GH treatment to final height produces similar height gains in patients with SHOX deficiency and Turner syndrome: results of a multicenter trial.

Science.gov (United States)

Blum, Werner F; Ross, Judith L; Zimmermann, Alan G; Quigley, Charmian A; Child, Christopher J; Kalifa, Gabriel; Deal, Cheri; Drop, Stenvert L S; Rappold, Gudrun; Cutler, Gordon B

2013-08-01

Growth impairment in short stature homeobox-containing gene (SHOX) deficiency and Turner syndrome share a similar etiology. Because of the established effect of GH treatment on height in patients with Turner syndrome, we hypothesized that GH therapy would also stimulate growth in patients with SHOX deficiency. Our objectives were to evaluate long-term efficacy of GH treatment in short patients with SHOX deficiency and to compare the effect on final (adult) height (FH) in patients with SHOX deficiency and Turner syndrome. A prospective, multinational, open-label, randomized 3-arm study consisting of a 2-year control period and a subsequent extension period to FH. The treatment groups were 1) SHOX-D-C/GH (untreated during the control period, GH-treated during the extension), 2) SHOX-D-GH/GH, and 3) Turner-GH/GH (GH-treated during both study periods). Short-statured prepubertal patients with genetically confirmed SHOX deficiency (n = 49) or Turner syndrome (n = 24) who participated in the extension. Depending on the study arm, patients received a daily sc injection of 0.05 mg/kg recombinant human GH from start of the study or start of the extension until attainment of FH or study closure. Height SD score gain from start of GH treatment to FH was similar between the combined SHOX-deficient groups (n = 28, 1.34 ± 0.18 [least-squares mean ± SE]) and the Turner group (n = 19, 1.32 ± 0.22). In this FH population, 57% of the patients with SHOX deficiency and 32% of the patients with Turner syndrome achieved a FH greater than -2 SD score. GH treatment in short children with SHOX deficiency showed similar long-term efficacy as seen in girls with Turner syndrome.

Therapeutic Efficacy and Safety of GH in Japanese Children with Down Syndrome Short Stature Accompanied by GH Deficiency.

Science.gov (United States)

Meguri, Kyoko; Inoue, Masaru; Narahara, Koji; Sato, Takahiro; Takata, Ami; Ohki, Nobuhiko; Ozono, Keiichi

2013-10-01

In this study, we investigated the effects of GH treatment in children with Down syndrome who had been diagnosed with GH deficiency (GHD). A total of 20 subjects were investigated in this study. Fourteen Down syndrome children (5 boys and 9 girls) with short stature due to GHD were treated with GH at Okayama Red Cross General Hospital, and 6 Down syndrome children (4 boys and 2 girls) with short stature due to GHD were registered in the Pfizer International Growth Database (KIGS). Height SD score (SDS) increased throughout the three-year GH treatment period. The overall mean height SDS increased from -3.5 at baseline to -2.5 after 3 yr of treatment. The mean change in height SDS during these 3 yr was 1.1. In addition, height assessment of SD score based on Down syndrome-specific growth data in the Japanese population revealed that the height SDS (Down syndrome) also increased across the 3-yr GH treatment period. The mean change in height SDS (Down syndrome) during these three years was 1.3. GH therapy was effective for Down syndrome short stature accompanied by GHD, and no new safety concerns were found in this study.

GH-replacement therapy in adults

DEFF Research Database (Denmark)

Christiansen, J S; Jørgensen, J O; Pedersen, S A

1991-01-01

Growth hormone (GH) deficiency in adults, whether GH deficient since childhood or patients rendered GH deficient in adult life, is associated with psychosocial maladjustment, reduced muscle strength and reduced exercise capacity. Body composition is significantly altered with increased fat and de...

The GH-IGF1 axis and longevity. The paradigm of IGF1 deficiency.

Science.gov (United States)

Laron, Zvi

2008-01-01

Primary or secondary IGF1 deficiency has been implicated in shortening of lifespan. This paper reviews available data on the influence of IGF1 deficiency on lifespan and longevity in animals and man. It has been shown that inactivation of the IGF1 gene or of the GH receptor in both invertebrates (C-elegans, flies-Drosphila) and rodents (mice and rats), leading to IGF1 deficiency, prolong life, particularly in females. In man, evaluation of the 2 largest cohorts of patients with Laron syndrome (inactive GH receptor resulting in IGF1 deficiency) in Israel and Ecuador revealed that despite their dwarfism and marked obesity, patients are alive at the ages of 75-78 years, with some having reached even more advanced ages. It is assumed that a major contributing factor is their protection from cancer, a major cause of death in the general population.

Mortality and GH deficiency

DEFF Research Database (Denmark)

Stochholm, Kirstine; Gravholt, Claus Højbjerg; Laursen, Torben

2007-01-01

into childhood onset (CO) and adult onset (AO), discriminated by an age cutoff below or above 18 years at onset of GHD. METHOD: Data on death were identified in national registries. Sex- and cause-specific mortalities were identified in CO and AO GHD when compared with controls. RESULTS: Mortality was increased......OBJECTIVE: To estimate the mortality in Denmark in patients suffering from GH deficiency (GHD). DESIGN: Mortality was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in GHD patients were studied and additional morbidity noted. Patients were divided...... in CO and AO GHD in both genders, when compared with controls. The hazard ratio (HR) for CO males was 8.3 (95% confidence interval (CI) 4.5-15.1) and for females 9.4 (CI 4.6-19.4). For AO males, HR was 1.9 (CI 1.7-2.2) and for females 3.4 (CI 2.9-4.0). We found a significantly higher HR in AO females...

Morbidity and GH deficiency: a nationwide study

DEFF Research Database (Denmark)

Stochholm, K.; Laursen, T.; Green, A.

2008-01-01

identified in the National Patient Registry. Lag time until first admission was used as a measure of morbidity. Patients were divided into childhood onset (CO) and adult onset (AO), discriminated by an age cut-off of 18 years at onset of GHD. Method: Sex- and cause-specific hazard ratios (HRs) in CO and AO......Objective: To estimate morbidity in Denmark in all patients with GH deficiency (GHD). Design: Morbidity was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in the GHD patients were studied and additional morbidity noted. Diagnoses and dates of admissions were...

Changes in bone mineral density, body composition, and lipid metabolism during growth hormone (GH) treatment in children with GH deficiency

NARCIS (Netherlands)

A.M. Boot (Annemieke); M.A. Engels (Melanie); G.J.M. Boerma (Geert); E.P. Krenning (Eric); S.M.P.F. de Muinck Keizer-Schrama (Sabine)

1997-01-01

textabstractAdults with childhood onset GH deficiency (GHD) have reduced bone mass, increased fat mass, and disorders of lipid metabolism. The aim of the present study was to evaluate bone mineral density (BMD), bone metabolism, body composition, and lipid metabolism in

Safety and convenience of once-weekly somapacitan in adult GH deficiency: a 26-week randomized, controlled trial.

Science.gov (United States)

Johannsson, Gudmundur; Feldt-Rasmussen, Ulla; Håkonsson, Ida Holme; Biering, Henrik; Rodien, Patrice; Tahara, Shigeyuki; Toogood, Andrew; Rasmussen, Michael Højby

2018-05-01

Somapacitan is a reversible albumin-binding growth hormone (GH) derivative, developed for once-weekly administration. This study aimed to evaluate the safety of once-weekly somapacitan vs once-daily Norditropin ® . Local tolerability and treatment satisfaction were also assessed. 26-week randomized, controlled phase 3 safety and tolerability trial in six countries (Nbib2382939). Male or female patients aged 18-79 years with adult GH deficiency (AGHD), treated with once-daily GH for ≥6 months, were randomized to once-weekly somapacitan ( n  = 61) or once-daily Norditropin ( n  = 31) administered subcutaneously by pen. Both treatments were dose titrated for 8 weeks to achieve insulin-like growth factor I (IGF-I) standard deviation score (SDS) levels within the normal range, and then administered at a fixed dose. Outcome measures were adverse events (AEs), including injection site reactions; occurrence of anti-somapacitan/anti-GH antibodies and change in treatment satisfaction, assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). Mean IGF-I SDS remained between 0 and 2 SDS throughout the trial in both groups. AEs were mostly mild or moderate and transient in nature. The most common AEs were nasopharyngitis, headache and fatigue in both groups. More than 1500 somapacitan injections were administered and no clinically significant injection site reactions were reported. No anti-somapacitan or anti-GH antibodies were detected. The TSQM-9 score for convenience increased significantly more with somapacitan vs Norditropin ( P  = 0.0171). In this 26-week trial in patients with AGHD, somapacitan was well tolerated and no safety issues were identified. Once-weekly somapacitan was reported to be more convenient than once-daily Norditropin. © 2018 The authors.

Effects of growth hormone replacement therapy on IGF-related parameters and on the pituitary-gonadal axis in GH-deficient males. A double-blind, placebo-controlled crossover study

DEFF Research Database (Denmark)

Juul, A; Andersson, A M; Pedersen, S A

1998-01-01

It has been suggested that growth hormone (GH) may play a regulatory role in male reproductive function. To express full anabolic effect in immature boys testosterone apparently requires the presence of GH. In GH-deficient adults, GH replacement therapy exerts a variety of anabolic actions, some...... study in 13 young males with childhood-onset GH deficiency of which 6 had isolated GH deficiency. GH treatment significantly increased serum levels of total IGF-I from 98 (68) to 323 (126) microg/l, free IGF-I from 0.48 (0.47) to 2.24 (1.66) microg/l, IGFBP-3 from 1,874 (1,178) to 3,520 (778) microg...... in hypogonadal patients substituted with androgens, but GH had no effect on inhibin-B levels. In conclusion, GH replacement therapy in 13 GH-deficient young adult males resulted in significant increases in total and free IGF-I as well as in ALS levels in all patients, but had no significant effect on: (1...

Growth hormone dose regimens in adult GH deficiency: effects on biochemical growth markers and metabolic parameters

DEFF Research Database (Denmark)

Møller, Jens; Jørgensen, Jens Otto Lunde; Laursen, Torben

1993-01-01

Abstract OBJECTIVE: We examined the effects of different doses of GH on insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP-3), body composition, energy expenditure, and various metabolites in GH deficient adults, in order to approach a metabolically appropriate GH dosage in young GH......-I in an age and sex matched control group was 248 +/- 25 micrograms/l. Corresponding serum IGFBP-3 levels also increased from 1860 +/- 239 to 3261 +/- 379, 3762 +/- 434 and 4384 +/- 652 micrograms/l (P = 0.01) respectively. Significant increases in diurnal serum insulin levels after 4 IU/m2 were recorded......, whereas plasma glucose levels remained unchanged. Lipid intermediates increased dose independently during GH administration. GH caused a significant increase in resting energy expenditure, whereas the respiratory exchange ratio was unaltered. Fat mass was increased without GH therapy and decreased during...

Effects of up to 15 years of recombinant human GH (rhGH) replacement on bone metabolism in adults with growth hormone deficiency (GHD): the Leiden Cohort Study.

Science.gov (United States)

Appelman-Dijkstra, Natasha M; Claessen, Kim M J A; Hamdy, Neveen A T; Pereira, Alberto M; Biermasz, Nienke R

2014-11-01

Growth hormone deficiency (GHD) in adulthood may be associated with a decreased bone mineral density (BMD), a decreased bone mineral content (BMC) and an increased fracture risk. Recombinant human GH (rhGH) replacement induces a progressive increase in BMD for up to 5-7 years of treatment. Data on longer follow-up are, however, scarce. Two hundred and thirty-adult GHD patients (mean age 47·1 years, 52·6% female), of whom 88% patients had adult-onset (AO) GHD, receiving rhGH replacement for ≥5 years were included in the study. Most patients had multiple pituitary hormone deficiencies. Bone turnover markers, BMC and BMD and T-scores at the lumbar spine and femoral neck were evaluated at baseline, and after 5, 10 and 15 years of rhGH replacement. In addition, clinical fracture incidence was assessed. Mean lumbar spine BMD, lumbar spine BMC and T-scores gradually increased during the first 10 years of rhGH replacement and remained stable thereafter. Largest effects of rhGH supplementation were found in men. In the small subset of patients using bisphosphonates, use of bisphosphonates did not impact additional beneficial effects in the long term. Low baseline BMD positively affected the change in BMD and BMC over time, but there was a negative effect of high GH dose at 1 year on the change in BMD and BMC over time. Clinical fracture incidence during long-term rhGH replacement was 20.1/1000 py. Fifteen years of rhGH replacement in GHD adults resulted in a sustained increase in BMD values at the lumbar spine, particularly in men, and stabilization of BMD values at the femoral neck. Clinical fracture incidence was suggested not to be increased during long-term rhGH replacement. © 2014 John Wiley & Sons Ltd.

Gene expression of a truncated and the full-length growth hormone (GH) receptor in subcutaneous fat and skeletal muscle in GH-deficient adults

DEFF Research Database (Denmark)

Fisker, Sidse; Kristensen, K; Rosenfalck, A M

2001-01-01

the relationship of circulating GHBP and body composition to GHR and GHRtr gene expression. Eleven adult GH-deficient patients were studied before and after 4 months of GH substitution therapy. Abdominal fat obtained by liposuction and femoral muscle biopsies were taken at baseline and after 4 months. Gene...... expression of GHR and GHRtr in adipose tissue and skeletal muscle was determined and expressed relative to the expression of beta-actin. Gene expression of GHR in abdominal sc adipose tissue was not altered, whereas the expression of GHRtr increased significantly. In skeletal muscle inverse changes were seen...... in the expression of messenger ribonucleic acid (mRNA) levels for the two GH receptor forms: expression of GHR increased significantly, whereas mRNA levels for GHRtr decreased. As expected, body composition changed with reduction of body fat mass after 4 months of GH treatment. Levels of circulating GHBP decreased...

Cardiac manifestations of GH deficiency after treatment for acromegaly: a comparison to patients with biochemical remission and controls

NARCIS (Netherlands)

van der Klaauw, Agatha A.; Bax, Jeroen J.; Bleeker, Gabe B.; Holman, Eduard R.; Delgado, V.; Smit, Johannes W. A.; Romijn, Johannes A.; Pereira, Alberto M.

2008-01-01

Both GH excess and GH deficiency (GHD) lead to specific cardiac pathology. The aim of this study was to evaluate cardiac morphology and function in patients with GHD after treatment for acromegaly. Cross-sectional study. Cardiac parameters were studied by conventional two-dimensional

Transient Ischemic Attack Caused by Iron Deficiency Anemia

Directory of Open Access Journals (Sweden)

Ufuk Emre

2006-02-01

Full Text Available Transient Ischemic Attack Caused by Iron Deficiency Anemia Transient ischemic attacks are episodes of transient focal ischemia involving the brain or brainstem. They are commonly two to thirty minutes in duration and lasting less than 24 hours. Anemia of iron deficiency isn’t frequently cause for transient ischemic attack. It has been reported as a risk factor for childhood ischemic strokes. In the iron deficiency anemia, T‹A may develop as result of hypercoagulable state and increased viscosity that is caused by anemic hypoxia that is result of reduce hemoglobine level, seconder thrombosis and microcytose As iron deficiency anemia has been reported so rarely in adult patients with transient ischemic attacks as a cause, we aimed to discuss the clinical and outcome features of two cases with iron deficiency anemia and transient ischemic attacks in this study. Materials and methods: Routine neurologic examination, biochemical screen, serological tests, vasculitic markers, thyroid function tests, vitamin B 12 level, cranial imaging, vertebral carotid doppler USG examination was conducted in the two patients. Anemia of iron deficiency was found as the only risk factor for TIA and the two patients were treated with replacement of iron and antiagregan therapy. Neurological examination revealed no abnormality through the two years of follow-up. The iron deficiency anemia may be cause of many neurologic problems such a irritability, lethargy, headache, development retardation except from T‹A. In the iron deficiency anemia, early diagnosis and treatment is important

The effect of 30 months of low-dose replacement therapy with recombinant human growth hormone (rhGH) on insulin and C-peptide kinetics, insulin secretion, insulin sensitivity, glucose effectiveness, and body composition in GH-deficient adults

DEFF Research Database (Denmark)

Rosenfalck, A M; Maghsoudi, S; Fisker, S

2000-01-01

The aim of the present study was to evaluate the long-term (30 months) metabolic effects of recombinant human GH (rhGH) given in a mean dose of 6.7 microg/kg x day (= 1.6 IU/day), in 11 patients with adult GH deficiency. Glucose metabolism was evaluated by an oral glucose tolerance test and an iv...... (frequently sampled iv glucose tolerance test) glucose tolerance test, and body composition was estimated by dual-energy x-ray absorptiometry. Treatment with rhGH induced persistent favorable changes in body composition, with a 10% increase in lean body mass (P ... in glucose tolerance, beta-cell response was still inappropriate. Our conclusion is that long-term rhGH-replacement therapy in GH deficiency adults induced a significant deterioration in glucose tolerance, profound changes in kinetics of C-peptide, and insulin and prehepatic insulin secretion, despite...

Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone (GH) dose in adults with severe GH deficiency

NARCIS (Netherlands)

Yuen, Kevin C. J.; Frystyk, Jan; White, Deborah K.; Twickler, Th B.; Koppeschaar, Hans P. F.; Harris, Philip E.; Fryklund, Linda; Murgatroyd, Peter R.; Dunger, David B.

