Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholinergic agonists are known to potentiate GHRH-induced GH secretion, probably acting via inhibition of hypothalamic somatostatin release. Their effect is reduced in aging and in patients with Alzheimer's disease. This may be the consequence of age-related cholinergic impairment, which, in turn, could cause somatostatinergic hyperactivity leading to GH hyposecretion. As in Down syndrome (DS) neural alterations have been reported similar to those in aging, including cholinergic impairment, we verified the GH response to GHRH (1 microgram/kg i.v. at 0 min) alone or combined with pyridostigmine (PD), a cholinesterase inhibitor (60 and 120 mg, respectively, in children and adults, orally at -60 min) in 15 DS children (13.5 +/- 0.6 years) and in 11 DS young adults (24.0 +/- 1.2 years). Fifteen normal children (11.9 +/- 0.5 years), 15 normal adults (27.3 +/- 0.9 years) and 16 normal elderly (76.3 +/- 1.5 years) were studied as controls. IGF-I levels showed an age-related reduction both in DS (children vs. adults, mean +/- SEM:354.8 +/- 44.9 vs. 204.4 +/- 29.4 micrograms/l, p < 0.02) and in controls (normal children vs. normal adults vs. normal elderly:281.4 +/- 36.3 vs. 175.4 +/- 11.2 vs. 72.5 +/- 6.6 micrograms/l, p < 0.001). The GH response to GHRH in DS children was higher than in DS adults (areas under curve: 1,197.6 +/- 241.5 vs. 434.4 +/- 83.3 micrograms/l/h, p < 0.01). On the other hand, in normal subjects the GHRH-induced GH rise was similar in children and adults (1,056.2 +/- 128.4 vs. 800.8 +/- 124.5 micrograms/l/h) and both were higher than that in elderly subjects (296.0 +/- 61.0 micrograms/l/h, p < 0.001). PD enhanced the GH response to GHRH both in DS and in normal subjects (p < 0.005). The GH response to PD+GHRH was lower in DS adults than in DS children (1,068.1 +/- 145.7 vs. 1,897.4 +/- 198.8 micrograms/l/h, p < 0.001) as well as in normal elderly subjects with respect to that in normal children and normal adults (832.3 +/- 144.7 vs. 2,172.1 +/- 156.1 and 2,347.6 +/- 322.4 micrograms/l/h, respectively, p < 0.001). The GH response to GHRH alone or combined with PD in DS adults was lower (p < 0.01) than that in normal adults and similar to that in normal elderly subjects. In conclusion, the present data demonstrate that the stimulated GH secretion in DS undergoes an accelerated age-related reduction. They also suggest the existence of a precocious impairment of central cholinergic activity in DS, which, in turn, could cause somatostatinergic hyperactivity and reduced GH secretion.
 ...
PMID:The enhancing effect of pyridostigmine on the GH response to GHRH undergoes an accelerated age-related reduction in Down syndrome. 887 21

