groups, n = 195 and n = 400, respectively. In addition, we found no evidence of local expression of growth hormone or prolactin in full skin punch biopsies from psoriatic involved skin by reverse transcriptase polymerase chain reaction. In conclusion, our results suggest that alterations in the growth hormone/ insulin-like growth factor-1 axis do not play a major role in the pathogenesis of psoriasis.
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PMID:No evidence for involvement of the growth hormone/insulin-like growth factor-1 axis in psoriasis. 934 96

Growth hormone (GH) has been suggested as a therapeutic tool for the treatment of osteopenia. To assess the differential influence of growth hormone on cortical and trabecular bone, bone mineral densities (BMD) of the ultradistal radius were determined in 18 men and 19 women with clinically and biochemically confirmed acromegaly using peripheral computed tomography and a specialized scanner (Stratec XCT 900). The results were expressed in equivalents to hydroxyl-apatite (mg/ccm) and compared with the BMD of healthy controls (17 men, 34 women). Cortical bone mineral density was significantly higher in acromegalic women (295.2 +/- 18.4, X +/- SEM) and men (339.4 +/- 21.2) compared to healthy women (243.0 +/- 12.8) and men (272.2 +/- 15.9). In contrast, trabecular BMD did not differ between acromegalic patients (men: 161.0 +/- 16.1; women: 116.5 +/- 10.5) and controls (men: 158.0 +/- 12.2; women: 134.1 +/- 6.3). Acromegalic women showed a significant correlation between insulin-like growth factor (IGF-I) expression and cortical BMD, whereas in acromegalic men GH levels correlated significantly with cortical BMD. Greatly increased serum osteocalcin levels in both, acromegalic men (15.5 +/- 3.3 ng/ml) and women (12.9 +/- 1.8) compared to controls (men: 6.7 +/- 1.7; women: 7.7 +/- 1.0) indicates the activation of osteoblastic bone formation. This study revealed an increase in cortical BMD at the forearm; in acromegalic patients; though trabecular BMD did not differ from controls. The differential mineralization of cortical and trabecular bone in acromegaly may be indicative of the detrimental effect accompanying pituitary insufficiency can have on trabecular bone, despite substitution therapy, but could also be due to different reactivity of cortical and trabecular bone to GH and/or IGF I. The observable increase of bone mineral density in acromegaly suggests a potential use for GH in treating osteoporosis.
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PMID:Differential presentation of cortical and trabecular peripheral bone mineral density in acromegaly. 936 Sep 37

Growth hormone (GH) quantitation in biological fluids varies depending on the assays employed, and factors which may interfere in the assays include the high affinity GH-binding protein (GHBP). To evaluate this potential effect on GH estimates, we studied the influence of adding increasing amounts of high affinity glycosylated GHBP to normal, acromegalic and GH-deficient sera, which were then processed in four different immunoassays. Two commercial immunometric assays, Delfia and Nichols (assays 1 and 2), and two RIAs, one using a polyethylene glycol (PEG) precipitation (assay 3) and one using wick-chromatography (assay 4) for separation of free and bound 125I-GH, were employed. In the Delfia assays, GH estimates of 11 sera decreased (p < 0.05) to 87.2 +/- 2.6%, 73.0 +/- 2.7% and 60.1 +/- 2.5% (mean +/- SEM) of basal GH estimates with the addition of GHBP in concentrations of 0.54, 2.14 and 6.42 nmol/l, respectively. In the Nichols assay, GH estimates were not significantly reduced (93.4 +/- 2.6%, 83.8 +/- 4.5% and 83.9 +/- 3.9%) with the applied GHBP concentrations. In assay 3 (RIA), the addition of GHBP increased GH estimates to 122 +/- 10.0% and 167 +/- 19.1% (both p < 0.05) with the addition of GHBP in concentrations of 2.14 and 6.42 nmol/l, respectively, whereas an increase in GHBP concentration of 0.54 nmol/l did not change the estimates from basal levels (99.0 +/- 4.8%, p > 0.05). In assay 4 (RIA), the addition of GHBP induced decreased GH estimates. With this varying influence of GHBP on GH estimates, binding protein interference should be taken into consideration when comparing GH estimates obtained with many currently utilized GH immunoassays. The present results demonstrate that GHBP levels within physiological range may interfere with the results of GH assays, giving either spuriously high or low values depending on the GH assay methodology.
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PMID:Influence of growth hormone binding protein on growth hormone estimation in different immunoassays. 981 86