2005-01-01

OBJECTIVE: Untreated GH-deficient adults are predisposed to insulin resistance and excess cardiovascular mortality. We showed previously that short-term treatment with a very low GH dose (LGH) enhanced insulin sensitivity in young healthy adults. The present study was therefore designed to explore

Type I and III procollagen propeptides in growth hormone-deficient patients: effects of increasing doses of GH

DEFF Research Database (Denmark)

Jensen, L T; Jørgensen, J O; Risteli, J

1991-01-01

The effect of increasing doses of growth hormone on collagen synthesis in GH-treated GH-deficient patients was determined in a short-term study. The synthesis of type I and III collagen was estimated by measurements of the carboxyterminal propeptide of type I procollagen and the aminoterminal...... procollagen propeptide increased twice as much as type I procollagen propeptide, by 47 vs 25%, at a GH dose of 6 IU/day compared with 2 IU/day. The differences between the effects on type I and type III collagen may reflect differences in secretion or turn-over rate of collagen in bone and loose connective...

The effect of growth hormone (GH) replacement on muscle strength in patients with GH-deficiency: a meta-analysis.

LENUS (Irish Health Repository)

Widdowson, W Matthew

2012-02-01

CONTEXT\\/OBJECTIVES: GH replacement increases muscle mass and reduces body fat in growth hormone deficiency (GHD) adults. A recent meta-analysis has demonstrated that this improvement in body composition is associated with improved exercise performance. The current meta-analysis was carried out to determine whether high-quality evidence exists to support a beneficial effect of GH replacement on strength. DESIGN\\/METHODS: An extensive Medline search\\/literature review identified eight studies with utilizable, robust data, involving 231 patients in nine cohorts. Previously unpublished data were sought from authors and obtained in two cases. All studies included were randomized, double-blind, placebo-controlled, of parallel or cross-over design and of an average 6.7 months duration. Information was retrieved in uniform format, with data pertaining to patient numbers, study-design, GH-dose, mean age, IGF-I levels and muscle strength measurements (isometric or isokinetic quadriceps strength) recorded. Data were analysed using a fixed-effects model, utilizing continuous data measured on different scales. A summary effect measure (d(s)) was derived for individual strength variables, whereas an overall summary effect was derived from the sum of all studies incorporating different variables; 95% CIs were calculated from the weighted variances of individual study effects. RESULTS: Analysis revealed no significant improvement, neither when all studies were combined (d(s) = +0.01 +\\/- 0.26) nor when measured individually (isometric quadriceps strength, d(s) = +0.02 +\\/- 0.32 and isokinetic quadriceps strength, d(s) = 0.00 +\\/- 0.45). CONCLUSIONS: Evidence from short-term controlled studies fails to support a benefit on muscle strength of GH replacement in GHD patients, which is likely to occur over a longer time-course, as seen in open-label studies.

Comorbidity and cardiovascular risk factors in adult GH deficiency following treatment for Cushing's disease or non-functioning pituitary adenomas during childhood

DEFF Research Database (Denmark)

Ragnarsson, Oskar; Höybye, Charlotte; Jönsson, Peter J

2012-01-01

Cushing's disease (CD) and non-functioning pituitary adenoma (NFPA) are rare in paediatric patients. The aim of this study was to describe long-term consequences in adults with GH deficiency (GHD) treated for CD or NFPA during childhood.......Cushing's disease (CD) and non-functioning pituitary adenoma (NFPA) are rare in paediatric patients. The aim of this study was to describe long-term consequences in adults with GH deficiency (GHD) treated for CD or NFPA during childhood....

Is further evaluation for growth hormone (GH) deficiency necessary in fibromyalgia patients with low serum insulin-like growth factor (IGF)-I levels?

Science.gov (United States)

Yuen, Kevin C J; Bennett, Robert M; Hryciw, Cheryl A; Cook, Marie B; Rhoads, Sharon A; Cook, David M

2007-02-01

Fibromyalgia (FM) is characterized by diffuse pain, fatigue, and sleep disturbances; symptoms that resemble the adult growth hormone (GH) deficiency syndrome. Many FM patients have low serum GH levels, with a hypothesized aetiology of dysregulated GH/insulin-like growth factor (IGF)-I axis. The aim of this study was to assess the GH reserve in FM patients with low serum IGF-I levels using the GH-releasing hormone (GHRH)-arginine test. We retrospectively reviewed the GHRH-arginine data of 77 FM patients with low serum IGF-I levels referred to our tertiary unit over a 4-year period. Of the 77 FM patients, 13 patients (17%) failed the GHRH-arginine test. Further evaluation with pituitary imaging revealed normal pituitary glands (n=7), coincident microadenomas (n=4), empty sella (n=1) and pituitary cyst (n=1), and relevant medical histories such as previous head injury (n=4), Sheehan's syndrome (n=1), and whiplash injury (n=1). In contrast, the remaining 64 patients (83%) that responded to the GHRH-arginine test demonstrated higher peak GH levels compared to age and BMI-matched controls (n=24). Our data shows that a subpopulation of FM patients with low serum IGF-I levels will fail the GHRH-arginine test. We, thus, recommend that the GH reserve of these patients should be evaluated further, as GH replacement may potentially improve the symptomatology of those with true GH deficiency. Additionally, the increased GH response rates to GHRH-arginine stimulation in the majority of FM patients with low serum IGF-I levels further supports the hypothesis of a dysregulated GH/IGF-I axis in the pathophysiology of FM.

GH treatment to final height produces similar height gains in patients with SHOX deficiency and turner syndrome: Results of a multicenter trial

NARCIS (Netherlands)

W.F. Blum (Werner); J.L. Ross (J.); A.G. Zimmermann (Alan); C.A. Quigley (Charmian); C.J. Child (Christopher); G. Kalifa (Gabriel); C.L. Deal (Cheri Lynn); S.L.S. Drop (Stenvert); G. Rappold (G.); G. Cutler (Gordon)

2013-01-01

textabstractContext: Growth impairment in short stature homeobox-containing gene (SHOX) deficiency and Turner syndrome share a similar etiology. Because of the established effect of GH treatment on height in patients with Turner syndrome, we hypothesized that GH therapy would also stimulate growth

Long-term effects of growth hormone (GH) replacement in men with childhood-onset GH deficiency

NARCIS (Netherlands)

ter Maaten, JC; De Boer, H; Kamp, O; Stuurman, L; Van der Veen, EA

Short term GH replacement therapy has been shown to improve body composition and exercise capacity. It is not yet known whether GH replacement remains beneficial over the long term. We assessed the effects of long term GH replacement on body composition, bone mineral density, and cardiac function.

Parentally-adjusted deficit of height as a prognostic factor of the effectiveness of growth hormone (GH) therapy in children with GH deficiency.

Science.gov (United States)

Hilczer, Maciej; Smyczyńska, Joanna; Lewiński, Andrzej

2006-01-01

Parental height is the most important identifiable factor influencing final height (FH) of children with growth hormone (GH) deficiency (GHD), treated with GH. Assessment of FH of patients with GHD--classified into familial short stature (FSS) and non-familial short stature (non-FSS) according to parentally adjusted deficit of height. The analysis comprised 101 patients (76 boys) with childhood-onset GHD. Final height was compared with patients' height before GH therapy, predicted adult height (PAH) and target height (TH). Both GH peak in stimulating tests and height standard deviation score (SDS) before the therapy were significantly lower in non-FSS than in FSS. Target height was significantly lower in FSS than in non-FSS. Parentally-adjusted deficit of height was significantly more profound in non-FSS than in FSS. The prognosis of adult height was very similar in both groups of patients, being significantly worse in non-FSS than in FSS while corrected by TH. The absolute FH was similar in FSS and non-FSS, being, however, significantly lower in non-FSS than in FSS while corrected by TH. Improvement of height was significantly better in non-FSS than in FSS. In both groups, FH SDS was significantly better than height SDS before the therapy (H0SDS). In FSS group, PAH was similar to TH, moreover, FH corresponded to both PAH and TH. In non-FSS group FH was significantly higher than PAH, but both FH and PAH were significantly lower than TH. 1) Growth hormone therapy was more effective in the patients with non-FSS than in those with FSS. 2) Parentally-adjusted deficit of height is an important prognostic factor of GH therapy effectiveness.

The robustness of diagnostic tests for GH deficiency in adults

DEFF Research Database (Denmark)

Andersen, Marianne

2015-01-01

with recombinant human GH. There is, however, an ongoing debate on how to diagnose GHD, especially in adults. A GH response below the cut-off limit of a GH-stimulation test is required in most cases for establishing GHD in adults. No 'gold standard' GH-stimulation test exists, but some GH stimulation tests may...

Overall and cause-specific mortality in GH-deficient adults on GH replacement

DEFF Research Database (Denmark)

Gaillard, Rolf C; Mattsson, Anders F; Akerblad, Ann-Charlotte

2012-01-01

Hypopituitarism is associated with an increased mortality rate but the reasons underlying this have not been fully elucidated. The purpose of this study was to evaluate mortality and associated factors within a large GH-replaced population of hypopituitary patients.......Hypopituitarism is associated with an increased mortality rate but the reasons underlying this have not been fully elucidated. The purpose of this study was to evaluate mortality and associated factors within a large GH-replaced population of hypopituitary patients....

Growth hormone (GH) and atherosclerosis: changes in morphology and function of major arteries during GH treatment.

Science.gov (United States)

Pfeifer, M; Verhovec, R; Zizek, B

1999-04-01

Patients with hypopituitarism have increased carotid artery intima-media thickness and reduced arterial distensibility. The effect of 2 years of growth hormone (GH) replacement therapy on these parameters was studied in 11 GH-deficient men (age range, 24-49 years) with hypopituitarism and compared with 12 healthy, age-matched men with no evidence of pituitary or vascular disease. Before treatment the intima-media of the common carotid arteries and the carotid bifurcations were significantly thicker in patients (P < 0.001) than in the control group. Treatment with GH normalized the intima-media thickness of the common carotid artery within 6 months and of the carotid bifurcation within 3 months. The changes in intima-media thickness of the carotid artery were negatively correlated with changes in serum levels of insulin-like growth factor I during treatment. There was a significant improvement in flow-mediated, endothelium-dependent dilation of the brachial artery at 3 months, which was sustained at 6, 18 and 24 months of GH treatment (P < 0.05). Thus, GH replacement therapy in GH-deficient men reverses early morphological and functional atherosclerotic changes in major arteries, and may reduce rates of vascular morbidity and mortality.

Longitudinal behavior of autoimmune GH deficiency: from childhood to transition age.

Science.gov (United States)

De Bellis, Annamaria; Bellastella, Giuseppe; Maiorino, Maria Ida; Aitella, Ernesto; Lucci, Emma; Cozzolino, Domenico; Bellastella, Antonio; Bizzarro, Antonio; Giugliano, Dario; Esposito, Katherine

2016-03-01

Some cases of apparently idiopathic GH deficiency (GHD) may be caused by pituitary autoimmunity. To study the variations in pituitary function and antipituitary antibodies (APA) from childhood to transition age in patients with apparently idiopathic GHD. We conducted a longitudinal study. Pituitary function and APA detection by immunofluorescence were investigated in 24 childhood patients with isolated GHD before starting recombinant GH therapy and after the stopping of this therapy in transition age. Sera of patients positive for APA were processed by double immunofluorescence to identify their pituitary target. At diagnosis, 16 out of 24 patients were APA positive targeting only somatotrophs (group 1), while the remaining eight were APA negative (group 2). When retested off therapy, 12 out of 16 patients in group 1 persisted being APA positive, while the remaining four became negative with recovery of pituitary function. All patients in group 2 persisted being APA negative but still showing GHD. Of the 12 patients persistently APA positive, eight with confirmed GHD showed APA still targeting somatotrophs, whereas four showed APA targeting only gonadotrophs associated with isolated hypogonadotropic hypogonadism (HH). Patients with APA at middle but not at high titer in childhood may show a remission of autoimmune GHD in childhood after GH replacement therapy. As APA may shift their target in transition period, an early characterization of APA by double immunofluorescence is advisable in APA positive GHD patients showing delayed puberty, to allow an early diagnosis and an appropriate therapy, thus preventing the progression toward HH. © 2016 European Society of Endocrinology.

Mutation of the SHP-2 binding site in growth hormone (GH) receptor prolongs GH-promoted tyrosyl phosphorylation of GH receptor, JAK2, and STAT5B

DEFF Research Database (Denmark)

Stofega, M R; Herrington, J; Billestrup, Nils

2000-01-01

phosphorylation. Consistent with the effects on STAT5B phosphorylation, tyrosine-to-phenylalanine mutation of tyrosine 595 prolongs the duration of tyrosyl phosphorylation of GHR and JAK2. These data suggest that tyrosine 595 is a major site of interaction of GHR with SHP-2, and that GHR-bound SHP-2 negatively......Binding of GH to GH receptor (GHR) rapidly and transiently activates multiple signal transduction pathways that contribute to the growth-promoting and metabolic effects of GH. While the events that initiate GH signal transduction, such as activation of the Janus tyrosine kinase JAK2, are beginning...

Growth hormone administration stimulates energy expenditure and extrathyroidal conversion of thyroxine to triiodothyronine in a dose-dependent manner and suppresses circadian thyrotrophin levels: studies in GH-deficient adults

DEFF Research Database (Denmark)

Laursen, Torben; Jørgensen, Jens Otto Lunde; Møller, Jens

1994-01-01

. CONCLUSIONS: GH administration stimulated peripheral T4 to T3 conversion in a dose-dependent manner. Serum T3 levels were subnormal despite T4 substitution when the patients were off GH but normalized with GH therapy. Energy expenditure increased with GH and correlated with free T3 levels. GH caused......Abstract OBJECTIVE: The impact of exogenous GH on thyroid function remains controversial although most data add support to a stimulation of peripheral T4 to T3 conversion. For further elucidation we evaluated iodothyronine and circadian TSH levels in GH-deficient patients as part of a GH dose...... without GH, whereas GH therapy significantly suppressed the TSH levels and blunted the circadian rhythm (mean TSH levels (mU/l) 0.546 +/- 0.246 (no GH) vs 0.066 +/- 0.031 (2 IU GH) (P

Dexamethasone and BCAA Failed to Modulate Muscle Mass and mTOR Signaling in GH-Deficient Rats.

Science.gov (United States)

Nishida, Hikaru; Ikegami, Ayaka; Kaneko, Chiaki; Kakuma, Hitomi; Nishi, Hisano; Tanaka, Noriko; Aoyama, Michiko; Usami, Makoto; Okimura, Yasuhiko

2015-01-01

Branched-chain amino acids (BCAAs) and IGF-I, the secretion of which is stimulated by growth hormone (GH), prevent muscle atrophy. mTOR plays a pivotal role in the protective actions of BCAA and IGF-1. The pathway by which BCAA activates mTOR is different from that of IGF-1, which suggests that BCAA and GH work independently. We tried to examine whether BCAA exerts a protective effect against dexamethasone (Dex)-induced muscle atrophy independently of GH using GH-deficient spontaneous dwarf rats (SDRs). Unexpectedly, Dex did not induce muscle atrophy assessed by the measurement of cross-sectional area (CSA) of the muscle fibers and did not increase atrogin-1, MuRF1 and REDD1 expressions, which are activated during protein degradation. Glucocorticoid (GR) mRNA levels were higher in SDRs compared to GH-treated SDRs, indicating that the low expression of GR is not the reason of the defect of Dex's action in SDRs. BCAA did not stimulate the phosphorylation of p70S6K or 4E-BP1, which stimulate protein synthesis. BCAA did not decrease the mRNA level of atrogin-1 or MuRF1. These findings suggested that Dex failed to modulate muscle mass and that BCAA was unable to activate mTOR in SDRs because these phosphorylations of p70S6K and 4E-BP1 and the reductions of these mRNAs are regulated by mTOR. In contrast, after GH supplementation, these responses to Dex were normalized and muscle fiber CSA was decreased by Dex. BCAA prevented the Dex-induced decrease in CSA. BCAA increased the phosphorylation of p70S6K and decreased the Dex-induced elevations of atrogin-1 and Bnip3 mRNAs. However, the amount of mTORC1 components including mTOR was not decreased in the SDRs compared to the normal rats. These findings suggest that GH increases mTORC1 activity but not its content to recover the action of BCAA in SDRs and that GH is required for actions of Dex and BCAA in muscles.

Dexamethasone and BCAA Failed to Modulate Muscle Mass and mTOR Signaling in GH-Deficient Rats.

Directory of Open Access Journals (Sweden)

Hikaru Nishida

Full Text Available Branched-chain amino acids (BCAAs and IGF-I, the secretion of which is stimulated by growth hormone (GH, prevent muscle atrophy. mTOR plays a pivotal role in the protective actions of BCAA and IGF-1. The pathway by which BCAA activates mTOR is different from that of IGF-1, which suggests that BCAA and GH work independently. We tried to examine whether BCAA exerts a protective effect against dexamethasone (Dex-induced muscle atrophy independently of GH using GH-deficient spontaneous dwarf rats (SDRs. Unexpectedly, Dex did not induce muscle atrophy assessed by the measurement of cross-sectional area (CSA of the muscle fibers and did not increase atrogin-1, MuRF1 and REDD1 expressions, which are activated during protein degradation. Glucocorticoid (GR mRNA levels were higher in SDRs compared to GH-treated SDRs, indicating that the low expression of GR is not the reason of the defect of Dex's action in SDRs. BCAA did not stimulate the phosphorylation of p70S6K or 4E-BP1, which stimulate protein synthesis. BCAA did not decrease the mRNA level of atrogin-1 or MuRF1. These findings suggested that Dex failed to modulate muscle mass and that BCAA was unable to activate mTOR in SDRs because these phosphorylations of p70S6K and 4E-BP1 and the reductions of these mRNAs are regulated by mTOR. In contrast, after GH supplementation, these responses to Dex were normalized and muscle fiber CSA was decreased by Dex. BCAA prevented the Dex-induced decrease in CSA. BCAA increased the phosphorylation of p70S6K and decreased the Dex-induced elevations of atrogin-1 and Bnip3 mRNAs. However, the amount of mTORC1 components including mTOR was not decreased in the SDRs compared to the normal rats. These findings suggest that GH increases mTORC1 activity but not its content to recover the action of BCAA in SDRs and that GH is required for actions of Dex and BCAA in muscles.