The objectives were to investigate whether insulin-dependent diabetes mellitus disrupts production of estradiol and activity of the insulin-like growth factor (IGF)-I system in individual ovarian follicles during the preovulatory period of the estrous cycle. Diabetes mellitus was induced with streptozocin (150 mg/kg) in seven cyclic gilts at 180 +/- 5 days of age. On Day 12 of the estrous cycle, insulin replacement therapy was withdrawn from three gilts and continued in four; four gilts served as normal controls. After ovary removal on Day 18, all follicles > or = 3 mm diameter were dissected free and cultured for 6 h in the presence of 280 ng testosterone for assessment of estradiol and IGF-I production and binding protein activity. Treatments did not affect corpora lutea number (15.4 +/- 0.8) or serum estradiol (5.8 +/- 0.8 pg/ml) on Day 18. There were no differences for any measure of follicular development between normal and insulin-treated diabetic gilts. Untreated diabetic gilts, compared to normal and insulin-treated diabetic gilts, had fewer total visible follicles (22.7 vs. 61.3 and 63.3; SEM = 8; p < 0.01) and reduced follicular diameter (3.4 vs. 4.4 and 4.2 mm; SEM = 0.3; p < 0.0001), respectively. Untreated diabetic gilts had a greater percentage of macroscopically atretic follicles than normal and insulin-treated diabetic gilts (75% vs. 47% and 36%; SEM = 10; p < 0.05). Untreated diabetes mellitus lowered estradiol (p < 0.01); however, effects of treatment on estradiol production were not significant when diameter was part of statistical models. When contents of IGF-I in follicular fluid and conditioned medium were summed after 6 h of culture, untreated diabetic pigs had lower IGF-I at all follicle diameters than pigs in the other treatments (p < 0.05). IGF binding protein (BP) activity was affected by diabetes mellitus, with untreated diabetic pigs having greater IGFBP-1 activity in medium and with both diabetic groups having greater IGFBP-2 activity in follicular fluid (p < 0.05). Activity of IGFBP-1 predominated in conditioned medium, and IGFBP-2 activity predominated in follicular fluid. IGFBP-3 was decreased in follicular fluid of atretic follicles and in medium of atretic follicles in all except the insulin-treated diabetic gilts; in these gilts it was increased in atretic follicles (treatment by atresia interaction; p < 0.05). In conclusion, estradiol was most related to size of the follicle; however, lowering of IGF-I regardless of follicle diameter and alterations in IGFBP activity suggest that diabetes affects IGF-I and its binding proteins differently from estradiol production. These alterations may explain reduced follicular growth and increased follicular atresia in diabetic pigs.
 ...
PMID:Depletion of insulin in streptozocin-induced-diabetic pigs alters estradiol, insulin-like growth factor (IGF)-I and IGF binding proteins in cultured ovarian follicles. 887 89

This study was conducted to determine the effects of acute and chronic administration of GH-releasing peptide-2 (D-Ala-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2, GHRP-2 or KP102) on GH responsiveness in male Holstein calves. In the dose response study of acute administration, six calves were injected iv with saline or 6.25, 12.5 and 25.0 micrograms/kg body weight (BW) of KP102. The GH AUC (area under curve, ng/ml.min, mean +/- SEM) for 60 min was significantly increased with 6.25 (676.3 +/- 125.6), 12.5 (1574.8 +/- 318.0) and 25.0 (1578.7 +/- 214.6) micrograms/kgBW of KP102 than with saline (78.6 +/- 36.1) (P < 0.01). GH responses were decreased by multiple injections of 12.5 micrograms/kgBW KP102 at every 2 h for 8 h. The GH AUC for 60 min was decreased from the first injection (1162.9 +/- 313.3) to the second injection (604.7 +/- 131.9), but the response was significantly higher for the first and second injections than the third (304.4 +/- 173.1) and fourth injections (320.7 +/- 144.2) (P < 0.05). In the chronic administration, 8 calves were implanted subcutaneously with osmotic pumps (Alzet pump). Each of the 4 calves was given with 12.5 micrograms/kgBW per hour KP102 and the other 4 calves served as the control. During the 14 day period, average daily gain was significantly increased (36.4%) over the control (P < 0.05). Food efficiency was not significant, but numerically higher (29.4%) than the control. The plasma GH concentration was not increased by chronic administration of KP102, but IGF-I appeared to increase in KP102-treated calves more than the control. These results suggest that the synthetic KP102 can be used for enhancing the growth performance in domestic animals.
 ...
PMID:Characteristics of growth hormone secretion responsiveness to growth hormone-releasing peptide-2 (GHRP-2 or KP102) in calves. 888 23

