Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 11 to 20 of 20

Publication Record

Connections

The effects of growth hormone and insulin-like growth factor-1 on the aging cardiovascular system and its progenitor cells.
Devin JK, Young PP
(2008) Curr Opin Investig Drugs 9: 983-92
MeSH Terms: Aged, Aging, Animals, Cardiovascular Diseases, Cardiovascular Physiological Phenomena, Clinical Trials as Topic, Growth Hormone, Hormone Replacement Therapy, Human Growth Hormone, Humans, Indoles, Insulin-Like Growth Factor I, Myocytes, Smooth Muscle, Risk, Spiro Compounds, Stem Cell Transplantation, Stem Cells
Show Abstract · Added December 10, 2013
Aging is a major risk factor for the development of cardiovascular disease. Aging is also associated with a decline in the growth hormone (GH) and insulin-like growth factor-1 (IGF-1) axis. This axis impacts endothelial and vascular smooth muscle cell biology, as well as cardiac function. The number of endothelial progenitor cells (EPCs) also decreases with age and is emerging as a surrogate measurement of vascular senescence. Studies suggest that EPCs impact vascular health by modulating vascular repair and function. Current evidence demonstrates that EPC number and function is restored with a GH-mediated increase in serum IGF-1. Modulation of the GH and IGF-1 system may therefore provide a useful therapy in the prevention of age-associated changes in the cardiovascular system and in future regenerative cell-based therapies.
0 Communities
1 Members
0 Resources
17 MeSH Terms
Isolated growth hormone deficiency type II caused by a point mutation that alters both splice site strength and splicing enhancer function.
Shariat N, Holladay CD, Cleary RK, Phillips JA, Patton JG
(2008) Clin Genet 74: 539-45
MeSH Terms: Cells, Cultured, Child, Preschool, Exons, Female, Human Growth Hormone, Humans, Infant, Male, Metabolic Diseases, Mutation, Pedigree, Point Mutation, RNA Interference, RNA Splice Sites, RNA Splicing
Show Abstract · Added May 27, 2014
A heterozygous single base mutation in the human growth hormone (GH) gene (GH-1) was identified in a family presenting with isolated GH deficiency type II (IGHD II). Affected individuals have a guanine to adenine transition at the first nucleotide of exon 3 (E3+1 G-->A) that results in exon skipping and production of a dominant-negative 17.5-kDa isoform. We show that the mechanistic basis for exon skipping is due to the unique position of this mutation because it weakens the 3' splice site and simultaneously disrupts a splicing enhancer located within the first seven bases of exon 3. A G-->T mutation at this same position not only affects splicing but also results in a premature stop codon for those transcripts that include exon 3. Thus, mutations that alter the first nucleotide of exon 3 illustrate the various mechanisms by which changes in sequence can cause disease: splice site selection, splicing enhancer function, messenger RNA decay, missense mutations, and nonsense mutations. For IGHD II, only exon skipping leads to production of the dominant-negative isoform, with increasing skipping correlating with increasing disease severity.
0 Communities
1 Members
0 Resources
15 MeSH Terms
Low-dose growth hormone administration mobilizes endothelial progenitor cells in healthy adults.
Devin JK, Vaughan DE, Blevins LS, Chen Q, Covington J, Verity DK, Young PP
(2008) Growth Horm IGF Res 18: 253-63
MeSH Terms: Adult, Aged, Cell Movement, Cells, Cultured, Drug-Related Side Effects and Adverse Reactions, Endothelial Cells, Female, Health, Human Growth Hormone, Humans, Male, Middle Aged, Nitric Oxide, Prospective Studies, Stem Cells
Show Abstract · Added December 10, 2013
OBJECTIVE - Endothelial progenitor cells (EPCs) mobilize from the bone marrow secondary to a stimulus and home to sites of injury, where they differentiate into endothelial cells and contribute to the repair of damaged vasculature. We hypothesized that growth hormone (GH) administration would increase the number of circulating EPCs in adults and thereby represent a mechanism to enhance vascular health.
DESIGN - A prospective trial of low-dose GH (0.03mg/kg/week for 4 weeks followed by 0.06mg/kg/week for a maximum of four additional weeks) in 10 healthy adults (6 males and 4 females; mean age 37 years, range 26-65). Primary outcomes measured included the number of circulating EPCs as assessed by colony-forming unit (CFU) assay and flow cytometry. Secondary outcomes included plasma measurements of known mediators of EPC mobilization and indices of nitric oxide (NO). Outcomes were measured at baseline and at study completion.