The Kenny syndrome, a rare type of growth deficiency with tubular stenosis, transient hypoparathyroidism and anomalies of refraction.

Science.gov (United States)

Majewski, F; Rosendahl, W; Ranke, M; Nolte, K

1981-03-01

One family (3 cases) with the Kenny syndrome and a second family (3 cases) with features of Kenny syndrome but lacking medullary stenosis are reported. The main symptoms in both families are proportionate dwarfism, cortical thickening of tubular bones, variable anomalies of the calvaria, anemia, transient hypoparathyroidism and variable ocular anomalies. The latter include microphthalmia, and moderate-to-severe myopia or hyperopia. In the first family there was medullary stenosis of most tubular bones. In the second family two cases exhibited mild-to-moderate cortical thickening of tubular bones, but absent or mild medullary stenosis. Possible variability of the Kenny syndrome is discussed. Endocrine studies failed to demonstrate any permanent disturbance of parathormone or calcitonin metabolism, or GH deficiency. Pathogenesis remains unclear. Autosomal dominant inheritance seems to be likely.

Fifteen years of GH replacement improves body composition and cardiovascular risk factors.

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Elbornsson, Mariam; Götherström, Galina; Bosæus, Ingvar; Bengtsson, Bengt-Åke; Johannsson, Gudmundur; Svensson, Johan

2013-05-01

Few studies have determined the effects of more than 5-10 years of GH replacement in adults on body composition and cardiovascular risk factors. In this prospective, single-center, open-label study, the effects of 15 years of GH replacement on body composition and cardiovascular risk factors were determined in 156 hypopituitary adults (93 men) with adult-onset GH deficiency (GHD). Mean age was 50.5 (range 22-74) years at study start. Body composition was measured using dual-energy X-ray absorptiometry. The mean initial GH dose of 0.55 (S.E.M. 0.03) mg/day was gradually lowered to 0.40 (0.01) mg/day after 15 years. The mean serum IGF1 SDS increased from -1.53 (0.10) at baseline to 0.74 (0.13) at study end (Plevel at study end (Pbody fat (BF) started to increase and had returned to the baseline level after 15 years. Serum levels of total cholesterol and LDL-cholesterol decreased and serum HDL-cholesterol level increased. Fasting plasma glucose increased from 4.4 (0.1) at baseline to 4.8 (0.1) mmol/l at study end (P<0.001). However, blood HbA1c decreased from 5.0 (0.1) to 4.6 (0.1) % (P<0.001). Fifteen-year GH replacement in GHD adults induced a transient decrease in BF and sustained improvements of LST and serum lipid profile. Fasting plasma glucose increased whereas blood HbA1c was reduced.

Novel Splicing Mutation in B3GAT3 Associated with Short Stature, GH Deficiency, Hypoglycaemia, Developmental Delay, and Multiple Congenital Anomalies

Directory of Open Access Journals (Sweden)

Samuel Bloor

2017-01-01

Full Text Available B3GAT3, encoding β-1,3-glucuronyltransferase 3, has an important role in proteoglycan biosynthesis. Homozygous B3GAT3 mutations have been associated with short stature, skeletal deformities, and congenital heart defects. We describe for the first time a novel heterozygous splice site mutation in B3GAT3 contributing to severe short stature, growth hormone (GH deficiency, recurrent ketotic hypoglycaemia, facial dysmorphism, and congenital heart defects. A female infant, born at 34 weeks’ gestation to nonconsanguineous Caucasian parents with a birth weight of 1.9 kg, was noted to have cloacal abnormality, ventricular septal defect, pulmonary stenosis, and congenital sensorineural deafness. At 4 years of age, she was diagnosed with GH deficiency due to her short stature (height G in the invariant “GT” splice donor site was identified. This variant is considered to be pathogenic as it decreases the splicing efficiency in the mRNA.

Baseline characteristics and response to 2 years of growth hormone (GH) replacement of hypopituitary patients with GH deficiency due to adult-onset craniopharyngioma in comparison with patients with nonfunctioning pituitary adenoma: data from KIMS (Pfizer International Metabolic Database).

Science.gov (United States)

Verhelst, Johan; Kendall-Taylor, Pat; Erfurth, Eva Marie; Price, David Anthony; Geffner, Mitchell; Koltowska-Häggström, Maria; Jönsson, Peter J; Wilton, Patrick; Abs, Roger

2005-08-01

In epidemiological studies, hypopituitary adults show increased mortality compared with population controls. Patients with hypopituitarism caused by a craniopharyngioma (CP) and/or its treatment have a higher mortality than patients with other etiologies, such as a nonfunctioning pituitary adenoma (NFPA). To analyze this difference, we used the KIMS database (Pfizer International Metabolic Database) comparing CP and NFPA patients in terms of baseline characteristics and responses to GH replacement. Baseline characteristics were studied in 351 CP patients (189 men and 162 women; mean age, 42.5 yr) and compared with 370 NFPA patients, matched for age and sex (185 men and 185 women; mean age, 42.5 yr). The effects of 2 yr of GH replacement were analyzed in a subgroup of 183 CP and 209 NFPA patients. At baseline, both CP and NFPA patients had characteristic features of GH deficiency, with low serum IGF-I, increased body fat, dyslipidemia, and reduced quality of life. Male CP patients were significantly more obese (30.0 vs. 28.2 kg/m2; P = 0.0003) compared with NFPA patients, had a higher waist/hip ratio (P = 0.004), higher triglycerides (P = 0.003), and lower high-density lipoprotein cholesterol (P = 0.03). Similar, but much smaller, differences were seen in female CP compared with NFPA patients, only reaching significance for waist/hip ratio (P = 0.05) and triglycerides (P = 0.0004). CP patients had more often undergone surgery by the transcranial route (68.8% vs. 30.9%; P NFPA patients (58.7% vs. 19.8%; P NFPA patients. After 2 yr of GH replacement therapy, similar significant improvements were evident in both groups in fat-free mass, total and low-density lipoprotein cholesterol, and Quality-of-Life-Assessment in GH Deficient Adults score compared with baseline. In contrast to NFPA patients, CP patients had no significant decrease in body fat with GH therapy. In the KIMS database, patients with CP have more often undergone surgery by the transcranial route than

Approach to testing growth hormone (GH) secretion in obese subjects.

Science.gov (United States)

Popovic, Vera

2013-05-01

Identification of adults with GH deficiency (GHD) is challenging because clinical features of adult GHD are not distinctive and because clinical suspicion must be confirmed by biochemical tests. Adults are selected for testing for adult GHD if they have a high pretest probability of GHD, ie, if they have hypothalamic-pituitary disease, if they have received cranial irradiation or central nervous system tumor treatment, or if they survived traumatic brain injury or subarachnoid hemorrhage. Testing should only be carried out if a decision has already been made that if deficiency is found it will be treated. There are many pharmacological GH stimulation tests for the diagnosis of GHD; however, none fulfill the requirements for an ideal test having high discriminatory power; being reproducible, safe, convenient, and economical; and not being dependent on confounding factors such as age, gender, nutritional status, and in particular obesity. In obesity, GH secretion is reduced, GH clearance is enhanced, and stimulated GH secretion is reduced, causing a false-positive result. This functional hyposomatotropism in obesity is fully reversed by weight loss. In conclusion, GH stimulation tests should be avoided in obese subjects with very low pretest probability.

Bioavailability and bioactivity of three different doses of nasal growth hormone (GH) administered to GH-deficient patients

DEFF Research Database (Denmark)

Laursen, Torben; Grandjean, Birgitte; Jørgensen, Jens Otto Lunde

1996-01-01

different occasions. On three occasions GH was administered intranasally in doses of 0.05, 0.10 and 0.20 IU/kg, using didecanoyl-L-alpha-phosphatidylcholine as an enhancer. On the other two occasions the patients received an sc injection (0.10 IU/kg) and an i.v. injection (0.015 IU/kg) of GH, respectively....... The absolute bioavailability of GH following s.c. relative to i.v. administration was 49.5%. The bioavailabilities of the nasal doses were: 7.8% (0.05 IU). 8.9% (0.10 IU) and 3.8% (0.20 IU). Serum insulin-like growth factor I (IGF-I) levels increased significantly after s.c. administration only. Mean levels...... of the i.v. (p insulin and blood glucose (p

Adherence in children with growth hormone deficiency treated with r-hGH and the easypod™ device.

Science.gov (United States)

Loche, S; Salerno, M; Garofalo, P; Cardinale, G M; Licenziati, M R; Citro, G; Caruso Nicoletti, M; Cappa, M; Longobardi, S; Maghnie, M; Perrone, R

2016-12-01

Poor adherence to recombinant human growth hormone (r-hGH) therapy is associated with reduced growth velocity in children with growth hormone deficiency (GHD). This twelve-month observational study was to assess adherence in r-hGH patients treated with the easypod ™ , an electronic, fully automated injection device designed to track the time, date and dose administered. Ninety-seven prepubertal patients receiving r-hGH therapy were included in the study from ten Italian clinical sites and 88 completed the study. To avoid possible confounding effects, only GHD patients (79/88; 89.7 % of the overall study population) were considered in the final analysis. The primary endpoint-adherence to treatment-was calculated as the proportion of injections correctly administered during the observational period out of the expected total number of injections. The relevant information, tracked by the easypod ™ , was collected at months 6 (V1) and 12 (V2) after baseline (V0). At study termination, adherence data were partially available from 16 patients and fully available from 53 patients. As secondary endpoints, serum IGF-1 levels, fasting serum glucose and insulin levels and key anthropometric characteristics (height, waist circumference and BMI) were also determined. The easypod ™ data showed that 56.7 % of the patients were considered to be fully (≥92 %) adherent to their treatment throughout the period V0-V2. Treatment improved stature, significantly increased IGF-1 and produced a non-significant increase in blood glucose and insulin levels. The injection-recording system and other characteristics of easypod ™ could enhance the ability of physicians to monitor adherence to r-hGH treatment.

Growth hormone deficiency and hyperthermia during exercise

DEFF Research Database (Denmark)

Juul, A; Hjortskov, N; Jepsen, Leif

1995-01-01

Sweat secretion is often disturbed in patients with GH secretory disorders. Hyperhidrosis is a classic feature of acromegaly, and it has recently been shown that GH-deficient patients exhibit decreased sweating capacity after pilocarpine stimulation of the skin. Thus, patients with GH-deficiency ...

Induction of chronic growth hormone deficiency by anti-GH serum

Science.gov (United States)

Grindeland, R. E.; Smith, A. T.; Ellis, S.; Evans, E. S.

1974-01-01

The observations reported indicate that the growth rate of neonatal rats can be specifically inhibited for at least 78 days following the administration of antisera against growth hormone (GH) for only four days after birth. The inhibition can be correlated with a marked deficit of tibial growth promoting activity in the pituitary but not with the plasma concentrations of immuno-reactive GH.

Duchenne muscular dystrophy with associated growth hormone deficiency

International Nuclear Information System (INIS)

Ghafoor, T.; Mahmood, A.; Shams, S.

2003-01-01

A patient with duchenne muscular dystrophy (DMD) and growth hormone (GH) deficiency is described who had no clinical evidence of muscular weakness before initiation of GH replacement therapy. Treatment with human GH resulted in appearance of symptoms of easy fatigability and muscle weakness. Thorough investigations including serum creating phosphokinase (CK) levels in recommended in every patient with GH deficiency before starting GH replacement therapy. (author)

Comparison of two dose regimens of growth hormone (GH) with different target IGF-1 levels on glucose metabolism, lipid profile, cardiovascular function and anthropometric parameters in gh-deficient adults.

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Cenci, Maria Claudia Peixoto; Soares, Débora Vieira; Spina, Luciana Diniz Carneiro; Brasil, Rosane Resende de Lima Oliveira; Lobo, Priscila Marise; Michmacher, Eduardo; Vaisman, Mario; Boguszewski, Cesar Luiz; Conceição, Flávia Lúcia

2012-01-01

To compare the effects of two regimens of GH therapy with different target IGF-1 levels on anthropometric parameters, glucose metabolism, lipid profile and cardiac function in adults with GH deficiency (GHD). Retrospective analysis of 14 GHD adults from Clementino Fraga Filho University Hospital, Rio de Janeiro, Brazil, who were treated with a GH regimen aimed at maintaining serum IGF-1 levels between the median and upper reference limit (high dose group - HDGH) and 18 GHD adults from Federal University Hospital, Curitiba, Brazil, who received a fixed GH dose of 0.2mg/day in the first year of treatment, followed by titration to maintain serum IGF-1 levels between the median and lower reference limit (low dose group - LDGH). All patients were followed for 2 years with analysis of anthropometric parameters, serum levels of IGF-1, glucose, insulin, HOMA-IR, lipid profile, and transthoracic echocardiography. Changes on weight, BMI and waist circumference were similar between the two groups. Insulin levels increased and HOMA-IR worsened in the LDGH group at 1year and improved thereafter. Total cholesterol and triglycerides did not change with therapy. LDL cholesterol reduced in both groups, while HDL-cholesterol significantly increased only in the HDGH group (p=0.007 vs LDGH). No significant variations on echocardiographic parameters were observed. The HDGH and LDGH regimens resulted in similar changes on anthropometric, echocardiographic, glucose and lipid parameters in GHD adults, except for increase in HDL cholesterol that was only observed in the HDGH regimen. Copyright © 2012 Elsevier Ltd. All rights reserved.

Growth hormone replacement does not elevate albuminuria in GH-deficient adults

NARCIS (Netherlands)

Beentjes, JAM; Dullaart, RPF

2002-01-01

Minor elevations in urinary albumin excretion rate (Ualb.V) are likely to be associated with renal function loss and increased cardiovascular risk. Since urinary albumin excretion is affected by the growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis, we evaluated the effect of 6 months GH

The role of GH receptor tyrosine phosphorylation in Stat5 activation

DEFF Research Database (Denmark)

Hansen, J A; Hansen, L H; Wang, X

1997-01-01

Stimulation of GH receptors leads to rapid activation of Jak2 kinase and subsequent tyrosine phosphorylation of the GH receptor. Three specific tyrosines located in the C-terminal domain of the GH receptor have been identified as being involved in GH-stimulated transcription of the Spi 2.1 promoter....... Mutated GH receptors lacking all but one of these three tyrosines are able to mediate a transcriptional response when transiently transfected into CHO cells together with a Spi 2.1 promoter/luciferase construct. Similarly, these GH receptors were found to be able to mediate activation of Stat5 DNA......-binding activity, whereas the GH receptor mutant lacking all intracellular tyrosines was not. Synthetic tyrosine phosphorylated peptides corresponding to the GH receptor sequence around the three tyrosines inhibited Stat5 DNA-binding activity while their non-phosphorylated counterparts were ineffective. Tyrosine...

Vasoprotective effects of life span-extending peripubertal GH replacement in Lewis dwarf rats.

Science.gov (United States)

Ungvari, Zoltan; Gautam, Tripti; Koncz, Peter; Henthorn, Jim C; Pinto, John T; Ballabh, Praveen; Yan, Han; Mitschelen, Matthew; Farley, Julie; Sonntag, William E; Csiszar, Anna

2010-11-01

In humans, growth hormone deficiency (GHD) and low circulating levels of insulin-like growth factor 1 (IGF-1) significantly increase the risk for cerebrovascular disease. Genetic growth hormone (GH)/IGF-1 deficiency in Lewis dwarf rats significantly increases the incidence of late-life strokes, similar to the effects of GHD in elderly humans. Peripubertal treatment of Lewis dwarf rats with GH delays the occurrence of late-life stroke, which results in a significant extension of life span. The present study was designed to characterize the vascular effects of life span-extending peripubertal GH replacement in Lewis dwarf rats. Here, we report, based on measurements of dihydroethidium fluorescence, tissue isoprostane, GSH, and ascorbate content, that peripubertal GH/IGF-1 deficiency in Lewis dwarf rats increases vascular oxidative stress, which is prevented by GH replacement. Peripubertal GHD did not alter superoxide dismutase or catalase activities in the aorta nor the expression of Cu-Zn-SOD, Mn-SOD, and catalase in the cerebral arteries of dwarf rats. In contrast, cerebrovascular expression of glutathione peroxidase 1 was significantly decreased in dwarf vessels, and this effect was reversed by GH treatment. Peripubertal GHD significantly decreases expression of the Nrf2 target genes NQO1 and GCLC in the cerebral arteries, whereas it does not affect expression and activity of endothelial nitric oxide synthase and vascular expression of IGF-1, IGF-binding proteins, and inflammatory markers (tumor necrosis factor alpha, interluekin-6, interluekin-1β, inducible nitric oxide synthase, intercellular adhesion molecule 1, and monocyte chemotactic protein-1). In conclusion, peripubertal GH/IGF-1 deficiency confers pro-oxidative cellular effects, which likely promote an adverse functional and structural phenotype in the vasculature, and results in accelerated vascular impairments later in life.

Extensive expertise in endocrinology: UK stance on adult GH replacement: the economist vs the endocrinologist.