In animals, it has been demonstrated that nitric oxide (NO) is a potent neuroregulatory substance. By intravenous infusion, L-arginine is converted to NO and citrulline, but it is unknown whether NO is responsible for the GH stimulating effect of L-arginine in humans. We investigated whether intravenous infusion of the NO synthase inhibitor N-monomethyl-L-arginine (L-NMMA) influenced L-arginine stimulated GH secretion. Ten healthy men, aged 28.6 +/- 1.9 (mean +/- SEM) years were examined twice. L-arginine was infused intravenously in a dose of 0.5 g/kg, max 35 g, from 0 to 30 min, accompanied by either: (1) L-NMMA from -5 to 0 min, in a dose of 3 mg/kg, max 250 mg, and in a dose of 3.5 mg/kg, max 250 mg from 0 to 60 min; or (2) a saline infusion. Heart rate increased (P = 0.032), and diastolic blood pressure decreased (P < 0.001) in the two situations. Plasma cGMP was unchanged and identical in the two situations (P = 0.679). Urine cGMP/creatinine ratio increased during both examinations (P = 0.041). Growth hormone secretion increased significantly during L-arginine infusion (P = < 0.001) without any effect of L-NMMA (P = 0.848). We did not find evidence that NO influences GH secretion. It remains to be tested, however, whether a higher dose of L-NMMA may influence L-arginine stimulated GH secretion.
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PMID:L-arginine-induced growth hormone secretion is not influenced by co-infusion of the nitric oxide synthase inhibitor N-monomethyl-L-arginine in healthy men. 1020 10

The pathogenesis of growth failure in Turner's syndrome is not clear but might be attributed to a decreased sensitivity to insulin-like growth factor-I (IGF-I) in distinct cell lines or to its reduced autocrine/paracrine action. Growth hormone (GH) therapy leads to increments in IGF-I levels and to growth acceleration. In order to evaluate the pattern of overcoming IGF-I resistance through childhood and adolescence, we measured IGF-I in 78 girls with Turner's syndrome aged 4.6-18.3 years on 160 occasions without or during GH (1 IU/kg/week [0.33 mg/kg/week]) or GH+estradiol (E2) therapy and compared them with local IGF-I standards. In untreated patients, IGF-I levels were low normal (-0.71+/-0.18 SDS, mean +/- SEM). In both GH or GH+E2 treated girls, circulating IGF-I levels were persistently supraphysiological (GH only: +3.61+/-0.23 SDS; GH + estradiol: +3.18+/-0.31 SDS). The age-dependent pattern of IGF-I secretion was conserved but the pubertal increase occurred earlier. The highest standardized IGF-I levels were observed at age 8.5-9.4 years (+6.62+/-1.00 SDS) and 9.5-10.4 years (+5.61+/-1.03 SDS). GH+E2 substitution had no additional effect on circulating IGF-I. We conclude that high IGF-I levels are needed to overcome the IGF-resistance in Turner's syndrome. They reflect the action of GH therapy but not of estrogens. The earlier pubertal increase of IGF-I might be caused by exaggerated adrenal androgens.
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PMID:IGF-I resistance and Turner's syndrome. 1122 Jul 3