RESULTS - GH administration increased serum IGF-1 (143ng/mL [IQR 121-164] to 222 [IQR 194-244]; P=0.005). The increase in early-outgrowth EPCs (13 CFU per high-power field [IQR 6-24] to 19 [IQR 13-40]; P=0.005) correlated with the peak IGF-1 after adjustment for the baseline number of early-outgrowth EPCs (r=0.719 [95% CI 0.06, 0.93]; P=0.027). The number of late-outgrowth EPCs as well as CD34+, VEGFR2(KDR)+, and AC133+ cells did not significantly change. Other mediators of EPC mobilization were stable while plasma nitrite trended upwards (1.3micromol/L [IQR 0-2.5] to 3.7 [IQR 2.2-8.9]; P=0.052).
CONCLUSIONS - GH administration selectively augments the early-outgrowth EPC population in healthy individuals. These findings both support GH replacement in the setting of GH deficiency to maintain vascular integrity and have implications for the use of GH in future regenerative cell-based therapies. Furthermore, the decrease in EPCs observed with aging may in part be explained by the declining somatotropic axis, and thereby contribute to cardiovascular senescence.
0 Communities
1 Members
0 Resources
15 MeSH Terms
Rescue of pituitary function in a mouse model of isolated growth hormone deficiency type II by RNA interference.
Shariat N, Ryther RC, Phillips JA, Robinson IC, Patton JG
(2008) Endocrinology 149: 580-6
MeSH Terms: Animals, Disease Models, Animal, Dwarfism, Pituitary, Genetic Therapy, Human Growth Hormone, Humans, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microscopy, Electron, Pituitary Gland, Anterior, RNA Interference, Recovery of Function
Show Abstract · Added August 13, 2010
Splicing mutations in the human GH (hGH) gene (GH-1) that cause skipping of exon 3 result in a form of GH deficiency termed isolated GH deficiency type II (IGHD II). The GH-1 gene contains five exons; constitutive splicing produces the wild-type 22-kDa hormone, whereas skipping of exon 3 results in transcripts encoding a 17.5-kDa isoform that acts as a dominant-negative to block secretion of the wild-type hormone. Common characteristics of IGHD II include short stature due to impaired bone elongation, growth, and, in severe cases, anterior pituitary hypoplasia. Typically, IGHD II is treated by sc delivery of hGH, which can rescue stature but, unfortunately, does not inhibit pituitary hypoplasia. Direct destruction of transcripts encoding the dominant-negative 17.5-kDa isoform should both rescue stature and prevent hypoplasia. Here, we have used delivery of short hairpin RNAs to rescue a murine model of IGHD II by specifically targeting transcripts encoding the 17.5-kDa isoform using RNA interference. To our knowledge, this is the first example where a short hairpin RNA has been expressed to specifically degrade an incorrectly spliced transcript and rescue a dominant-negative disease phenotype in vivo.
1 Communities
1 Members
0 Resources
13 MeSH Terms
Recombinant human growth hormone improves muscle amino acid uptake and whole-body protein metabolism in chronic hemodialysis patients.
Pupim LB, Flakoll PJ, Yu C, Ikizler TA
(2005) Am J Clin Nutr 82: 1235-43
MeSH Terms: Adult, Amino Acids, Carbon Isotopes, Cross-Over Studies, Energy Metabolism, Exercise, Female, Human Growth Hormone, Humans, Kidney Failure, Chronic, Male, Muscle, Skeletal, Oxidation-Reduction, Oxygen Consumption, Parenteral Nutrition, Proteins, Recombinant Proteins, Renal Dialysis, Treatment Outcome
Show Abstract · Added September 29, 2014
BACKGROUND - Intradialytic parenteral nutrition (IDPN), with or without exercise, has been shown to reverse the net negative whole-body and forearm muscle protein balances observed during hemodialysis. Pharmacologic doses of recombinant human growth hormone (rhGH) constitute another potential anabolic therapy in chronic hemodialysis patients.
OBJECTIVE - Our goal was to examine the potential additive anabolic effects of rhGH compared with IDPN and exercise on protein and energy homeostasis.
DESIGN - We studied 7 chronic hemodialysis patients in a crossover design study in which each subject participated in 2 protocols: GH (rhGH + IDPN + exercise) and no GH (IDPN + exercise). During the GH protocol, the subjects were studied after 3 daily doses of rhGH. Each subject was studied 2 h before, 4 h during, and 2 h after a hemodialysis session with the use of a primed, constant infusion of l-[1-(13)C]leucine.