Science.gov (United States)

Shalet, S M

2013-10-01

In the UK, through the use of a forced economic model, endocrinologists are in the curious position of offering GH replacement to some patients with severe GH deficiency (GHD) but withholding it from other patients with even more severe GHD. This approach is counter-intuitive to endocrine practice in treating endocrine deficiency states. For all other endocrine deficiencies, one would opt for treating those with the most severe biochemical evidence of deficiency first. If this endocrine approach was applied to adult GH replacement in an era of rationing, one would start with the GHD patients with a pathologically low IGF1 level. Given that the prevalence of subnormal IGF1 levels in a GHD population is age-dependent, this would result in GH replacement being offered to more young adult onset (AO) GHD and childhood onset GHD adults, and less often to middle-aged and elderly AO GHD adults. This in itself has the added advantage that the skeletal benefits appear more real in the former cohort of patients.

Isolated growth hormone deficiency in two siblings because of paternal mosaicism for a mutation in the GH1 gene.

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Tsubahara, Mayuko; Hayashi, Yoshitaka; Niijima, Shin-ichi; Yamamoto, Michiyo; Kamijo, Takashi; Murata, Yoshiharu; Haruna, Hidenori; Okumura, Akihisa; Shimizu, Toshiaki

2012-03-01

  Mutations in the GH1 gene have been identified in patients with isolated growth hormone deficiency (IGHD). Mutations causing aberrant splicing of exon 3 of GH1 that have been identified in IGHD are inherited in an autosomal dominant manner, whereas other mutations in GH1 that have been identified in IGHD are inherited in an autosomal recessive manner.   Two siblings born from nonconsanguineous healthy parents exhibited IGHD. To elucidate the cause, GH1 in all family members was analysed.   Two novel mutations in GH1, a point mutation in intron 3 and a 16-bp deletion in exon 3, were identified by sequence analyses. The intronic mutation was present in both siblings and was predicted to cause aberrant splicing. The deletion was present in one of the siblings as well as the mother with normal stature and was predicted to cause rapid degradation of mRNA through nonsense-mediated mRNA decay. The point mutation was not identified in the parents' peripheral blood DNA; however, it was detected in the DNA extracted from the father's sperms. As a trace of the mutant allele was detected in the peripheral blood of the father using PCR-RFLP, the mutation is likely to have occurred de novo at an early developmental stage before differentiation of somatic cells and germline cells.   This is the first report of mosaicism for a mutation in GH1 in a family with IGHD. It is clear that the intronic mutation plays a dominant role in the pathogenesis of IGHD in this family, as one of the siblings who had only the point mutation was affected. On the other hand, the other sibling was a compound heterozygote for the point mutation and the 16-bp deletion and it may be arguable whether IGHD in this patient should be regarded as autosomal dominant or recessive. © 2012 Blackwell Publishing Ltd.

Effects of growth hormone and insulin-like growth factor 1 deficiency on ageing and longevity.

Science.gov (United States)

Laron, Zvi

2002-01-01

Present knowledge on the effects of growth hormone (GH)/insulin-like growth hormone (IGF)1 deficiency on ageing and lifespan are reviewed. Evidence is presented that isolated GH deficiency (IGHD), multiple pituitary hormone deficiencies (MPHD) including GH, as well as primary IGE1 deficiency (GH resistance, Laron syndrome) present signs of early ageing such as thin and wrinkled skin, obesity, hyperglycemia and osteoporosis. These changes do not seem to affect the lifespan, as patients reach old age. Animal models of genetic MPHD (Ames and Snell mice) and GH receptor knockout mice (primary IGF1 deficiency) also have a statistically significant higher longevity compared to normal controls. On the contrary, mice transgenic for GH and acromegalic patients secreting large amounts of GH have premature death. In conclusion longstanding GH/IGF1 deficiency affects several parameters of the ageing process without impairing lifespan, and as shown in animal models prolongs longevity. In contrast high GH/IGF1 levels accelerate death.

Production and characterisation of glycoside hydrolases from GH3, GH5, GH10, GH11 and GH61 for chemo-enzymatic synthesis of xylo- and mannooligosaccharides

DEFF Research Database (Denmark)

Dilokpimol, Adiphol

Produktion og karakterisering af glykosid hydrolaser fro GH3, GH5, GH10, GH11 og GH61 til chemo-enzymatisk syntese af xylo- og mannooligosakkarider Biprodukter fra hydrolyse af plantecellevægge er kilder til oligosakkarider, som potentielt kan fungere som prebiotika ved at stimulere væksten af...... omfatter karakterisering af de producerede enzymer samt cDNA kloning af formodet GH61 endo Produktion og karakterisering af glykosid hydrolaser fro GH3, GH5, GH10, GH11 og GH61 til chemo-enzymatisk syntese af xylo- og mannooligosakkarider Biprodukter fra hydrolyse af plantecellevægge er kilder til...

Hypothalamic growth hormone releasing factor deficiency following cranial irradiation

International Nuclear Information System (INIS)

Ahmed, S.R.; Shalet, S.M.

1984-01-01

The effect of synthetic human pancreatic tumour GH releasing factor (hp GRF1-44) on GH release has been studied in 10 patients with radiation-induced GH deficiency and four normal subjects. All 10 patients showed subnormal GH responses to both an ITT (median peak GH 3.2 mU/1) and to arginine stimulation (median peak GH 2.9 mU/1), although the remainder of pituitary function was intact. Following an acute intravenous bolus (100 μg) of hp GRF1-44, there was no GH response in two patients and a subnormal but definite GH response in a further four. The remaining four patients showed a significant GH response (median peak GH level 29 mU/1; range 22-57 mU/1) to hp GRF1-44, similar in magnitude and timing to that seen in th four normals. This strongly suggests that in these four subjects, the discrepancy in GH responses to hp GRF1-44, ITT and to arginine was a result of radiation-induced hypothalamic damage leading to a deficiency of endogenous GRF. The availability of synthetic hp GRF capable of stimulating GH secretion means that the distinction between hypothalamic and pituitary causes of GH deficiency will be of considerable therapeutic importance in the future. (author)

Long-Term Follow-up of a Case with Proprotein Convertase 1/3 Deficiency: Transient Diabetes Mellitus with Intervening Diabetic Ketoacidosis During Growth Hormone Therapy.

Science.gov (United States)

Gönç, E. Nazlı; Özön, Alev; Alikaşifoğlu, Ayfer; Kandemir, Nurgün

2017-09-01

Proprotein convertase 1/3 (PC1/3) deficiency is a very rare disease characterized by severe intractable diarrhea in the first years of life, followed by obesity and several hormonal deficiencies later. Diabetes mellitus requiring insulin treatment and diabetic ketoacidosis have not been reported in this disorder. We herein present a girl with PC1/3 deficiency who has been followed from birth to 17 years of age. She developed deficiencies of all pituitary hormones over time as well as diabetes mellitus while receiving growth hormone (GH) therapy. She was complicated with diabetic ketoacidosis during dietary management of diabetes mellitus, thus insulin treatment was initiated. Insulin requirement to regulate hyperglycemia was short-lived. Repeat oral glucose tolerance test five years later was normal. The findings of this patient show that diabetes mellitus can develop at any time during follow-up of cases with proportein convertase 1/3 deficiency especially under GH therapy.

Do IGF-I concentrations better reflect growth hormone (GH action in children with short stature than the results of GH stimulating tests? Evidence from the simultaneous assessment of thyroid function

Directory of Open Access Journals (Sweden)

Smyczyńska Joanna

2011-01-01

Full Text Available Abstract Background The diagnosis of growth hormone (GH deficiency (GHD in short children seems unquestionable when both GH peak in stimulating tests (GHST and IGF-I concentration are decreased. However, the discrepancies between the results of GHST and IGF-I secretion are observed. It seems purposeful to determine the significance of GHST and IGF-I assessment in diagnosing GHD. The relationship between GH secretion and thyroid function, as well as GH influence on the peripheral thyroxine (T4 to triiodothyronine (T3 deiodination, mediated by IGF-I, were identified. Thus, clear differences in thyroid function between GH-deficient and non-GH-deficient subjects should exist. Methods Analysis comprised 800 children (541 boys, age 11.6 ± 3.1 years (mean ± SD, with short stature, in whom two (2 standard GHST (with clonidine and with glucagon were performed and IGF-I, free T4 (FT4, free T3 (FT3 and TSH serum concentrations were assessed. The patients were qualified to the following groups: GHD - decreased GH peak in GHST and IGF-I SDS (n = 81, ISS - normal GH peak and IGF-I SDS (n = 347, low GH - normal IGF-I SDS, and decreased GH peak (n = 212, low IGF - decreased IGF-I SDS, and normal GH peak (n = 160. The relationships among the results of particular tests were evaluated. Results In the groups with decreased IGF-I concentrations (GHD Group and low IGF Group, the more severe deficit of height was observed, together with higher TSH and FT4 but lower FT3 levels than in groups with normal IGF-I concentrations (ISS Group and low GH Group, independently of the results of GHST. TSH, FT4 and FT3 concentrations were - respectively - similar in two groups with decreased IGF-I secretion, as well as in two groups with normal IGF-I levels. Significant correlations were found between patients' height SDS and IGF-I SDS, between FT3 and IGF-I SDS (positive, and between FT4 and IGF-I SDS (negative, with no correlation between GH peak and any of the parameters

Reduced recruitment and survival of primordial and growing follicles in GH receptor-deficient mice

NARCIS (Netherlands)

Slot, K.A.; Kastelijn, J.; Bachelot, A.; Kelly, P.A.; Binart, N.; Teerds, K.J.

2006-01-01

GH influences female fertility. The goal of the present study was to obtain more insight into the effect of loss of GH signalling, as observed in humans suffering from Laron syndrome, on ovarian function. Therefore, serial paraffin sections of ovaries of untreated and IGF-I-treated female GH

Association between l-thyroxine treatment, GH deficiency, and radiological vertebral fractures in patients with adult-onset hypopituitarism.

Science.gov (United States)

Mazziotti, G; Mormando, M; Cristiano, A; Bianchi, A; Porcelli, T; Giampietro, A; Maffezzoni, F; Serra, V; De Marinis, L; Giustina, A

2014-06-01

In this study, we aimed at evaluating the association between radiological vertebral fractures and levo-thyroxine (l-T4) replacement doses in adult patients with hypopituitarism. Cross-sectional study. We studied 74 adult hypopituitary patients (males, 43; females, 31; mean age, 57 years; and range, 23-79) with central hypothyroidism treated with l-T4 (median daily dose: 1.1  μg/kg). All patients also had severe GH deficiency (GHD) and 38 of them were replaced with recombinant GH. Vertebral fractures were assessed by a quantitative morphometric analysis performed on thoracic and lumbar spine lateral X-ray. Radiological vertebral fractures were found in 23 patients (31.1%) in association with untreated GHD (P=0.02), higher serum free T4 levels (P=0.03), a higher daily dose of l-T4 (P=0.005), and a longer duration of hypopituitarism (P=0.05). When GHD was treated, the prevalence of vertebral fractures was more frequent (P=0.03) in patients receiving high l-T4 doses (third tertile: >1.35  μg/kg per day) as compared with patients who were treated with lower drug doses (first tertile: hypopituitarism. © 2014 European Society of Endocrinology.

Sex steroids and the GH axis: Implications for the management of hypopituitarism.

Science.gov (United States)

Birzniece, Vita; Ho, Ken K Y

2017-02-01

Growth hormone (GH) regulates somatic growth, substrate metabolism and body composition. Sex hormones exert profound effect on the secretion and action of GH. Estrogens stimulate the secretion of GH, but inhibit the action of GH on the liver, an effect that occurs when administered orally. Estrogens suppress GH receptor signaling by stimulating the expression proteins that inhibit cytokine receptor signaling. This effect of estrogens is avoided when physiological doses of estrogens are administered via a non-oral route. Estrogen-like compounds, such as selective estrogen receptor modulators, possess dual properties of inhibiting the secretion as well as the action of GH. In contrast, androgens stimulate GH secretion, driving IGF-1 production. In the periphery, androgens enhance the action of GH. The differential effects of estrogens and androgens influence the dose of GH replacement in patients with hypopituitarism on concomitant treatment with sex steroids. Where possible, a non-oral route of estrogen replacement is recommended for optimizing cost-benefit of GH replacement in women with GH deficiency. Adequate androgen replacement in conjunction with GH replacement is required to achieve the full anabolic effect in men with hypopituitarism. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gender and age influence the relationship between serum GH and IGF-I in patients with acromegaly.

Science.gov (United States)

Parkinson, C; Renehan, A G; Ryder, W D J; O'Dwyer, S T; Shalet, S M; Trainer, P J

2002-07-01

In patients with acromegaly serum IGF-I is increasingly used as a marker of disease activity. As a result, the relationship between serum GH and IGF-I is of profound interest. Healthy females secrete three times more GH than males but have broadly similar serum IGF-I levels, and women with GH deficiency require 30-50% more exogenous GH to maintain the same serum IGF-I as GH-deficient men. In a selected cohort of patients with active acromegaly, studied off medical therapy using a single fasting serum GH and IGF-I measurement, we have reported previously that, for a given GH level, women have significantly lower circulating IGF-I. To evaluate the influence of age and gender on the relationship between serum GH and IGF-I in an unselected cohort of patients with acromegaly independent of disease control and medical therapy. Sixty (34 male) unselected patients with acromegaly (median age 51 years (range 24-81 years) attending a colonoscopy screening programme were studied. Forty-five had previously received pituitary radiotherapy. Patients had varying degrees of disease control and received medical therapy where appropriate. Mean serum GH was calculated from an eight-point day profile (n = 45) and values obtained during a 75-g oral glucose tolerance test (n = 15). Serum IGF-I, IGFBP-3 and acid-labile subunit were measured and the dependency of these factors on covariates such as log10 mean serum GH, sex, age and prior radiotherapy was assessed using regression techniques. The median calculated GH value was 4.7 mU/l (range 1-104). A significant linear association was observed between serum IGF-I and log10 mean serum GH for the cohort (R = 0.5, P fall by 0.37 nmol/l per year (P = 0.04, 95% CI 0.015-0.72). In keeping with previous observations of relative GH resistance in normal and GH-deficient females we have observed lower serum IGF-I levels for equivalent mean serum GH levels in females patients with acromegaly. This gender-dependent difference is independent of

The evolution of radiation-induced growth hormone deficiency in adults is determined by the baseline growth hormone status

Energy Technology Data Exchange (ETDEWEB)

Toogood, A.A.; Ryder, W.D.J.; Beardwell, C.G.; Shalet, S.M. [Christie Hospital and Holt Radium Inst., Manchester (United Kingdom)

1995-07-01

Recent studies of GH replacement have suggested several beneficial effects for GH deficient adults. It would therefore be helpful to predict the time of onset of GH deficiency after external pituitary irradiation. We have studied the evolution of GH deficiency with time in patients irradiated for pituitary adenomas and other hypothalamic pituitary tumours. The results provide an insight into the pattern of the decline in GH secretion following radiotherapy in patients with pituitary disease and the factors affecting it. This information will help the clinician predict the frequency and timing of GH deficiency in patients irradiated for pituitary disease and the potential need for GH replacement therapy. (Author).

The rationale and design of TransCon Growth Hormone for the treatment of growth hormone deficiency

Directory of Open Access Journals (Sweden)

Kennett Sprogøe

2017-10-01

Full Text Available The fundamental challenge of developing a long-acting growth hormone (LAGH is to create a more convenient growth hormone (GH dosing profile while retaining the excellent safety, efficacy and tolerability of daily GH. With GH receptors on virtually all cells, replacement therapy should achieve the same tissue distribution and effects of daily (and endogenous GH while maintaining levels of GH and resulting IGF-1 within the physiologic range. To date, only two LAGHs have gained the approval of either the Food and Drug Administration (FDA or the European Medicines Agency (EMA; both released unmodified GH, thus presumably replicating distribution and pharmacological actions of daily GH. Other technologies have been applied to create LAGHs, including modifying GH (for example, protein enlargement or albumin binding such that the resulting analogues possess a longer half-life. Based on these approaches, nearly 20 LAGHs have reached various stages of clinical development. Although most have failed, lessons learned have guided the development of a novel LAGH. TransCon GH is a LAGH prodrug in which GH is transiently bound to an inert methoxy polyethylene glycol (mPEG carrier. It was designed to achieve the same safety, efficacy and tolerability as daily GH but with more convenient weekly dosing. In phase 2 trials of children and adults with growth hormone deficiency (GHD, similar safety, efficacy and tolerability to daily GH was shown as well as GH and IGF-1 levels within the physiologic range. These promising results support further development of TransCon GH.

Administration route-dependent effects of estrogens on IGF-I levels during fixed GH replacement in women with hypopituitarism

NARCIS (Netherlands)

van der Klaauw, Agatha A.; Biermasz, Nienke R.; Zelissen, Pierre M. J.; Pereira, Alberto M.; Lentjes, Eef G. W. M.; Smit, Johannes W. A.; van Thiel, Sjoerd W.; Romijn, Johannes A.; Roelfsema, Ferdinand

2007-01-01

GH-deficient women using oral estradiol treatment require higher doses of recombinant human GH (rhGH) to achieve similar IGF-I levels when compared with men and women on transdermal estradiol replacement. The aim of this study was to evaluate the effects of oral versus transdermal estrogen

Do deficiencies in growth hormone and insulin-like growth factor-1 (IGF-1) shorten or prolong longevity?