The present clinical study implements a novel interventional strategy of short-term profound and selective blockade of GH receptors to reduce plasma insulin-like growth factor I (IGF-I) concentrations reversibly in healthy eumetabolic adults. Thereby, we examine the feedback role of systemic IGF-I on GH secretion without introducing the complex metabolic disarray that can otherwise accompany secondary IGF-I deprivation. To this end, we sampled blood at 10-min intervals for 10 h overnight in 8 men (aged 19-46 yr) and 4 women (aged 19-39 yr) to quantitate endogenous GH secretion and half-life 72 h after the prospective, randomly ordered, double blind, and within-subject cross-over administration of pegvisomant (1 mg/kg) or saline (0.5 mL) sc. Pegvisomant is an oligopegylated recombinant human GH peptide mutated to antagonize GH receptor-dependent signaling. Statistical analyses of paired plasma IGF-I concentrations and deconvolution-based quantitation of pulsatile GH secretion revealed that GH receptor blockade 1) suppressed fasting total IGF-I concentrations by 31%, viz. from (mean +/- SEM) 276 +/- 42 (placebo) to 190 +/- 20 microg/L (pegvisomant; P = 0.006) 84 h after drug injection; 2) increased the 10-h mean serum GH concentration by 71% from 1.4 +/- 0.33 (placebo) to 2.4 +/- 0.58 (pegvisomant; P = 0.024); 3) augmented the amplitude of underlying GH secretory bursts by 2.1-fold (i.e. from 0.13 +/- 0.032 to 0.27 +/- 0.076 microg/L.min; P = 0.0088); and 4) elevated the basal/nonpulsatile rate of GH secretion by 2.5-fold (from 2.3 +/- 0.77 to 5.07 +/- 1.8 microg/L.10 h; P = 0.022). The rise in the amplitude of GH secretory bursts correlated with the fall in plasma IGF-I concentrations (r = 0.603; P = 0.038). In contrast, IGF-I depletion did not alter GH secretory pulse frequency, half-duration, interpulse interval, percentage of pulsatile GH release, or half-life of endogenous GH. In summary, selective short-term reduction of systemic IGF-I concentrations in healthy eumetabolic adults drives GH secretion via the specific bipartite neuroregulatory mechanism of amplified GH secretory burst amplitude and elevated basal/nonpulsatile GH release. Endogenous GH half-life and frequency-related features of pulsatile GH secretion are not measurably affected, thus identifying a highly distinctive mode of IGF-I feedback-dependent control of GH output. As the increment in GH secretory burst amplitude correlated with the decrement in plasma IGF-I concentrations, we infer that variations in circulating IGF-I availability within the adult midphysiological range can influence pulsatile and basal GH production by way of negative feedback. Based on data in experimental animals, we speculate that the negative feedback actions of systemic IGF-I on GH secretion are mediated via increased hypothalamic somatostatin release, decreased GHRH (or GH-releasing peptide) secretion, and/or suppressed pituitary GH biosynthesis.
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PMID:Lowering total plasma insulin-like growth factor I concentrations by way of a novel, potent, and selective growth hormone (GH) receptor antagonist, pegvisomant (B2036-peg), augments the amplitude of GH secretory bursts and elevates basal/nonpulsatile GH release in healthy women and men. 1144 5