RESULTS - Whole-body net protein balance was -0.50 +/- 0.07 mg x kg fat-free mass(-1) x min(-1) when the patients did not receive rhGH and -0.39 +/- 0.04 mg x kg fat-free mass(-1) x min(-1) when the patients received rhGH, a 22% improvement in prehemodialysis whole-body protein homeostasis (P < 0.05). Essential amino acid muscle loss was also significantly less during the prehemodialysis period when rhGH was administered (-18 +/- 23 compared with -71 +/- 20 mmol/L; P < 0.05). The whole-body anabolic effects of rhGH observed during the prehemodialysis period persisted throughout the entire study, as evidenced by a lack of significant interaction or main effect of treatment during hemodialysis and in the posthemodialysis period.
CONCLUSION - rhGH improves whole-body protein homeostasis in chronic hemodialysis patients.
0 Communities
1 Members
0 Resources
19 MeSH Terms
Genetic polymorphisms in the human growth hormone-1 gene (GH1) and the risk of breast carcinoma.
Ren Z, Cai Q, Shu XO, Cai H, Cheng JR, Wen WQ, Gao YT, Zheng W
(2004) Cancer 101: 251-7
MeSH Terms: Asian Continental Ancestry Group, Breast Neoplasms, Case-Control Studies, Female, Gene Frequency, Genetic Predisposition to Disease, Human Growth Hormone, Humans, Middle Aged, Odds Ratio, Polymorphism, Genetic, Promoter Regions, Genetic
Show Abstract · Added December 10, 2013
BACKGROUND - In addition to possessing many physiologic functions, human growth hormone-1 (GH1) has been shown in recent in vitro and in vivo experiments to induce malignant disease, including breast carcinoma. The authors investigated the association of breast carcinoma with genetic polymorphisms in the GH1 gene in the Shanghai Breast Cancer Study.
METHODS - Included in the current investigation were 1193 women with breast carcinoma (case patients) and 1310 healthy women from the same community (control patients) who completed in-person interviews and provided blood samples. Genetic polymorphisms in the proximal promoter region (nucleotide [nt] -162 to nt +148 relative to the transcription start site of the GH1 gene) were searched and confirmed by resequencing DNA samples from 43 study participants. A novel polymorphism, a transition from adenine to guanine at nt 69 (A69G), was identified. Samples from all participants were genotyped with TaqMan 5' nuclease assays for five common single-nucleotide polymorphisms (SNPs)-four in the proximal region (A-75G, G-57T, A-6G, and A69G) and one in intron 4 (T1169A).
RESULTS - The frequencies of occurrence for the minor alleles in these polymorphic sites were 0.04, 0.60, 0.24, 0.03, and 0.34, respectively, in the control group; these frequencies were comparable to those observed in the case group. After adjusting for potential confounding factors, none of the SNPs investigated in this study showed a statistically significant association with breast carcinoma risk. This null association was found for both younger women (age < 45 years) and older women (age > or = 45 years). GH1 gene haplotypes were assessed using SNP data and were analyzed in relation to breast carcinoma risk. Again, none of the haplotypes were associated with breast carcinoma risk.
CONCLUSIONS - The results of the current study suggest that genetic polymorphisms in the proximal promoter region and in the fourth intron of the GH1 gene are unrelated to breast carcinoma risk in Chinese women.
Copyright 2004 American Cancer Society.
0 Communities
2 Members
0 Resources
12 MeSH Terms
Recombinant human growth hormone in patients with acute renal failure.
Saadeh E, Ikizler TA, Shyr Y, Hakim RM, Himmelfarb J
(2001) J Ren Nutr 11: 212-9
MeSH Terms: Acute Kidney Injury, Blood Urea Nitrogen, Critical Care, Female, Hospitalization, Human Growth Hormone, Humans, Insulin-Like Growth Factor I, Male, Middle Aged, Nitrogen, Nutrition Disorders, Nutritional Status, Pilot Projects, Prospective Studies, Proteins, Serum Albumin
Show Abstract · Added May 20, 2014
OBJECTIVE - The objective of this study is to determine the impact of recombinant human growth hormone (rhGH) on metabolic and nutritional parameters in malnourished patients with acute renal failure.
DESIGN - The design is an open-labeled pilot trial examining the effects of rhGH administration in a small group of highly catabolic, malnourished patients with acute renal failure. Each patient served as his or her own control.
SETTING - An intensive care unit in a tertiary care medical institution.