Science.gov (United States)

Laron, Zvi

2005-02-01

Present knowledge on the effects of growth hormone (GH) and insulin-like growth factor-I (IGF-I) deficiency on aging and lifespan are controversial. Studying untreated patients with either isolated GH deficiency due to GH gene deletion, patients with multiple pituitary hormone deficiency due to PROP-1 gene mutation and patients with isolated IGF-I deficiency due to deletions or mutations of the GH receptor gene (Laron syndrome); it was found, that these patients despite signs of early aging (wrinkled skin, obesity, insulin resistance and osteopenia) have a long life span reaching ages of 80-90 years. Animal models of genetic GH deficiencies such as Snell mice (Pit-1 gene mutations) the Ames mice (PROP-1 gene mutation) and the Laron mice (GH receptor gene knock-out) have a statistically significant higher longevity compared to normal controls. On the contrary, mice transgenic for GH and acromegalic patients secreting high amounts of GH have premature death. Those data raise the question whether pharmacological GH administration to adults is deleterious, in contrast to policies advocating such therapies.

Differential effects of hGH and IGF-I on body proportions.

Science.gov (United States)

Laron, Zvi; Silbergeld, Aviva; Kauli, Rivka

2012-07-01

The differential growth effects of hGH and IGF-I on the upper/lower (U/L) body segment in relation to height (Ht) were analyzed in 15 patients with isolated Growth hormone deficiency (IGHD,:7M, 8F) mean age 5.0 +/- 3.2 (SD) years treated with hGH; 21 patients with multiple pituitary hormone deficiency including growth hormone (MPHD: 14M, 7F) aged 10.0 +/- 3.8, treated with hGH; 9 patients with Laron Syndrome (LS) (4M,5F) aged 6.9 +/- 5.6 years treated with IGF-I; 9 boys with intrauterine growth retardation (IUGR) aged 6.3 +/- 1.25 years treated by hGH; and 22 boys with idiopathic short stature (ISS) aged 8.0 +/- 1.55 years treated by hGH. The dose of hGH was 33 microg/kg/day, that of IGF-I 180-200 microg/kg/day. the U/L body segment ratio in IGHD patients decreased from 2.3 +/- 0.7 to 1.1 +/- 0.7 (p <0.001), and the Ht SDS increased from -4.9 +/- 1.3 to 2.3 +/- 1 (p < 0.001) following treatment. In MPHD patients the U/L body segment decreased from 1.1 +/- 1.1 to -0.6 +/- 1.0 (p < 0.001), and the Ht SDS increased from -3.3 +/- 1.4 to -2.5 +/- 1.0 (p < 0.009). In the LS group the U/L body segment ratio did not change with IGF-I treatment but Ht improved from -6.1 +/- 1.3 to -4.6 +/- 1.2 (p < 0.001), The differential growth response of the children with IUGR and with ISS resembled that of the children with LS. hGH and IGF-I act differentially on the spine and limbs.

Response of Indian growth hormone deficient children to growth hormone therapy: association with pituitary size.

Science.gov (United States)

Khadilkar, Vaman V; Prasad, Hemchand Krishna; Ekbote, Veena H; Rustagi, Vaishakhi T; Singh, Joshita; Chiplonkar, Shashi A; Khadilkar, Anuradha V

2015-05-01

To ascertain the impact of pituitary size as judged by Magnetic Resonance Imaging (MRI), on response to Growth Hormone (GH) therapy in GH deficient children. Thirty nine children (9.1 ± 2.7 y, 22 boys) with non-acquired GH deficiency (21 Isolated GH deficiency and 18 Combined pituitary hormone deficiency) were consecutively recruited and followed up for one year. Clinical, radiological (bone age and MRI) and biochemical parameters were studied. Children with hypoplastic pituitary (pituitary height deficit (height for age Z-score -6.0 vs. -5.0) and retardation of skeletal maturation (bone age chronological age ratio of 0.59 vs. 0.48) at baseline as compared to children with normal pituitary heights (p growth hormone deficient children with hypoplastic pituitary respond better to therapy with GH in short term.

Bioavailability and bioactivity of intravenous vs subcutaneous infusion of growth hormone in GH-deficient patients

DEFF Research Database (Denmark)

Laursen, Torben; Møller, Jens; Ørskov, Hans

1996-01-01

Abstract OBJECTIVE: The bioavailability of GH immunoreactive serum concentrations is reduced following subcutaneous (s.c.) as compared with intravenous (i.v.) administration. Whether this difference also translates into a different biological activity remains to be investigated. The aim of the pr......Abstract OBJECTIVE: The bioavailability of GH immunoreactive serum concentrations is reduced following subcutaneous (s.c.) as compared with intravenous (i.v.) administration. Whether this difference also translates into a different biological activity remains to be investigated. The aim...... = 0.09) were observed on the two occasions. CONCLUSIONS: A reduced bioavailability of s.c. as compared with i.v. administered GH has been recorded with two independent GH assays, and this was also accompanied by a significant, albeit modest, reduction in biological activity....

Liver-derived IGF-I contributes to GH-dependent increases in lean mass and bone mineral density in mice with comparable levels of circulating GH.

Science.gov (United States)

Nordstrom, Sarah M; Tran, Jennifer L; Sos, Brandon C; Wagner, Kay-Uwe; Weiss, Ethan J

2011-07-01

The relative contributions of circulating and locally produced IGF-I in growth remain controversial. The majority of circulating IGF-I is produced by the liver, and numerous mouse models have been developed to study the endocrine actions of IGF-I. A common drawback to these models is that the elimination of circulating IGF-I disrupts a negative feedback pathway, resulting in unregulated GH secretion. We generated a mouse with near total abrogation of circulating IGF-I by disrupting the GH signaling mediator, Janus kinase (JAK)2, in hepatocytes. We then crossed these mice, termed JAK2L, to GH-deficient little mice (Lit). Compound mutant (Lit-JAK2L) and control (Lit-Con) mice were treated with equal amounts of GH such that the only difference between the two groups was hepatic GH signaling. Both groups gained weight in response to GH but there was a reduction in the final weight of GH-treated Lit-JAK2L vs. Lit-Con mice. Similarly, lean mass increased in both groups, but there was a reduction in the final lean mass of Lit-JAK2L vs. Lit-Con mice. There was an equivalent increase in skeletal length in response to GH in Lit-Con and Lit-JAK2L mice. There was an increase in bone mineral density (BMD) in both groups, but Lit-JAK2L had lower BMD than Lit-Con mice. In addition, GH-mediated increases in spleen and kidney mass were absent in Lit-JAK2L mice. Taken together, hepatic GH-dependent production of IGF-I had a significant and nonredundant role in GH-mediated acquisition of lean mass, BMD, spleen mass, and kidney mass; however, skeletal length was dependent upon or compensated for by locally produced IGF-I.

Nonalcoholic fatty liver in patients with Laron syndrome and GH gene deletion - preliminary report.

Science.gov (United States)

Laron, Zvi; Ginsberg, Shira; Webb, Muriel

2008-10-01

There is little information on the relationship between growth hormone/insulin-like growth factor-I (GH/IGF-I) deficiency or IGF-I treatment on nonalcoholic fatty liver disease (NAFLD) a disorder linked to obesity and insulin resistance. To find out whether the markedly obese patients with Laron syndrome (LS) and GH gene deletion have fatty livers. We studied 11 untreated adult patients with LS (5M, 6F), five girls with LS treated by IGF-I and five adult patients with GH gene deletion (3M, 3F), four previously treated by hGH in childhood. Fatty liver was quantitatively evaluated by ultrasonography using a phase array US system (HITACHI 6500, Japan). Body adiposity was determined by DEXA, and insulin resistance was estimated by HOMA-IR using the fasting serum glucose and insulin values. Six out of 11 adult patients with LS, two out of the five IGF-I treated girls with LS and three out of five adult hGH gene deletion patients were found to have NAFLD (nonalcoholic fatty liver disease). NAFLD is a frequent complication in untreated and treated congenital IGF-I deficiency. No correlation between NAFLD and age, sex, degree of obesity, blood lipids, or degree of insulin resistance was observed.

Is increase in bone mineral content caused by increase in skeletal muscle mass/strength in adult patients with GH-treated GH deficiency?

DEFF Research Database (Denmark)

Klefter, Oliver; Feldt-Rasmussen, Ulla

2009-01-01

to a muscle modulating effect, and if treatment with GH would primarily increase muscle mass and strength with a secondary increase in BMD/BMC, thus supporting the present physiological concept that mass and strength of bones are mainly determined by dynamic loads from the skeletal muscles. METHOD: We...... performed a systematic literature analysis, including 51 clinical trials published between 1996 and 2008, which had studied the development in muscle mass, muscle strength, BMD, and/or BMC in GH-treated adult GHD patients. RESULTS: GH therapy had an anabolic effect on skeletal muscle. The largest increase...... in muscle mass occurred during the first 12 months of therapy. Most trials measuring BMD/BMC reported significant increases from baseline values. The significant increases in BMD/BMC occurred after 12-18 months of treatment, i.e. usually later than the increases in muscle parameters. Only seven trials...

Different growth hormone (GH) response to GH-releasing peptide and GH-releasing hormone in hyperthyroidism.

Science.gov (United States)

Ramos-Dias, J C; Pimentel-Filho, F; Reis, A F; Lengyel, A M

1996-04-01

Altered GH responses to several pharmacological stimuli, including GHRH, have been found in hyperthyroidism. The mechanisms underlying these disturbances have not been fully elucidated. GH-releasing peptide-6 (GHRP-6) is a synthetic hexapeptide that specifically stimulates GH release both in vitro and in vivo. The mechanism of action of GHRP-6 is unknown, but it probably acts by inhibiting the effects of somatostatin on GH release. The aim of this study was to evaluate the effects of GHRP-6 on GH secretion in patients with hyperthyroidism (n = 9) and in control subjects (n = 9). Each subject received GHRP-6 (1 microg/kg, iv), GHRH (100 microg, iv), and GHRP-6 plus GHRH on 3 separate days. GH peak values (mean +/- SE; micrograms per L) were significantly lower in hyperthyroid patients compared to those in control subjects after GHRH alone (9.0 +/- 1.3 vs. 27.0 +/- 5.2) and GHRP-6 plus GHRH (22.5 +/- 3.5 vs. 83.7 +/- 15.2); a lack of the normal synergistic effect of the association of both peptides was observed in thyrotoxicosis. However, a similar GH response was seen in both groups after isolated GHRP-6 injection (31.9 +/- 5.7 vs. 23.2 +/- 3.9). In summary, we have shown that hyperthyroid patients have a normal GH response to GHRP-6 together with a blunted GH responsiveness to GHRH. Our data suggest that thyroid hormones modulate GH release induced by these two peptides in a differential way.

Transient urinary retention and chronic neuropathic pain associated with genital herpes simplex virus infection.

Science.gov (United States)

Haanpää, Maija; Paavonen, Jorma

2004-10-01

Genital herpes (GH) causes genital ulcer disease, severe transient pain, and often paresthesias. Whether or not GH can cause urinary retention or chronic neuropathic pain is not well known. We present two immunocompetent patients with GH associated with neuropathic symptoms. We also review the literature on GH and associated neurologic problems. Patient 1 had primary herpes simplex virus (HSV)-2 infection with transient urinary retention and chronic bilateral neuropathic pain in the sacral area. Patient 2 had recurrent HSV-1 associated with unitaleral chronic neuropathic pain in the sacral area. Although transient urinary retention associated with GH is not uncommon, chronic neuropathic pain has not been reported previously. Our cases show that chronic neuropathic pain, that is "pain initiated or caused by a primary lesion or dysfunction in the nervous system," can follow genital HSV infection.

Growth hormone deficiency and hyperthermia during exercise

DEFF Research Database (Denmark)

Juul, A; Hjortskov, N; Jepsen, Leif

1995-01-01

-deficiency may be at risk for developing hyperthermia. To pursue this, we performed a controlled study on sweating and body temperature regulation during exercise in the heat in 16 GH-treated GH-deficient patients with normalized insulin-like growth factor-I and insulin-like growth factor/binding protein-3 serum.......001]. Consequently, the core temperatures of the patients increased significantly after exercise compared with those of the CTs [38.3 C (0.10 C) (MPD) and 38.1 C (0.06 C) (isolated GH deficiency) vs. 37.5 C (0.2 C) (CTs) (P temperature increased significantly during exercise in the patients...... but remained unaltered in the CTs. Sweat secretion rates, as determined by the pilocarpine method, were significantly lower in the MPD patients [77 (SE +/- 10) mg/30 min] than in the CTs [115 (SE +/- 7) mg/30 min] (P

Improved growth response to GH treatment in irradiated children

International Nuclear Information System (INIS)

Lannering, B.; Albertsson-Wikland, K.

1989-01-01

The growth response to two years of GH treatment was studied in fifteen children after radiotherapy for a cranial tumour. The growth response was compared to that of short children (-2 SD) and that of children with idiopathic growth hormone deficiency (GHD) of similar ages. All children were treated with hGH 0.1 IU/kg/day s.c.; which is a higher dose and frequency than previously reported for irradiated children. On this protocol the growth rate increased 5.0 +- 0.5 cm/y (mean +- SEM) the first year and 3.8 +- 0.7 cm/y the second year compared to the growth rate the year before GH-treatment. Although the net gain in growth was higher than previously reported, the first year growth response was significantly reduced (p less than 0.05) compared to that of GHD-children (7.6 +- 0.5 cm/y) but exceeded (p less than 0.05) that of short children (3.4 +- 0.3 cm/y). The median spontaneous 24 h-GH secretion was 209 mU/l in the short children, 52 mU/l in the irradiated children and 16 mU/l in the idiopathic GHD children. Thus the growth increment varied inversely to the spontaneous GH secretion observed in the three groups

Distinct cytoplasmic domains of the growth hormone receptor are required for glucocorticoid- and phorbol ester-induced decreases in growth hormone (GH) binding. These domains are different from that reported for GH-induced receptor internalization

DEFF Research Database (Denmark)

King, A P; Tseng, M J; Logsdon, C D

1996-01-01

Glucocorticoids inhibit growth in children and antagonize the growth-promoting action of GH in peripheral tissues. Recently, they have been shown to decrease GH binding. In this study we examine the molecular mechanisms by which the glucocorticoid dexamethasone (DEX) and the phorbol ester phorbol...... of GH binding are also observed in a Chinese hamster ovary (CHO) cell line stably transfected with a rat liver GHR cDNA, further arguing that DEX and PMA act post-translationally on GHR. Using mutant GHRs stably expressed in CHO cells, amino acids 455-506 and tyrosines 333 and/or 338 of GHR were shown...... to be required for maximal DEX-induced inhibition of GH binding. DEX decreased GH binding to a GHR mutant F346A, which is reported to be deficient in ligand-induced internalization, suggesting that DEX decreases GH binding by a mechanism distinct from that of ligand-induced GHR internalization. PMA reduced GH...

Spontaneous growth in growth hormone deficiency from birth until 7 years of age: development of disease-specific growth curves.

Science.gov (United States)

Mayer, M; Schmitt, K; Kapelari, K; Frisch, H; Köstl, G; Voigt, M

2010-01-01

Little is known about spontaneous growth of growth hormone (GH)-deficient children during infancy and childhood. Retrospectively, we calculated disease-specific pretreatment percentiles for height, weight, BMI and growth velocity of 113 GH-deficient boys and 41 GH-deficient girls from birth until 7 years of age, by mean and standard deviation. Infants with idiopathic GH deficiency (GHD) grow in disease-specific percentile channels. There is a significant difference in length and weight from birth onward compared to regional reference (pgrowth velocity, despite a wide variance in the first years, so height deficit became more evident with increasing age. GHD is a congenital disease no matter when height deficit becomes clinically evident, because GH-deficient children grow in disease-specific percentile channels with a highly significantly reduced length and weight, which demonstrates that GH is essential for adequate growth in infancy and early childhood. Copyright (c) 2010 S. Karger AG, Basel.

A mathematical model for interpreting in vitro rhGH release from laminar implants.

Science.gov (United States)

Santoveña, A; García, J T; Oliva, A; Llabrés, M; Fariña, J B

2006-02-17

Recombinant human growth hormone (rhGH), used mainly for the treatment of growth hormone deficiency in children, requires daily subcutaneous injections. The use of controlled release formulations with appropriate rhGH release kinetics reduces the frequency of medication, improving patient compliance and quality of life. Biodegradable implants are a valid alternative, offering the feasibility of a regular release rate after administering a single dose, though it exists the slight disadvantage of a very minor surgical operation. Three laminar implant formulations (F(1), F(2) and F(3)) were produced by different manufacture procedures using solvent-casting techniques with the same copoly(D,L-lactic) glycolic acid (PLGA) polymer (Mw=48 kDa). A correlation in vitro between polymer matrix degradation and drug release rate from these formulations was found and a mathematical model was developed to interpret this. This model was applied to each formulation. The obtained results where explained in terms of manufacture parameters with the aim of elucidate whether drug release only occurs by diffusion or erosion, or by a combination of both mechanisms. Controlling the manufacture method and the resultant changes in polymer structure facilitates a suitable rhGH release profile for different rhGH deficiency treatments.

A case of myxedema coma caused by isolated thyrotropin stimulating hormone deficiency and Hashimoto's thyroiditis.