Organs that respond to and metabolize GH are enriched in cognate high-affinity receptors. However, whether isologous receptors mediate the de facto access of ligand to cellular degradative pathways is not known. To address this query, we assessed the distribution and whole-body elimination kinetics of (endogenous and exogenous) GH before and after administration of a novel, potent, and selective recombinant human (rh) GH receptor antagonist peptide, pegvisomant. Sixteen healthy young adults (nine men and seven women) participated in a double-blind, prospectively randomized, within-subject cross-over study. The intervention comprised a single sc injection of placebo vs. a high dose of pegvisomant (1 mg/kg sc) timed 62 and 74 h before the overnight sampling and daytime infusion sessions, respectively. The half-life, metabolic clearance rate (MCR), and distribution volume of GH were quantitated by way of: 1) deconvolution analysis of serum GH concentration time series collected every 10 min for 10 h; 2) exponential regression analysis of the decay of GH concentrations after a 6-min iv pulse of rhGH (1 and 10 micro g/kg); 3) calculation of the MCR during constant iv infusion of rhGH (0.5 and 5.0 micro g/kg every 2 h); and 4) exponential fitting of the elimination time-course of GH concentrations following cessation of each constant infusion. Concentrations of GH and pegvisomant were measured in separate, noncross-reactive, two-site monoclonal, immunofluorometric assays. Pegvisomant concentrations averaged 4860 +/- 480 micro g/liter (+/-SEM) across the infusion interval, thus exceeding low steady state GH concentrations by 3000-fold. Inhibitory efficacy of the GH receptor antagonist peptide was affirmed by way of a 34% reduction in the serum total IGF-I concentration, i.e., from 257 +/- 37 (placebo) to 170 +/- 24 (drug) micro g/liter (P < 0.001); and a reciprocal 77% elevation of the (10-h) mean GH concentration, i.e., from 1.3 +/- 0.23 (placebo) to 2.3 +/- 0.42 (drug) micro g/liter (P = 0.003). ANOVA disclosed that prior administration of pegvisomant (compared with placebo) did not alter: 1) the calculated half-life (minutes) of secreted GH, which averaged 15 +/- 1.3 (placebo) and 14 +/- 0.69 (drug); 2) the half-time of disappearance (minutes) of an iv pulse of rhGH, 15 +/- 1.0 (placebo) and 13 +/- 0.5 (drug) (for the 10 micro g/kg dose); 3) the distribution volume (milliliters per kilogram) of rhGH, 59 +/- 6.2 (placebo) and 58 +/- 3.5 (drug); 4) the steady state GH concentration (micrograms per liter) attained during constant iv infusion of rhGH (at a rate of 5 micro g/kg every 2 h), 18.2 +/- 2.4 (placebo) and 18.3 +/- 2.3 (drug); 5) the half-life (minutes) of elimination of GH from equilibrium, 16 +/- 0.98 (placebo) and 16 +/- 1.8 (drug); and 6) the steady state MCR (liters per kilogram per day) of rhGH, 3.8 +/- 0.32 (placebo) and 3.5 +/- 0.31 (drug). In ensemble, the present data refute the a priori postulate that vascular-accessible GH receptors determine the in vivo pseudoequilibrium kinetics of GH disappearance in the human.
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PMID:Impact of experimental blockade of peripheral growth hormone (GH) receptors on the kinetics of endogenous and exogenous GH removal in healthy women and men. 1246 80

The aim of this work was to determine the kinetics of the dramatic development of the gill chloride cells (CCs) during adaptation of the salmonid Oncorhynchus mykiss to an ion-poor environment.To monitor cell division, the incorporation in the mitotic cell DNA of bromo-deoxyuridine (BrdUrd) was visualized with a monoclonal antibody. The density of labelled nuclei was used as an index of cellular division (proliferation), concomitantly with morphometry of phenotypic changes monitored with SEM.In the filament epithelium, a phase of CC differentiation occurred within 12h after the transfer, followed by a delayed phase of cell proliferation (48h). In the lamellar epithelium, the present study demonstrates the absence of cell proliferation after ion-poor water transfer. The conclusion is that proliferation (mitosis) is important in the primary filament whereas differentiation and migration (from the filament) is the main mechanism for the appearance of CCs on the secondary lamellae.The present study suggests that cortisol promoted differentiation, but not division, of cells. CCs, presumably premature, were stained by anti-cortisol monoclonal antibody indicating the presence of cortisol. No mature CCs were stained.Growth hormone (oGH, ratGH) increased the rate of cell division both in lamellar and filament epithelium.
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PMID:Gill epithelial cells kinetics in a freshwater teleost, Oncorhynchus mykiss during adaptation to ion-poor water and hormonal treatments. 2419 72


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