PATIENTS - Five patients with established acute renal failure in a critical care unit. Entry criteria included clinical evidence of malnutrition: a serum albumin level of <3.2 g/dL, a prealbumin level of < or = 20 mg/dL, and an insulin-like growth factor IGF 1 level <200 ng/mL. The study consisted of 3 periods: phase I, 3 day baseline; phase II, 6 day treatment; and phase III, 3 day washout. During the entire study, blood and urine samples were obtained daily to calculate normalized protein catabolic rate, total nitrogen appearance rate (TNA), and nitrogen balance. Additional data were collected to measure metabolic and inflammatory parameters.
INTERVENTION - The intervention consisted of administering 100 microg/kg/d of rhGH for 6 days.
RESULTS - There were significant changes in TNA, normalized protein catabolic rate, and nitrogen balance during the 3 study phases. TNA decreased from 43.3 +/- 24.4 g/d in phase I, to 25.2 +/- 16.5 g/d during phase II (P <.001). There was a further decrease in TNA to 16.2 +/- 8.3 g/d during phase III (P <.001 v phase I). Nitrogen balance improved from - 31.8 +/- 21.4 g/d during phase I, to - 12.9 +/- 10.3 g/d during phase II (P <.001), and further improved to - 4.1 +/- 4.0 g/d in phase III (P <.001 v phase I). Significant changes were also noted in levels of blood urea nitrogen, phosphorous, serum growth hormone, IGF-1, and serum leptin levels after growth hormone administration. A statistically significant increase in serum albumin was noted in phase III (3.1 g/dL) versus phase I (2.7 +/- 0.7 g/dL).
CONCLUSIONS - Administration of rhGH to critically ill patients with acute renal failure resulted in improvements in negative nitrogen balance and a significant decrease in total nitrogen appearance rate. These changes corresponded to increases in serum growth hormone, IGF-1, IGF-1 binding protein 3, and leptin levels after growth hormone administration.
Copyright 2001 by the National Kidney Foundation, Inc.
0 Communities
2 Members
0 Resources
17 MeSH Terms
An endocrine-exocrine switch in the activity of the pancreatic homeodomain protein PDX1 through formation of a trimeric complex with PBX1b and MRG1 (MEIS2).
Swift GH, Liu Y, Rose SD, Bischof LJ, Steelman S, Buchberg AM, Wright CV, MacDonald RJ
(1998) Mol Cell Biol 18: 5109-20
MeSH Terms: Animals, Cell Line, Cells, Cultured, DNA-Binding Proteins, Enhancer Elements, Genetic, Gene Expression Regulation, Gene Library, Globins, HeLa Cells, Homeodomain Proteins, Human Growth Hormone, Humans, Islets of Langerhans, Mice, Pancreas, Pancreatic Elastase, Promoter Regions, Genetic, RNA, Messenger, Rats, Recombinant Fusion Proteins, Repressor Proteins, Trans-Activators, Transcription, Genetic, Transfection, Xenopus laevis
Show Abstract · Added June 11, 2010
HOX proteins and some orphan homeodomain proteins form complexes with either PBX or MEIS subclasses of homeodomain proteins. This interaction can increase the binding specificity and transcriptional effectiveness of the HOX partner. Here we show that specific members of both PBX and MEIS subclasses form a multimeric complex with the pancreatic homeodomain protein PDX1 and switch the nature of its transcriptional activity. The two activities of PDX1 are exhibited through the 10-bp B element of the transcriptional enhancer of the pancreatic elastase I gene (ELA1). In pancreatic acinar cells the activity of the B element requires other elements of the ELA1 enhancer; in beta-cells the B element can activate a promoter in the absence of other enhancer elements. In acinar cell lines the activity is mediated by a complex comprising PDX1, PBX1b, and MRG1 (MEIS2). In contrast, beta-cell lines are devoid of PBX1b and MRG1, so that a trimeric complex does not form, and the beta-cell-type activity is mediated by PDX1 without PBX1b and MRG1. The presence of specific nuclear isoforms of PBX and MEIS is precisely regulated in a cell-type-specific manner. The beta-cell-type activity can be detected in acinar cells if the B element is altered to retain binding of PDX1 but prevent binding of the PDX1-PBX1b-MRG1 complex. These observations suggest that association with PBX and MEIS partners controls the nature of the transcriptional activity of the organ-specific PDX1 transcription factor in exocrine versus endocrine cells.
1 Communities
1 Members
0 Resources
25 MeSH Terms
Effect of aging on the sensitivity of growth hormone secretion to insulin-like growth factor-I negative feedback.