Science.gov (United States)

Iida, Keiji; Hino, Yasuhisa; Ohara, Takeshi; Chihara, Kazuo

2011-01-01

Myxedema coma (MC) is a rare, but often fatal endocrine emergency. The majority of cases that occur in elderly women with long-standing primary hypothyroidism are caused by particular triggers. Conversely, MC of central origin is extremely rare. Here, we report a case of MC with both central and primary origins. A 56-year-old woman was transferred to our hospital due to loss of consciousness; a chest x-ray demonstrated severe cardiomegaly. Low body temperature, bradycardia, and pericardial effusion suggested the presence of hypothyroidism. Endocrinological examination revealed undetectable levels of serum free thyroxine (T(4)) and free triiodothyronine (T(3)), whereas serum thyroid-stimulating hormone (TSH) levels were not elevated. The woman's serum anti-thyroid peroxidase antibody and anti-thyroglobulin antibody tests were positive, indicating that she had Hashimoto's thyroiditis. Provocative tests to the anterior pituitary revealed that she had TSH and growth hormone (GH) deficiency; however, GH levels were restored after supplementation with levothyroxine for 5 months. This was not only a rare case of MC with TSH deficiency and Hashimoto's thyroiditis; the patient also developed severe osteoporosis and possessed transient elevated levels of serum carcinoembryonic antigen (CEA). This atypical case may suggest the role of anterior pituitary hormone deficiencies, as well as hypothyroidism, in the regulation of bone metabolism.

Bartter syndrome and growth hormone deficiency: three cases.

Science.gov (United States)

Buyukcelik, Mithat; Keskin, Mehmet; Kilic, Beltinge Demircioglu; Kor, Yilmaz; Balat, Ayse

2012-11-01

Bartter syndrome is a rare autosomal recessive disorder characterized by hypokalemia, salt loss, and metabolic alkalosis. Short stature is one of the clinical manifestations in these children. Although polyuria, polydipsia, hypokalemia, and salt loss may be responsible for growth retardation, the exact pathogenesis of short stature in Bartter syndrome is not known. In this study, we present three children diagnosed as having Bartter syndrome with short stature and growth hormone (GH) deficiency. After recombinant human growth hormone therapy (rhGH), their growth velocities were improved. These results indicate that GH deficiency may contribute to short stature in children with Bartter syndrome, and rhGH therapy would be an excellent adjunctive treatment for short children with this syndrome whose condition is resistant to conventional therapies in terms of growth.

Autosomal Dominant Growth Hormone Deficiency (Type II).

Science.gov (United States)

Alatzoglou, Kyriaki S; Kular, Dalvir; Dattani, Mehul T

2015-06-01

Isolated growth hormone deficiency (IGHD) is the commonest pituitary hormone deficiency resulting from congenital or acquired causes, although for most patients its etiology remains unknown. Among the known factors, heterozygous mutations in the growth hormone gene (GH1) lead to the autosomal dominant form of GHD, also known as type II GHD. In many cohorts this is the commonest form of congenital isolated GHD and is mainly caused by mutations that affect the correct splicing of GH-1. These mutations cause skipping of the third exon and lead to the production of a 17.5-kDa GH isoform that exerts a dominant negative effect on the secretion of the wild type GH. The identification of these mutations has clinical implications for the management of patients, as there is a well-documented correlation between the severity of the phenotype and the increased expression of the 17.5-kDa isoform. Patients with type II GHD have a variable height deficit and severity of GHD and may develop additional pituitary hormone defiencies over time, including ACTH, TSH and gonadotropin deficiencies. Therefore, their lifelong follow-up is recommended. Detailed studies on the effect of heterozygous GH1 mutations on the trafficking, secretion and action of growth hormone can elucidate their mechanism on a cellular level and may influence future treatment options for GHD type II.

Human GH Receptor-IGF-1 Receptor Interaction: Implications for GH Signaling

Science.gov (United States)

Gan, Yujun; Buckels, Ashiya; Liu, Ying; Zhang, Yue; Paterson, Andrew J.; Jiang, Jing; Zinn, Kurt R.

2014-01-01

GH signaling yields multiple anabolic and metabolic effects. GH binds the transmembrane GH receptor (GHR) to activate the intracellular GHR-associated tyrosine kinase, Janus kinase 2 (JAK2), and downstream signals, including signal transducer and activator of transcription 5 (STAT5) activation and IGF-1 gene expression. Some GH effects are partly mediated by GH-induced IGF-1 via IGF-1 receptor (IGF-1R), a tyrosine kinase receptor. We previously demonstrated in non-human cells that GH causes formation of a GHR-JAK2-IGF-1R complex and that presence of IGF-1R (even without IGF-1 binding) augments proximal GH signaling. In this study, we use human LNCaP prostate cancer cells as a model system to further study the IGF-1R's role in GH signaling. GH promoted JAK2 and GHR tyrosine phosphorylation and STAT5 activation in LNCaP cells. By coimmunoprecipitation and a new split luciferase complementation assay, we find that GH augments GHR/IGF-1R complex formation, which is inhibited by a Fab of an antagonistic anti-GHR monoclonal antibody. Short hairpin RNA-mediated IGF-1R silencing in LNCaP cells reduced GH-induced GHR, JAK2, and STAT5 phosphorylation. Similarly, a soluble IGF-1R extracellular domain fragment (sol IGF-1R) interacts with GHR in response to GH and blunts GH signaling. Sol IGF-1R also markedly inhibits GH-induced IGF-1 gene expression in both LNCaP cells and mouse primary osteoblast cells. On the basis of these and other findings, we propose a model in which IGF-1R augments GH signaling by allowing a putative IGF-1R-associated molecule that regulates GH signaling to access the activated GHR/JAK2 complex and envision sol IGF-1R as a dominant-negative inhibitor of this IGF-1R-mediated augmentation. Physiological implications of this new model are discussed. PMID:25211187

HDL cholesterol response to GH replacement is associated with common cholesteryl ester transfer protein gene variation (-629C>A) and modified by glucocorticoid treatment

NARCIS (Netherlands)

Dullaart, Robin P. F.; van den Berg, Gerrit; van der Knaap, Aafke M.; Dijck-Brouwer, Janneke; Dallinga-Thie, Geesje M.; Zelissen, Peter M. J.; Sluiter, Wim J.; van Beek, André P.

2010-01-01

GH replacement lowers total cholesterol and low-density lipoprotein cholesterol (LDL-C) in GH-deficient adults, but effects on high-density lipoprotein (HDL) cholesterol (HDL-C) are variable. Both GH and glucocorticoids decrease cholesteryl ester transfer protein (CETP) activity, which is important

Growth hormone (GH) binding and effects of GH analogs in transgenic mice

Energy Technology Data Exchange (ETDEWEB)

Bartke, A.; Steger, R.W. [Southern Illinois Univ., Carbondale, IL (United States); Turyn, D. [UBA-CONICET, Buenos Aires (Argentina)] [and others

1994-12-31

Overexpression of human (h) or bovine (b) growth hormone (GH) in transgenic mice is associated with marked (2- to 12-fold) and significant increase in hepatic binding of GH and prolactin (PRL). This is due to an increase in the number of GH and PRL receptors (GHR, PRLR) per mg of microsomal protein without changes in binding affinity. Comparison of results obtained in transgenic animals expressing bGH with a mouse metallothionein (MT) or a rat phosphoenolpyruvate carboxykinase (PEPCK) promoter suggests that effects of bGH on hepatic GHR and PRLR do not require GH overexpression during fetal life and, within the dose range tested, the effects on PRLR are not dose dependent. The increase in hepatic GHR was accompanied by significant increases in plasma GH-binding protein (GHBP) and in mean residence time of injected GH. Thus life-long elevation of peripheral GH levels alters the availability of both free GH and GHR. Site-directed in vitro mutagenesis was used to produce hGH and bGH analogs mutated within one of the sites involved in binding to GHR and PRLR. Mutating hGH to produce amino acid identity with bGH at Position 11, 18 (within Helix 1), 57, or 60 (within the loop between Helix 1 and 2) did not affect binding to GHR in vitro, or somatotropic activity in transgenic mice in vivo but reduced lactogenic activity in Nb{sub 2} cells by 22%-45%. Mutations of bGH designed to produce amino acid identity with hGH at one to four of the corresponding positions in the bGH molecule did not interfere with binding to GHR or somatotropic activity in vivo, and failed to produce significant binding to PRLR but resulted in alterations in the effects on the hypothalamic and anterior pituitary function in transgenic mice. Apparently region(s) outside the domains examined are essential for lactogenic activity of hGH, and different portions of the GH molecule are responsible for its diverse actions in vivo. 35 refs.

Effect of long-term growth hormone treatment on bone mass and bone metabolism in growth hormone-deficient men

NARCIS (Netherlands)

Bravenboer, N; Holzmann, PJ; ter Maaten, JC; Stuurman, LM; Roos, JC; Lips, P

2005-01-01

Long-term GH treatment in GH-deficient men resulted in a continuous increase in bone turnover as shown by histomorphometry. BMD continuously increased in all regions of interest, but more in the regions with predominantly cortical bone. Introduction: Adults with growth hormone (GH) deficiency have

Growth Hormone Deficiency in a Patient with Becker Muscular Dystrophy: A Pediatric Case Report

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Valeria Calcaterra

2013-01-01

Full Text Available Objective. To describe a biochemical growth hormone (GH deficiency and to evaluate therapeutic result in a six-year-old male with Becker muscular dystrophy (BMD. Methods. GH peak was evaluated after response to arginine and insulin. Bone age was evaluated according to Greulich and Pyle method. Results. The GH-supplementary therapy was very effective in terms of growth gain. Conclusion. The possibility of a growth hormone deficiency and treatment with GH in patients with BMD cannot be excluded, especially considering the good therapeutic response.

Growth hormone effects on cortical bone dimensions in young adults with childhood-onset growth hormone deficiency

DEFF Research Database (Denmark)

Hyldstrup, L; Conway, G S; Racz, K

2012-01-01

Growth hormone (GH) treatment in young adults with childhood-onset GH deficiency has beneficial effects on bone mass. The present study shows that cortical bone dimensions also benefit from GH treatment, with endosteal expansion and increased cortical thickness leading to improved bone strength....... INTRODUCTION: In young adults with childhood-onset growth hormone deficiency (CO GHD), GH treatment after final height is reached has been shown to have beneficial effects on spine and hip bone mineral density. The objective of the study was to evaluate the influence of GH on cortical bone dimensions. METHODS...

Effect of growth hormone-releasing factor on growth hormone release in children with radiation-induced growth hormone deficiency

International Nuclear Information System (INIS)

Lustig, R.H.; Schriock, E.A.; Kaplan, S.L.; Grumbach, M.M.

1985-01-01

Five male children who received cranial irradiation for extrahypothalamic intracranial neoplasms or leukemia and subsequently developed severe growth hormone (GH) deficiency were challenged with synthetic growth hormone-releasing factor (GRF-44), in an attempt to distinguish hypothalamic from pituitary dysfunction as a cause of their GH deficiency, and to assess the readily releasable GH reserve in the pituitary. In response to a pulse of GRF-44 (5 micrograms/kg intravenously), mean peak GH levels rose to values higher than those evoked by the pharmacologic agents L-dopa or arginine (6.4 +/- 1.3 ng/mL v 1.5 +/- 0.4 ng/mL, P less than .05). The peak GH value occurred at a mean of 26.0 minutes after administration of GRF-44. These responses were similar to those obtained in children with severe GH deficiency due to other etiologies (peak GH 6.3 +/- 1.7 ng/mL, mean 28.0 minutes). In addition, there was a trend toward an inverse relationship between peak GH response to GRF-44 and the postirradiation interval. Prolactin and somatomedin-C levels did not change significantly after the administration of a single dose of GRF-44. The results of this study support the hypothesis that cranial irradiation in children can lead to hypothalamic GRF deficiency secondary to radiation injury of hypothalamic GRF-secreting neurons. This study also lends support to the potential therapeutic usefulness of GRF-44 or an analog for GH deficiency secondary to cranial irradiation

Similar effects of long-term exogenous growth hormone (GH) on bone and muscle parameters: a pQCT study of GH-deficient and small-for-gestational-age (SGA) children.

Science.gov (United States)

Schweizer, Roland; Martin, David D; Haase, Martin; Roth, Johannes; Trebar, Branko; Binder, Gerhard; Schwarze, C Philipp; Ranke, Michael B

2007-11-01

Treatment with GH in short children has focused on height development. Little is known about the concomitant changes in muscle mass, bone structure and bone strength. Muscle area as well as parameters of bone architecture (bone mineral content, BMC; volumetric cortical density, total bone area, TBA; cortical area, cortical thickness, CT; and marrow area) were measured by means of pQCT (Stratec) at 65% of the proximal length of the forearm. The strength-strain index (SSI) was calculated as an indicator of bone strength. Prepubertal children with GHD (mean values: age; 7.2 years; height SDS=-2.9 SDS; GH dose: 30 microg/kg/d) were followed at 0, 6, 12 (n=74) and 24 (n=55) months. Prepubertal children with SGA (mean values: age: 7.1 years; height SDS=-3.4 SDS; GH dose: 55 mug/kg/d) were followed at 0, 6, 12 (n=47) and 24 (n=35) months. Both groups showed a similar increase in height. At GH start, muscle mass and bone characteristics were lower than normal but similar in SGA vs. GHD. Muscle area (mean values, SDS) increased from -3.0 to -1.5 in SGA and from -2.4 to -1.0 in GHD. Bone geometry changed in a biphasic mode, with an increase in total bone area and lowering of bone mineral content (BMC) during the first 12 months, followed by an increase of BMC and CT thereafter. SSI (mean values, mm(3)) improved from 78 to 114 in GHD and from 62 to 101 in SGA after 24 months on GH. The increment in terms of SDS did not reach significance in SGA. SSI correlated positively with muscle area before and during GH treatment. Bone strength and muscle mass are impaired in prepubertal children with GHD and SGA. Exogenous GH can indirectly improve bone structure and strength by inducing an increase in muscle mass. Our findings support the assumption that, in SGA, there is impaired tissue responsiveness to GH.

Growth hormone treatment during pregnancy in a growth hormone-deficient woman

DEFF Research Database (Denmark)

Müller, J; Starup, J; Christiansen, J S

1995-01-01

Information on the course and outcome of pregnancies in growth hormone (GH)-deficient patients is sparse, and GH treatment during pregnancy in such women has not been described previously. We have studied fetal growth and serum levels of GH, insulin-like growth factor I (IGF-I) and IGF binding...

Iron-Deficiency Anemia Leading to Transient Ischemic Attacks due to Intraluminal Carotid Artery Thrombus

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H. Z. Batur Caglayan

2013-01-01

Full Text Available Reactive thrombocytosis secondary to iron-deficiency anemia (IDA is a rare but recognized cause of stroke. We report the case of a patient with iron-deficiency anemia presenting with multiple transient ischemic attacks (TIA due to intraluminal thrombus of an internal carotid artery. The putative mechanisms underlying anemia and stroke syndromes are not completely understood, and it is believed that iron deficiency may cause ischemic stroke by several potential mechanisms. Thrombocytosis is often associated with iron deficiency, and microcytosis produces a reduction in the red cell deformability and could produce a hypercoagulable state. The platelet count and function observed in iron-deficiency anemia could act synergistically to promote thrombus formation, especially in the setting of an underlying atherosclerotic disease. The presence of floating thrombus in a patient with clinical and MRI evidence of stroke represents a significant therapeutic dilemma and requires immediate decision about treatment.

Growth hormone treatment in non-growth hormone-deficient children

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Sandro Loche

2014-03-01

Full Text Available Until 1985 growth hormone (GH was obtained from pituitary extracts, and was available in limited amounts only to treat severe growth hormone deficiency (GHD. With the availability of unlimited quantities of GH obtained from recombinant DNA technology, researchers started to explore new modalities to treat GHD children, as well as to treat a number of other non-GHD conditions. Although with some differences between different countries, GH treatment is indicated in children with Turner syndrome, chronic renal insufficiency, Prader-Willi syndrome, deletions/mutations of the SHOX gene, as well as in short children born small for gestational age and with idiopathic short stature. Available data from controlled trials indicate that GH treatment increases adult height in patients with Turner syndrome, in patients with chronic renal insufficiency, and in short children born small for gestational age. Patients with SHOX deficiency seem to respond to treatment similarly to Turner syndrome. GH treatment in children with idiopathic short stature produces a modest mean increase in adult height but the response in the individual patient is unpredictable. Uncontrolled studies indicate that GH treatment may be beneficial also in children with Noonan syndrome. In patients with Prader-Willi syndrome GH treatment normalizes growth and improves body composition and cognitive function. In any indication the response to GH seems correlated to the dose and the duration of treatment. GH treatment is generally safe with no major adverse effects being recorded in any condition.

Aged PROP1 deficient dwarf mice maintain ACTH production.

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Igor O Nasonkin

Full Text Available Humans with PROP1 mutations have multiple pituitary hormone deficiencies (MPHD that typically advance from growth insufficiency diagnosed in infancy to include more severe growth hormone (GH deficiency and progressive reduction in other anterior pituitary hormones, eventually including adrenocorticotropic hormone (ACTH deficiency and hypocortisolism. Congenital deficiencies of GH, prolactin, and thyroid stimulating hormone have been reported in the Prop1(null (Prop1(-/- and the Ames dwarf (Prop1(df/df mouse models, but corticotroph and pituitary adrenal axis function have not been thoroughly investigated. Here we report that the C57BL6 background sensitizes mutants to a wasting phenotype that causes approximately one third to die precipitously between weaning and adulthood, while remaining homozygotes live with no signs of illness. The wasting phenotype is associated with severe hypoglycemia. Circulating ACTH and corticosterone levels are elevated in juvenile and aged Prop1 mutants, indicating activation of the pituitary-adrenal axis. Despite this, young adult Prop1 deficient mice are capable of responding to restraint stress with further elevation of ACTH and corticosterone. Low blood glucose, an expected side effect of GH deficiency, is likely responsible for the elevated corticosterone level. These studies suggest that the mouse model differs from the human patients who display progressive hormone loss and hypocortisolism.