Correction of anemia with recombinant human erythropoietin (rhEPO) in patients with end-stage renal disease has been associated with improvement of several abnormalities in hypothalamo-hypophyseal functions. The aim of the present work was to evaluate the growth hormone (GH) responses to GH-releasing hormone (GHRH) and clonidine stimulation, as well as the baseline concentrations of insulin-like growth factor I(IGF-I), before and after the correction of anemia with rhEPO in a group of uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Nine clinically stable patients (1 male, 8 female; mean age 55.4 years; mean duration of CAPD 14.1 months) were studied. Twelve normal volunteers were studied as controls. GHRH and clonidine stimulation tests were performed prior to starting rhEPO and again after partial correction of anemia with rhEPO therapy (60-130 U/kg/week, s.c., for 12 weeks). Blood samples for GH were collected during 2 h after GHRH (100 micrograms i.v. in bolus) or clonidine (0.15 mg/m2, p.o.) administration. In basal plasma samples IGF-I concentrations were also measured. Mean (+/- SEM) blood hemoglobin concentration rose from 5.32 +/- 0.25 to 7.22 +/- 0.25 mmol/l (p < 0.001) after rhEPO treatment. GH responses to GHRH were characterized by marked differences in single patients when compared with the control group. However, the GH peak and the area under the secretory curves (AUC) of GH responses in CAPD patients (9.89 +/- 4.01 micrograms/l and 15.06 +/- 6.02 micrograms.h/l, respectively) did not differ from those obtained in control subjects (14.58 +/- 3.25 microgram/l and 16.94 +/- 4.31 microgram.h/l, respectively). The study after correction of anemia showed an evident potentiation of GH values that reached statistically significant values at 60 and 90 min. GH AUC after rhEPO therapy rose to 25.61 +/- 9.25 micrograms.h/l (p = 0.01). In control subjects, clonidine administration was followed by a GH release that reached a maximum at 90 min (7.67 +/- 2.24 micrograms/l). However, CAPD patients exhibited a blunted response to clonidine both before (2.00 +/- 0.78 microgram/l) and after (2.78 +/- 0.76 microgram/l, NS) correction of the anemia with rhEPO. On the other hand, IGF-I concentrations after rhEPO therapy (32.05 +/- 5.52 nmol/l) were not significantly different from those found prior to starting therapy (38.13 +/- 8.44 nmol/l). In conclusion, these results suggest that correction of the anemia with rhEPO therapy potentiates GH responses to direct pituitary stimulation with GHRH although it is unable to restore the blunted response of GH to clonidine that is found in CAPD patients.
 ...
PMID:Growth hormone responses to growth hormone-releasing hormone and clonidine before and after erythropoietin therapy in CAPD patients. 893 79

The objective was to investigate the effect of growth hormone (GH) administration on circulating levels of free insulin-like growth factors (IGFs) in healthy adults. Eight healthy male subjects were given placebo and two doses of GH (3 and 6 IU/m2 per day) for 14 days in a double-blind crossover study. Fasting blood samples were obtained every second day. Free IGF-I and IGF-II were determined by ultrafiltration of serum. Total IGF-I and IGF-II were measured after acid-ethanol extraction. In addition, GH, insulin, IGF binding protein 1 (IGFBP-1) and IGFBP-3 were measured. Serum-free and total IGF-I increased in a dose-dependent manner during the 14 days of GH administration. After 14 days, serum-free IGF-I values were 610 +/- 100 ng/l (mean +/- SEM) (placebo), 2760 +/- 190 ng/l (3 IU/ m2) and 3720 +/- 240 ng/l (6 IU/m2) (p = 0.0001 for 3 and 6 IU/m2 vs placebo; p = 0.004 for 3 IU/m2 vs 6 IU/m2). Total IGF-I values were 190 +/- 10 micrograms/l (placebo), 525 +/- 10 (3 IU/m2), and 655 +/- 40 micrograms/l (6 IU/m2) (p < 0.0001 for 3 and 6 IU/m2 vs placebo; p = 0.04 for 3 IU/m2). There were no differences in the levels of free or total IGF-II during the three study periods. Insulin-like growth factor binding protein 1 was decreased during GH administration (p = 0.04 for placebo vs 3 IU/m2; p = 0.006 for placebo vs 6 IU/m2). In conclusion, fasting serum free IGF-I increased dose dependently during GH administration and free IGF-I increased relatively more than total IGF-I. This may partly be due to the decrease in IGFBP-1.
 ...
PMID:Free and total insulin-like growth factors and insulin-like growth factor binding proteins during 14 days of growth hormone administration in healthy adults. 902 11