Chapman IM, Hartman ML, Pezzoli SS, Harrell FE, Hintz RL, Alberti KG, Thorner MO
(1997) J Clin Endocrinol Metab 82: 2996-3004
MeSH Terms: 3-Hydroxybutyric Acid, Adult, Aging, Blood Glucose, Dose-Response Relationship, Drug, Fatty Acids, Nonesterified, Feedback, Female, Glucose, Human Growth Hormone, Humans, Hydroxybutyrates, Infusions, Intravenous, Insulin, Insulin-Like Growth Factor I, Male, Osmolar Concentration, Recombinant Proteins
Show Abstract · Added February 28, 2014
To determine the effect of aging on the suppression of GH secretion by insulin-like growth factor (IGF)-I, we studied 11 healthy young adults (6 men, 5 women, mean +/- SD: 25.2 +/- 4.6 yr old; body mass index 23.7 +/- 1.8 kg/m2) and 11 older adults (6 men, 5 women, 69.5 +/- 5.8 yr old; body mass index 24.2 +/- 2.5 kg/m2). Saline (control) or recombinant human IGF-I (rhIGF-I) (2 h baseline then, in sequence, 2.5 h each of 1, 3, and 10 micrograms/kg.h) was infused iv during the last 9.5 h of a 40.5-h fast; serum glucose was clamped within 15% of baseline. Baseline serum GH concentrations (mean +/- SE: 3.3 +/- 0.7 vs. 1.9 +/- 0.5 micrograms/L, P = 0.02) and total IGF-I concentrations (219 +/- 15 vs. 103 +/- 19 micrograms/L, P < 0.01) were higher in the younger subjects. In both age groups, GH concentrations were significantly decreased by 3 and 10 micrograms/kg.h, but not by 1 microgram/kg.h rhIGF-I. The absolute decrease in GH concentrations was greater in young than in older subjects during the 3 and 10 micrograms/kg.h rhIGF-I infusion periods, but both young and older subjects suppressed to a similar GH level during the last hour of the rhIGF-I infusion (0.78 +/- 0.24 microgram/L and 0.61 +/- 0.16 microgram/L, respectively). The older subjects had a greater increase above baseline in serum concentrations of both total (306 +/- 24 vs. 244 +/- 14 micrograms/L, P = 0.04) and free IGF-I (8.5 +/- 1.4 vs. 4.2 +/- 0.6 micrograms/L, P = 0.01) than the young subjects during rhIGF-I infusion, and their GH suppression expressed in relation to increases in both total and free serum IGF-I concentrations was significantly less than in the young subjects. We conclude that the ability of exogenous rhIGF-I to suppress serum GH concentrations declines with increasing age. This suggests that increased sensitivity to endogenous IGF-I negative feedback is not a cause of the decline in GH secretion that occurs with aging.
0 Communities
1 Members
0 Resources
18 MeSH Terms
Transgenic studies with a keratin promoter-driven growth hormone transgene: prospects for gene therapy.
Wang X, Zinkel S, Polonsky K, Fuchs E
(1997) Proc Natl Acad Sci U S A 94: 219-26
MeSH Terms: Adult, Animals, Body Weight, Evaluation Studies as Topic, Gene Expression, Genetic Therapy, Human Growth Hormone, Humans, In Situ Hybridization, Keratinocytes, Keratins, Mice, Mice, Transgenic, Organ Size, Promoter Regions, Genetic, Protein Processing, Post-Translational, RNA, Messenger, Radioimmunoassay, Skin, Skin Transplantation, Tissue Distribution
Show Abstract · Added June 9, 2010
Keratinocytes are potentially appealing vehicles for the delivery of secreted gene products because they can be transferred to human skin by the relatively simple procedure of grafting. Adult human keratinocytes can be efficiently propagated in culture with sufficient proliferative capacity to produce enough epidermis to cover the body surface of an average adult. However, the feasibility of delivering secreted proteins through skin grafting rests upon (i) the strength of the promoter in keratinocytes and (ii) the efficiency of protein transport through the basement membrane of the stratified epithelium and into the bloodstream. In this paper, we use transgenic technology to demonstrate that the activity of the human keratin 14 promoter remains high in adult skin and that keratinocyte-derived human growth hormone (hGH) can be produced, secreted, and transported to the bloodstream of mice with efficiency that is sufficient to exceed by an order of magnitude the circulating hGH concentration in growing children. Transgenic skin grafts from these adults continue to produce and secrete hGH stably, at approximately 1/10 physiological levels in the bloodstream of nontransgenic recipient mice. These studies underscore the utility of the keratin 14 promoter for expressing foreign transgenes in keratinocytes and demonstrate that keratinocytes can be used as effective vehicles for transporting factors to the bloodstream and for eliciting metabolic changes. These findings have important implications for considering the keratinocyte as a possible vehicle for gene therapy.
0 Communities
1 Members
0 Resources
21 MeSH Terms