Growth retardation due to idiopathic growth hormone deficiencies: MR findings in 24 patients

International Nuclear Information System (INIS)

Ochi, M.; Morikawa, M.; Yoshimoto, M.; Kinoshita, E.; Hayashi, K.

1992-01-01

In this study we evaluated the pituitary-hypothalamic abnormalities of ''idiopathic growth hormone (GH) deficiency'' as demonstrated by MR imaging. Twenty-four patients were examined with a 1.5-T unit using spin echo T-1 weighted images. The patients were divided into two groups according to MR findings: those with ectopic posterior pituitary glands (12 patients), and those with normal posterior pituitary glands (12 patients). Ten patients in the former group and four in the latter group had small anterior pituitary glands. All patients in the former group but only four in the latter group had severe GH deficiencies. Multiple hormone deficiencies were found in eight patients in the former group, but in only two in the latter group. It is speculated that perinatal abnormalities can cause posterior pituitary ectopia and that there is a close correlation between breech delivery and the male disadvantage of posterior pituitary ectopia. Half of our patients with ''idiopathic GH deficiency'' had ectopic posterior pituitaries. GH deficiency with posterior pituitary ectopia should no longer be considered idiopathic because organic lesions can now be identified during life. (orig./GD)

Growth hormone (GH) provocative retesting of 108 young adults with childhood-onset GH deficiency and the diagnostic value of insulin-like growth factor I (IGF-I) and IGF-binding protein-3

DEFF Research Database (Denmark)

Juul, A; Kastrup, K W; Pedersen, S A

1997-01-01

.e. 45% of patients treated with GH during childhood because of isolated GHD had a normal GH response when retested in adulthood. Multiple regression analysis revealed that peak GH levels were dependent on the degree of hypopituitarism, body mass index, and duration of disease. IGF-I levels were below -2...

Immobilization of Glycoside Hydrolase Families GH1, GH13, and GH70: State of the Art and Perspectives

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Natália G. Graebin

2016-08-01

Full Text Available Glycoside hydrolases (GH are enzymes capable to hydrolyze the glycosidic bond between two carbohydrates or even between a carbohydrate and a non-carbohydrate moiety. Because of the increasing interest for industrial applications of these enzymes, the immobilization of GH has become an important development in order to improve its activity, stability, as well as the possibility of its reuse in batch reactions and in continuous processes. In this review, we focus on the broad aspects of immobilization of enzymes from the specific GH families. A brief introduction on methods of enzyme immobilization is presented, discussing some advantages and drawbacks of this technology. We then review the state of the art of enzyme immobilization of families GH1, GH13, and GH70, with special attention on the enzymes β-glucosidase, α-amylase, cyclodextrin glycosyltransferase, and dextransucrase. In each case, the immobilization protocols are evaluated considering their positive and negative aspects. Finally, the perspectives on new immobilization methods are briefly presented.

Two siblings with isolated GH deficiency due to loss-of-function mutation in the GHRHR gene: successful treatment with growth hormone despite late admission and severe growth retardation.

Science.gov (United States)

Sıklar, Zeynep; Berberoğlu, Merih; Legendre, Maria; Amselem, Serge; Evliyaoğlu, Olcay; Hacıhamdioğlu, Bülent; Savaş Erdeve, Senay; Oçal, Gönül

2010-01-01

Patients with growth hormone releasing hormone receptor (GHRHR) mutations exhibit pronounced dwarfism and are phenotypically and biochemically indistinguishable from other forms of isolated growth hormone deficiency (IGHD). We presented here two siblings with clinical findings of IGHD due to a nonsense mutation in the GHRHR gene who reached their target height in spite of late GH treatment. Two female siblings were admitted to our clinic with severe short stature at the age of 13.8 (patient 1) and 14.8 years (patient 2). On admission, height in patient 1 was 107 cm (-8.6 SD) and 117 cm (-6.7 SD) in patient 2. Bone age was delayed in both patients (6 years and 9 years). Clinical and biochemical analyses revealed a diagnosis of complete IGHD (peak GH levels on stimulation test was 0.06 ng/mL in patient 1 and 0.16 ng/mL in patient 2). Patients were given recombinant human GH treatment. Genetic analysis of the GH and GHRHR genes revealed that both patientscarried the GHRHR gene mutation p.Glu72X (c.214 G>T) in exon 3 in homozygous (or hemizygous) state. After seven years of GH treatment, the patients reached a final height appropriate for their target height. Final height was 151 cm (-1.5 SD) in patient 1 and 153 cm (-1.2 SD) in patient 2. In conclusion, genetic analysis is indicated in IGHD patients with severe growth failure and a positive family history. In spite of the very late diagnosis in these two patients who presented with severe growth deficit due to homozygous loss-of-function mutations in GHRHR, their final heights reached the target height.

Baraitser and Winter syndrome with growth hormone deficiency.

Science.gov (United States)

Chentli, Farida; Zellagui, Hadjer

2014-01-01

Baraitser-Winter syndrome (BWS), first reported in 1988, is apparently due to genetic abnormalities that are still not well-defined, although many gene abnormalities are already discovered and de novo missense changes in the cytoplasmic actin-encoding genes (called ACTB and ACTG1) have been recently discovered. The syndrome combines facial and cerebral malformations. Facial malformations totally or partially present in the same patient are: Iris coloboma, bilateral ptosis, hypertelorism, broad nasal bridge, and prominent epicanthic folds. The various brain malformations are probably responsible for growth and mental retardation. To the best of our knowledge, the syndrome is very rare as few cases have been reported so far. Our aim was to describe a child with a phenotype that looks like BWS with proved partial growth hormone (GH) deficiency which was not reported before. A girl aged 7-year-old of consanguineous parents was referred for short stature and mental retardation. Clinical examination showed dwarfism and a delay in her mental development. Other clinical features included: Strabismus, epicanthic folds, broad nasal bridge, and brain anomalies such as lissencephaly, bilateral hygroma, and cerebral atrophy. Hormonal assessment showed partial GH deficiency without other endocrine disorders. Our case looks exactly like BWS. However, apart from facial and cerebral abnormalities, there is a partial GH deficiency which can explain the harmonious short stature. This case seems worth to be reported as it adds GH deficiency to the very rare syndrome.

strong>A novel oral preparation of human growth hormone (hGH) is absorbed and increases serum IGF-I levels after 7 days administration to GH-deficient adultsstrong>

DEFF Research Database (Denmark)

Laursen, Torben; Mindeholm, Linda; Haemmerle, Sibylle

2007-01-01

) as carrier has recently been developed. The aim of this study was to determine if this oral formulation of hGH could be absorbed and be bioactive. Eight GHD men (mean age 50 years) receiving sc hGH therapy were withdrawn from therapy for 7 days and then treated for 7 days orally with tablets of HGH191...

Is increase in bone mineral content caused by increase in skeletal muscle mass/strength in adult patients with GH-treated GH deficiency? A systematic literature analysis

DEFF Research Database (Denmark)

Klefter, O.; Feldt-Rasmussen, U.

2009-01-01

to a muscle modulating effect, and if treatment with GH would primarily increase muscle mass and strength with a secondary increase in BMD/BMC, thus supporting the present physiological concept that mass and strength of bones are mainly determined by dynamic loads from the skeletal muscles. METHOD: We...... performed a systematic literature analysis, including 51 clinical trials published between 1996 and 2008, which had studied the development in muscle mass, muscle strength, BMD, and/or BMC in GH-treated adult GHD patients. RESULTS: GH therapy had an anabolic effect on skeletal muscle. The largest increase...... in muscle mass occurred during the first 12 months of therapy. Most trials measuring BMD/BMC reported significant increases from baseline values. The significant increases in BMD/BMC occurred after 12-18 months of treatment, i.e. usually later than the increases in muscle parameters. Only seven trials...

Low prevalence of hypopituitarism after subarachnoid haemorrhage using confirmatory testing and with BMI-specific GH cut-off levels.

Science.gov (United States)

Gardner, Chris J; Javadpour, Mohsen; Stoneley, Catherine; Purthuran, Mani; Biswas, Shubhabrata; Daousi, Christina; MacFarlane, Ian A; Cuthbertson, Daniel J

2013-04-01

Hypopituitarism following subarachnoid haemorrhage (SAH) has been reported to be a frequent occurrence. However, there is considerable heterogeneity between studies with differing patient populations and treatment modalities and most importantly employing differing endocrine protocols and (normal) reference ranges of GH. We aimed to examine prospectively a cohort of SAH survivors for development of hypopituitarism post-SAH using rigorous endocrine testing and compare GH response to glucagon stimulation with a cohort of healthy controls of a similar BMI. Sixty-four patients were investigated for evidence of hypopituitarism 3 months post-SAH with 50 patients tested again at 12 months. Glucagon stimulation testing (GST), with confirmation of deficiencies by GHRH/arginine testing for GH deficiency (GHD) and short synacthen testing for ACTH deficiency, was used. Basal testing of other hormonal axes was undertaken. Mean age of patients was 53±11.7 years and mean BMI was 27.5±5.7 kg/m(2). After confirmatory testing, the prevalence of hypopituitarism was 12% (GHD 10%, asymptomatic hypocortisolaemia 2%). There was no association between hypopituitarism and post-SAH vasospasm, presence of cerebral infarction, Fisher grade, or clinical grading at presentation. There was a significant correlation between BMI and peak GH to glucagon stimulation in both patients and controls. Identification of 'true' GHD after SAH requires confirmatory testing with an alternative stimulation test and application of BMI-specific cut-offs. Using such stringent criteria, we found a prevalence of hypopituitarism of 12% in our population.

Cognitive impairments and mood disturbances in growth hormone deficient men

NARCIS (Netherlands)

Deijen, J.B.; de Boer, H.; Blok, G.J.; van der Veen, E.A.

1996-01-01

In order to establish whether reported psychological complaints in hypopituitary adults are related to growth hormone (GH) deficiency or other pituitary hormone deficiencies, emotional well-being and cognitive performance were evaluated in 31 men with multiple pituitary hormone deficiencies (MPHD)

Growth hormone deficiency in children and young adults.

Science.gov (United States)

Oświęcimska, Joanna; Roczniak, Wojciech; Mikołajczak, Agata; Szymlak, Agnieszka

2016-09-13

Growth hormone (GH) is a naturally occurring polypeptide hormone produced by somatotropic cells in the anterior pituitary. The main function of somatotropin is stimulation of linear growth, but it also affects carbohydrate metabolism, increases bone mass and has potent lipolytic, antinatriuretic and antidiuretic effects. Growth hormone deficiency (GHD) may occur both in children and in adults. At the moment there is no gold standard for the diagnosis of GHD, and the diagnosis should take into account clinical, auxological, biochemical and radiological changes and, if necessary, genetic testing. Recent studies have highlighted that the biochemical diagnosis of GH deficiency is still imperfect. Stimuli used in the tests are non-physiological, and various substances are characterized by a different mechanism of action and potency. A few years ago it was thought that GHD treatment in children must be completed at the end of linear growth. Studies performed in the last two decades have shown that GHD deficiency in adults may result in complex clinical problems, and if untreated shortens the life expectancy and worsens its comfort. Discontinuation of GH therapy after the final height has been reached in fact negatively impacts the physiological processes associated with the transition phase, which is the period of human life between achieving the final height and 25-30 years of age. Given the adverse metabolic effects of GH treatment interruption after linear growth has been completed, the latest recommendations propose reassessment of GH secretion in the period at least one month after cessation of treatment and continuation of the therapy in case of persistent deficit.

Growth hormone deficiency in children and young adults

Directory of Open Access Journals (Sweden)

Joanna Oświęcimska

2016-09-01

Full Text Available Growth hormone (GH is a naturally occurring polypeptide hormone produced by somatotropic cells in the anterior pituitary. The main function of somatotropin is stimulation of linear growth, but it also affects carbohydrate metabolism, increases bone mass and has potent lipolytic, antinatriuretic and antidiuretic effects. Growth hormone deficiency (GHD may occur both in children and in adults. At the moment there is no gold standard for the diagnosis of GHD, and the diagnosis should take into account clinical, auxological, biochemical and radiological changes and, if necessary, genetic testing. Recent studies have highlighted that the biochemical diagnosis of GH deficiency is still imperfect. Stimuli used in the tests are non-physiological, and various substances are characterized by a different mechanism of action and potency. A few years ago it was thought that GHD treatment in children must be completed at the end of linear growth. Studies performed in the last two decades have shown that GHD deficiency in adults may result in complex clinical problems, and if untreated shortens the life expectancy and worsens its comfort. Discontinuation of GH therapy after the final height has been reached in fact negatively impacts the physiological processes associated with the transition phase, which is the period of human life between achieving the final height and 25-30 years of age. Given the adverse metabolic effects of GH treatment interruption after linear growth has been completed, the latest recommendations propose reassessment of GH secretion in the period at least one month after cessation of treatment and continuation of the therapy in case of persistent deficit.

Ames dwarf (Prop1(df)/Prop1(df)) mice display increased sensitivity of the major GH-signaling pathways in liver and skeletal muscle.

Science.gov (United States)

Miquet, Johanna G; Muñoz, Marina C; Giani, Jorge F; González, Lorena; Dominici, Fernando P; Bartke, Andrzej; Turyn, Daniel; Sotelo, Ana I

2010-04-01

Growth hormone (GH) is an anabolic hormone that regulates growth and metabolism. Ames dwarf mice are natural mutants for Prop1, with impaired development of anterior pituitary and undetectable levels of circulating GH, prolactin and TSH. They constitute an endocrine model of life-long GH-deficiency. The main signaling cascades activated by GH binding to its receptor are the JAK2/STATs, PI-3K/Akt and the MAPK Erk1/2 pathways. We have previously reported that GH-induced STAT5 activation was higher in Ames dwarf mice liver compared to non-dwarf controls. The aim of this study was to evaluate the principal components of the main GH-signaling pathways under GH-deficiency in liver and skeletal muscle, another GH-target tissue. Ames dwarf mice and their non-dwarf siblings were assessed. Animals were injected i.p. with GH or saline 15min before tissue removal. Protein content and phosphorylation of signaling mediators were determined by immunoblotting of tissue solubilizates. GH was able to induce STAT5 and STAT3 tyrosine phosphorylation in both liver and muscle, but the response was higher for Ames dwarf mice than for non-dwarf controls. When Erk1/2 activation was assessed in liver, only dwarf mice showed GH-induced phosphorylation, while in muscle no response to the hormone was found in either genotype. GH-induced Akt phosphorylation at Ser473 in liver was only detected in dwarf mice. In skeletal muscle, both normal and dwarf mice responded to a GH stimulus, although dwarf mice presented higher GH activation levels. The phosphorylation of GSK-3, a substrate of Akt, increased upon hormone stimulation only in dwarf mice in both tissues. In contrast, no differences in the phosphorylation of mTOR, another substrate of Akt, were observed after GH stimulus, either in normal or dwarf mice in liver, while we were unable to determine mTOR in muscle. Protein content of GH-receptor and of the signaling mediators studied did not vary between normal and dwarf animals in the assessed

Long-term effects of continuous subcutaneous infusion versus daily subcutaneous injections of growth hormone (GH) on the insulin-like growth factor system, insulin sensitivity, body composition, and bone and lipoprotein metabolism in GH-deficient adults

DEFF Research Database (Denmark)

Laursen, Torben; Gravholt, Claus Højbjerg; Heickendorff, Lene

2001-01-01

injections (inj) in the evening as usual, and 7 received a continuous infusion (inf) of GH by means of a portable pump. The GH dose was kept unchanged before and during the study. Serum levels of insulin-like growth factor I (IGF-I) tended to increase in the patients switched to constant infusion (from 175...... for 6 months are comparable with respect to the IGF-IGFBP axis, whereas intermittent exposure may be of importance for the lipolytic effect of GH. The data on insulin sensitivity and lipoproteins suggest that constant GH exposure is as safe as intermittent GH administration....

GH and IGF1: Roles in Energy Metabolism of Long-Living GH Mutant Mice

OpenAIRE

Brown-Borg, Holly M.; Bartke, Andrzej

2012-01-01

Of the multiple theories to explain exceptional longevity, the most robust of these has centered on the reduction of three anabolic protein hormones, growth hormone (GH), insulin-like growth factor, and insulin. GH mutant mice live 50% longer and exhibit significant differences in several aspects of energy metabolism as compared with wild-type mice. Mitochondrial metabolism is upregulated in the absence of GH, whereas in GH transgenic mice and dwarf mice treated with GH, multiple aspects of t...

Continuation of growth hormone therapy versus placebo in transition-phase patients with growth hormone deficiency

DEFF Research Database (Denmark)

Jørgensen, Jens; Nørrelund, Helene; Vahl, Nina

2002-01-01

In a placebo-controlled, parallel study of 18 patients with a mean age of 20 years who had confirmed growth hormone (GH) deficiency, we evaluated body composition, insulin sensitivity, and glucose turnover at baseline (when all were receiving GH replacement); after 12 months of continued GH therapy...

Circulating growth hormone (GH)-binding protein complex: a major constituent of plasma GH in man

International Nuclear Information System (INIS)

Baumann, G.; Amburn, K.; Shaw, M.A.