Neonatal brain development in the rat is adversely affected by malnutrition. Alterations in tissue binding of IGF-I in the malnourished brain were tested in rat pups from mothers who were fed a 20% protein diet (C) or a 4% protein diet (M) starting from day 21 of gestation and continued throughout suckling. IGF-I binding in both cortex and cerebellum decreased progressively in C and M groups from day 6 to day 13. At day 9, 11, and 13, the binding was significantly greater (p < 0.02) in M compared to C groups. To investigate whether these changes might be related to the alteration in receptor activity, membranes were incubated with 125I-IGF in the presence of excess insulin with or without unlabeled IGF-I. In the absence of insulin, specific IGF-I binding in the M group was increased by 41.8 +/- 13.8% (mean +/- SEM p < 0.05) relative to C group. Insulin produced a consistent but incomplete inhibition of binding in both C and M, of 75% and 67% respectively. In addition, the specific IGF-I binding in the presence of insulin was increased in M group by 70.2 +/- 9.4% relative to C, p < 0.05. To characterize the nature of this binding, cerebral cortical membranes, from both groups, incubated with 125I-IGF-I were cross-linked, and electrophoresed on 6% and 10% SDS-PAGE gels under reducing conditions. Autoradiography of the 6% gel showed two specific bands at 115 kD and 240 kD, consistent with monomeric and dimeric forms of the IGF-I receptor, which were inhibited by excess insulin. In contrast, a 10% gel showed an additional band at 35 kD (IGF-binding protein) that was not inhibited by insulin. In both gels, membrane preparations from the M group showed a heightened intensity of the bands relative to C. The increase in binding protein relative to the receptor suggests a disequilibrium that may limit the availability of exogenous IGF-I to the tissues.
 ...
PMID:Alteration in IGF-I binding in the cerebral cortex and cerebellum of neonatal rats during protein-calorie malnutrition. 905 67

Deflazacort is an oxazoline compound derived from prednisolone. We studied changes in kidney function, growth velocity, weight/height ratio, insulin-like growth factor (IGF-I), and IGF binding proteins before and after substitution of deflazacort for methylprednisone in 27 transplanted patients aged 3.1-20 years. Methylprednisone (mean +/- SEM 0.17 +/- 0.01 mg/kg per day) was replaced by deflazacort (0.29 +/- 0.01 mg/kg per day) for a period of 1-5 years. Calculated creatinine clearance did not change significantly during deflazacort treatment. Growth velocity increased from 2.6 +/- 0.5 cm/year to 5.2 +/- 0.7 cm/year (1st year) in 14 prepubertal patients. After 4 years of deflazacort treatment, height standard deviation score for chronological age did not change in 7 prepubertal patients. Mean weight/height ratio decreased by 50% (1st year) and remained reduced during follow-up. Serum IGF-I, IGF binding protein-3 (IGFBP3), IGF/IGFBP3 molar ratio, and IGF-I and II binding capacities showed no significant change; however in 5 of 6 patients IGFBP2 decreased during deflazacort therapy. Our findings suggest that immunosuppressive treatment with deflazacort is as effective as methylprednisone and may lead to an improvement in the growth prognosis of children with renal transplantation.
 ...
PMID:Effects of deflazacort immunosuppression on long-term growth and growth factors after renal transplantation. 920 81

The aim of this study was to verify the persistence in adulthood of GH deficiency diagnosed in childhood and treated with hGH in childhood and to study whether anatomical hypothalamic-pituitary alterations evaluated by magnetic resonance (MR) imaging could predict it. To this goal, in six GHD adults (3 males and 3 females aged 17.2-24.5 yr, BMI 21.8 +/- 1.3), we studied anterior pituitary hormone response to GHRH (1 microgram/kg iv)+pyridostigmine (120 mg po)+ GnRH (100 micrograms iv) +TRH (400 micrograms iv)+hCRH (100 micrograms iv) as well as brain MR imaging. In childhood, the diagnosis of severe isolated GHD had been done based on auxological findings as well as on GH response < 7 micrograms/L after two classical provocative stimuli. In the present study, hormonal responses showed the persistence of severe isolated GHD in 4 out of 6 patients (peak, mean +/- SEM: 3.8 +/- 0.6, range 2.6-4.8 micrograms/L). In these patients, IGF-I levels were found low or low-normal. In other 2 patients, a clear GH response to stimulation (peak: 51.3 and 43.0 micrograms/L, respectively) together with normal IGF-I levels were found. No other anterior pituitary hormone deficiency was present in all subjects. MR imaging showed pituitary hypoplasia in all patients with persistent GHD; in 2 out of them, pituitary stalk interruption and ectopic neurohypophysis was also present. On the other hand, MR imaging showed normal hypothalamo-pituitary morphology in the 2 subjects with normal somatotrope response. In conclusion, our present data indicate that testing with a potent stimulus such as GHRH+pyridostigmine is a reliable method to assess the persistence of GH deficiency which associates with anatomical hypothalamic-pituitary alterations at the MR imaging. Patients with transient GH deficiency in childhood and normal pituitary GH reserve in adulthood have normal hypothalamic-pituitary MR imaging.
 ...
PMID:Is the persistence of isolated GH deficiency in adulthood predicted by anatomical hypothalamic-pituitary alterations? 929 76

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.
 ...
PMID:Differential presentation of cortical and trabecular peripheral bone mineral density in acromegaly. 936 Sep 37

The aim of the present study was to verify the GH-releasing effect of Hexarelin, a synthetic hexapeptide, in newborns who are known to have GH hypersecretion likely due to hyperactivity of GHRH-secreting neurons while somatostatinergic activity seems not fully operative. We studied in 6 newborns (NB, 2.5 +/- 2.1 days), 12 prepubertal children (PC, 9.8 +/- 0.45 yr) and 12 young adults (YA, 28.2 +/- 0.2 yr) the GH response to Hexarelin (HEX, 2 micrograms/kg i.v.) compared to that observed after GHRH (1 microgram/kg i.v.) in 6 NB (4.2 +/- 0.4 days), 12 PC (9.9 +/- 0.6 yr) and 12 YA (31.0 +/- 1.3 yr). GH levels were assayed basally and 30 and 60 min after drug administration. In NB, mean (+/- SEM) basal GH levels were higher while IGF-I levels were lower than those recorded in PC and YA (GH: 34.8 +/- 1.9 vs 2.8 +/- 0.4 vs 1.4 +/- 0.4 micrograms/l, p < 0.0006; IGF-I: 36.3 +/- 1.9 vs 152.0 +/- 11.5 vs 175.8 +/- 15.3 micrograms/l, p < 0.0007); in the last two groups GH and IGF-I levels were similar. The mean delta GH peak after HEX in NB (32.8 +/- 4.7 micrograms/l) was similar to that in PC (34.6 +/- 4.3 micrograms/l) and lower (p < 0.01) than that in YA (56.2 +/- 7.4 micrograms/l). Delta GH peak after GHRH in NB (60.1 +/- 1.5) was higher than those in PC and YA (20.8 +/- 4.8 and 22.8 +/- 3.4 micrograms/l) (p < 0.005 and < 0.002, respectively). In NB, the GH response to HEX was lower (p < 0.005) than to GHRH while in PC and YA the somatotrope response to HEX was higher (p < 0.03 and 0.0004, respectively) than to GHRH. These data demonstrate that the GH-releasing effect of Hexarelin undergoes age-dependent variation being lower in newborns than in young adults, opposite to that observed after GHRH administration. The evidence that Hexarelin releases less GH than GHRH in newborns but not in prepubertal children and in young adults makes unlikely the hypothesis that the GH-releasing effect of this hexapeptide is mediated via endogenous GHRH release.
 ...
PMID:The GH-releasing effect of Hexarelin, a synthetic hexapeptide, in newborns is lower than in young adults. 940 5


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>