1988-01-01

The recent discovery of a specific binding protein for human GH (hGH) in human plasma suggests that hGH circulates in part as a complex in association with the binding protein(s). However, the magnitude of the complexed fraction prevailing under physiological conditions is unknown because of 1) dissociation of the complex during analysis and 2) potential differences in the binding characteristics of radiolabeled and native hGH. We conducted experiments designed to minimize dissociation during analysis (gel filtration in prelabeled columns, frontal analysis, and batch molecular sieving) with both native and radioiodinated hGH. All three methods yielded similar estimates for the complexed fraction. In normal plasma the bound fraction for 22 K hGH averaged 50.1% (range, 39-59%), that for 20 K hGH averaged 28.5% (range, 26-31%). Above a hGH level of about 20 ng/ml the bound fraction declines in concentration-dependent manner due to saturation of the binding protein. We conclude that a substantial part of circulating hGH is complexed with carrier proteins. This concept has important implications for the metabolism, distribution, and biological activity of hGH

Endothelin-1-induced focal cerebral ischemia in the growth hormone/IGF-1 deficient Lewis Dwarf rat.

Science.gov (United States)

Yan, Han; Mitschelen, Matthew; Toth, Peter; Ashpole, Nicole M; Farley, Julie A; Hodges, Erik L; Warrington, Junie P; Han, Song; Fung, Kar-Ming; Csiszar, Anna; Ungvari, Zoltan; Sonntag, William E

2014-11-01

Aging is a major risk factor for cerebrovascular disease. Growth hormone (GH) and its anabolic mediator, insulin-like growth factor (IGF)-1, decrease with advancing age and this decline has been shown to promote vascular dysfunction. In addition, lower GH/IGF-1 levels are associated with higher stroke mortality in humans. These results suggest that decreased GH/IGF-1 level is an important factor in increased risk of cerebrovascular diseases. This study was designed to assess whether GH/IGF-1-deficiency influences the outcome of cerebral ischemia. We found that endothelin-1-induced middle cerebral artery occlusion resulted in a modest but nonsignificant decrease in cerebral infarct size in GH/IGF-1 deficient dw/dw rats compared with control heterozygous littermates and dw/dw rats with early-life GH treatment. Expression of endothelin receptors and endothelin-1-induced constriction of the middle cerebral arteries were similar in the three experimental groups. Interestingly, dw/dw rats exhibited reduced brain edema and less astrocytic infiltration compared with their heterozygous littermates and this effect was reversed by GH-treatment. Because reactive astrocytes are critical for the regulation of poststroke inflammatory processes, maintenance of the blood-brain barrier and neural repair, further studies are warranted to determine the long-term functional consequences of decreased astrocytic activation in GH/IGF-1 deficient animals after cerebral ischemia. Published by Oxford University Press on behalf of the Gerontological Society of America 2014.

Growth hormone (GH)-releasing activity of chicken GH-releasing hormone (GHRH) in chickens.

Science.gov (United States)

Harvey, S; Gineste, C; Gaylinn, B D

2014-08-01

Two peptides with sequence similarities to growth hormone releasing hormone (GHRH) have been identified by analysis of the chicken genome. One of these peptides, chicken (c) GHRH-LP (like peptide) was previously found to poorly bind to chicken pituitary membranes or to cloned and expressed chicken GHRH receptors and had little, if any, growth hormone (GH)-releasing activity in vivo or in vitro. In contrast, a second more recently discovered peptide, cGHRH, does bind to cloned and expressed cGHRH receptors and increases cAMP activity in transfected cells. The possibility that this peptide may have in vivo GH-releasing activity was therefore assessed. The intravenous (i.v.) administration of cGHRH to immature chickens, at doses of 3-100 μg/kg, significantly increased circulating GH concentrations within 10 min of injection and the plasma GH levels remained elevated for at least 30 min after the injection of maximally effective doses. The plasma GH responses to cGHRH were comparable with those induced by human (h) or porcine (p) GHRH preparations and to that induced by thyrotropin releasing hormone (TRH). In marked contrast, the i.v. injection of cGHRH-LP had no significant effect on circulating GH concentrations in immature chicks. GH release was also increased from slaughterhouse chicken pituitary glands perifused for 5 min with cGHRH at doses of 0.1 μg/ml or 1.0 μg/ml, comparable with GH responses to hGHRH1-44. In contrast, the perifusion of chicken pituitary glands with cGHRH-LP had no significant effect on GH release. In summary, these results demonstrate that cGHRH has GH-releasing activity in chickens and support the possibility that it is the endogenous ligand of the cGHRH receptor. Copyright © 2014 Elsevier Inc. All rights reserved.

Long-Term Outcomes, Genetics, and Pituitary Morphology in Patients with Isolated Growth Hormone Deficiency and Multiple Pituitary Hormone Deficiencies: A Single-Centre Experience of Four Decades of Growth Hormone Replacement.

Science.gov (United States)

Rohayem, Julia; Drechsel, Hendrik; Tittel, Bettina; Hahn, Gabriele; Pfaeffle, Roland; Huebner, Angela

2016-01-01

Growth hormone (GH) has been used to treat children with GH deficiency (GHD) since 1966. Using a combined retrospective and cross-sectional approach, we explored the long-term outcomes of patients with GHD, analysed factors influencing therapeutic response, determined persistence into adulthood, investigated pituitary morphology, and screened for mutations in causative genes. The files of 96 GH-deficient children were reviewed. In a subset of 50 patients, re-assessment in adulthood was performed, including GHRH-arginine testing, pituitary magnetic resonance imaging (MRI), and mutational screening for the growth hormone-1 gene (GH1) and the GHRH receptor gene (GHRHR) in isolated GHD (IGHD), and HESX1, PROP1, POU1F1, LHX3, LHX4, and GLI2 in multiple pituitary hormone deficiency (MPHD) patients. GH was started at a height SDS of -3.2 ± 1.4 in IGHD patients and of -4.1 ± 2.1 in MPHD patients. Relative height gain was 0.3 SDS/year, absolute gain 1.6 SDS, and 1.2/2.6 SDS in IGHD/MPHD, respectively. Mid-parental target height was reached in 77%. Initial height SDS, bone age retardation and duration of GH replacement were correlated with height SDS gain. GHD persisted into adulthood in 19 and 89% of subjects with IGHD and MPHD, respectively. In 1/42 IGHD patients a GH1 mutation was detected; PROP1 mutations were found in 3/7 MPHD subjects. Anterior pituitary hypoplasia, combined with posterior pituitary ectopy and pituitary stalk invisibility on MRI, was an exclusive finding in MPHD patients. GH replacement successfully corrects the growth deficit in children with GHD. While the genetic aetiology remains undefined in most cases of IGHD, PROP1 mutations constitute a major cause for MPHD. Persistence of GHD into adulthood is related to abnormal pituitary morphology. © 2016 S. Karger AG, Basel.

The growth hormone (GH) response to GH-releasing peptide (His-DTrp-Ala-Trp-DPhe-Lys-NH2), GH-releasing hormone, and thyrotropin-releasing hormone in acromegaly.

Science.gov (United States)

Alster, D K; Bowers, C Y; Jaffe, C A; Ho, P J; Barkan, A L

1993-09-01

In patients with acromegaly, GH-producing pituitary tumors release GH in response to specific stimuli such as GH-releasing hormone (GHRH) and are also responsive to a variety of nonspecific stimuli, such as TRH or GnRH, and may exhibit paradoxical responses to glucose and dopamine. In healthy humans, the synthetic peptide GH-releasing peptide (GHRP) (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) releases GH by a putative mechanism of action that is independent of GHRH. How these tumors respond to GHRP is not well characterized. We studied the GH responses to GHRH, GHRP, and TRH stimulation in 11 patients with active acromegaly. The peak GH responses to GHRP and GHRH were not correlated (r = 0.57; P = 0.066). In contrast, the peak GH responses to GHRP and TRH were highly correlated (r = 0.95; P < 0.001). In conclusion, in patients with acromegaly, the GH response to GHRP is qualitatively normal and does not appear to depend on GHRH.

Progression from isolated growth hormone deficiency to combined pituitary hormone deficiency.

Science.gov (United States)

Cerbone, Manuela; Dattani, Mehul T

2017-12-01

Growth hormone deficiency (GHD) can present at any time of life from the neonatal period to adulthood, as a result of congenital or acquired insults. It can present as an isolated problem (IGHD) or in combination with other pituitary hormone deficiencies (CPHD). Pituitary deficits can evolve at any time from GHD diagnosis. The number, severity and timing of occurrence of additional endocrinopathies are highly variable. The risk of progression from IGHD to CPHD in children varies depending on the etiology (idiopathic vs organic). The highest risk is displayed by children with abnormalities in the Hypothalamo-Pituitary (H-P) region. Heterogeneous data have been reported on the type and timing of onset of additional pituitary hormone deficits, with TSH deficiency being most frequent and Diabetes Insipidus the least frequent additional deficit in the majority, but not all, of the studies. ACTH deficiency may gradually evolve at any time during follow-up in children or adults with childhood onset IGHD, particularly (but not only) in presence of H-P abnormalities and/or TSH deficiency. Hence there is a need in these patients for lifelong monitoring for ACTH deficiency. GH treatment unmasks central hypothyroidism mainly in patients with organic GHD, but all patients starting GH should have their thyroid function monitored closely. Main risk factors for development of CPHD include organic etiology, H-P abnormalities (in particular pituitary stalk abnormalities, empty sella and ectopic posterior pituitary), midline brain (corpus callosum) and optic nerves abnormalities, genetic defects and longer duration of follow-up. The current available evidence supports longstanding recommendations for the need, in all patients diagnosed with IGHD, of a careful and indefinite follow-up for additional pituitary hormone deficiencies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Microarchitecture, but Not Bone Mechanical Properties, Is Rescued with Growth Hormone Treatment in a Mouse Model of Growth Hormone Deficiency

OpenAIRE

Kristensen, Erika; Hallgrímsson, Benedikt; Morck, Douglas W.; Boyd, Steven K.

2012-01-01

Growth hormone (GH) deficiency is related to an increased fracture risk although it is not clear if this is due to compromised bone quality or a small bone size. We investigated the relationship between bone macrostructure, microarchitecture and mechanical properties in a GH-deficient (GHD) mouse model undergoing GH treatment commencing at an early (prepubertal) or late (postpubertal) time point. Microcomputed tomography images of the femur and L4 vertebra were obtained to quantify macrostruc...

Agenesis of internal carotid artery associated with isolated growth hormone deficiency: a case report and literature review.

Science.gov (United States)

Stagi, Stefano; Traficante, Giovanna; Lapi, Elisabetta; Pantaleo, Marilena; Becciani, Sabrina; Mortilla, Marzia; Seminara, Salvatore; de Martino, Maurizio

2015-10-19

Agenesis of the internal carotid artery (ICA) is a rare congenital abnormality, sporadically reported to be associated with a combined congenital hypopituitarism. Nevertheless, only a few cases have been extensively described, and none of these have been characterized by an isolated growth hormone (GH) deficiency. Here, we describe a 17-year old boy referred to our hospital for fatigue, decreased muscle strength and severe headache reported after the cessation of rhGH treatment for a GH deficiency diagnosed at the age of 2 years and 3 months. Magnetic resonance imaging (MRI) showed an adenohypophyseal hypoplasia with a lack of posterior pituitary hyperintensity, whereas MRI angiography indicated the absence of a normal flow void in the left ICA. Endocrinological tests confirmed the GH deficiency (GH peak after growth-hormone-releasing hormone (GHRH) + arginine: 2.42 ng/mL) with a very low IGF-I value (31 ng/mL) and normal function of other pituitary axes. To the best of our knowledge this is the first confirmed case of an isolated GH deficiency in a patient with ICA agenesis. The presence of an isolated pituitary deficit is unlike to be considered only as an effect of hemodynamic mechanism, suggesting a role for genetic factor(s) as a common cause of these two rare birth defects. Further studies could clarify this issue and the underlying mechanisms to better understand the etiopathogenetic characteristics of this disorder.

Biphasic response of subscapular skinfold thickness to hGH or IGF-1 administration to patients with congenital IGHD, congenital MPHD and Laron syndrome.

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Bisker-Kassif, Orly; Kauli, Rivka; Lilos, Pearl; Laron, Zvi

2014-01-01

To evaluate changes in adiposity in congenital GH/IGF-1 deficient children during hGH or IGF-1 treatment. 27 children with congenital isolated growth hormone deficiency (cIGHD) treated with hGH for 2.5-€“15.2 years (mean 10.0 ± 3.4), 18 children with congenital multiple pituitary hormone deficiency (cMPHD), treated with hGH for 2.3-€“17.9 years (mean 6.1 ± 4.3), and 14 children with Laron syndrome (LS) treated with IGF-1 for 1.2-12 years (mean 5.5 ± 3.7) were studied. Changes in the degree of adiposity were evaluated by subscapular skinfold thickness (SSFT), before, during and up to 2 years after treatment. All the children had various degrees of obesity. During the pretreatment period, cIGHD patients showed little changes in SSFT (P = 0.45), cMPHD and LS patients showed an increase in SSFT (P = 0.01, P = 0.06 respectively). During the initial 0.6-1.1 years of hGH/IGF-1 treatment, the SSFT decreased in all 3 groups (P < 0.001), while during subsequent years a significant increase in SSFT (P < 0.001) was observed, in all types of patients, notably in females. Only the cIGHD patients demonstrated a significant correlation between the degree of SSFT decrease and height SDS gain (R = -ˆ’0.56, P = 0.002) in the first period of treatment. Short term replacement therapy of 0.6-€“1.1 years with either hGH or IGF-1, induced a reduction in subscapular subcutaneous fat whereas prolongation of therapy led to an increase in the subcutaneous fat. © 2014 Asian Oceanian Association for the Study of Obesity . Published by Elsevier Ltd. All rights reserved.

New diagnostic tests of GH reserve.

Science.gov (United States)

Martul, P; Pineda, J; Pombo, M; Peñalva, A; Bokser, L; Dieguez, C

1993-01-01

Pharmacological tests are essential for the diagnosis of growth hormone (GH) insufficiency. Obesity is a pathological state associated with blunted GH response to all the classical stimuli tested. In the present study, three new pharmacological stimuli for GH reserve were evaluated in three groups of subjects: Normal, GH-insufficient and normal growing obese children. Dexamethasone provokes a clear GH-response in normal children, whereas the response in the other 2 groups of patients is significantly diminished. Galanin-induced GH-secretion is significantly higher in normal than in obese children. GHRP-6 causes a potent GH release in normal children, higher than in GH-insufficiency or obesity. The overlap shown between GH-insufficient patients and normal children reduces the usefulness of the tests. Similar to the classical stimuli, the response to these new tests is also decreased in obesity.

Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice.

Science.gov (United States)

Csiszar, Anna; Labinskyy, Nazar; Perez, Viviana; Recchia, Fabio A; Podlutsky, Andrej; Mukhopadhyay, Partha; Losonczy, Gyorgy; Pacher, Pal; Austad, Steven N; Bartke, Andrzej; Ungvari, Zoltan

2008-11-01

Hypopituitary Ames dwarf mice have low circulating growth hormone (GH)/IGF-I levels, and they have extended longevity and exhibit many symptoms of delayed aging. To elucidate the vascular consequences of Ames dwarfism we compared endothelial O2(-) and H2O2 production, mitochondrial reactive oxygen species (ROS) generation, expression of antioxidant enzymes, and nitric oxide (NO) production in aortas of Ames dwarf and wild-type control mice. In Ames dwarf aortas endothelial O2(-) and H2O2 production and ROS generation by mitochondria were enhanced compared with those in vessels of wild-type mice. In Ames dwarf aortas there was a less abundant expression of Mn-SOD, Cu,Zn-SOD, glutathione peroxidase (GPx)-1, and endothelial nitric oxide synthase (eNOS). NO production and acetylcholine-induced relaxation were also decreased in aortas of Ames dwarf mice. In cultured wild-type mouse aortas and in human coronary arterial endothelial cells treatment with GH and IGF significantly reduced cellular O2(-) and H2O2 production and ROS generation by mitochondria and upregulated expression of Mn-SOD, Cu,Zn-SOD, GPx-1, and eNOS. Thus GH and IGF-I promote antioxidant phenotypic changes in the endothelial cells, whereas Ames dwarfism leads to vascular oxidative stress.

A remote but significant sequence homology between glycoside hydrolase clan GH-H and glycoside hydrolase family GH 31

DEFF Research Database (Denmark)

Janecek, S.; Svensson, Birte; MacGregor, E.A.

2007-01-01

Although both the α-amylase super-family, i.e. the glycoside hydrolase (GH) clan GH-H (the GH families 13, 70 and 77), and family GH31 share some characteristics, their different catalytic machinery prevents classification of GH31 in clan GH-H. A significant but remote evolutionary relatedness is...

Growth hormone and IGF-1 deficiency exacerbate high-fat diet-induced endothelial impairment in obese Lewis dwarf rats: implications for vascular aging.

Science.gov (United States)

Bailey-Downs, Lora C; Sosnowska, Danuta; Toth, Peter; Mitschelen, Matthew; Gautam, Tripti; Henthorn, Jim C; Ballabh, Praveen; Koller, Akos; Farley, Julie A; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

2012-06-01

Previous studies suggest that the age-related decline in circulating growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels significantly contribute to vascular dysfunction in aging by impairing cellular oxidative stress resistance pathways. Obesity in elderly individuals is increasing at alarming rates, and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging, GH/IGF-1 deficiency, and obesity interact to promote the development of cardiovascular disease remain unclear. To test the hypothesis that low circulating GH/IGF-1 levels exacerbate the pro-oxidant and proinflammatory vascular effects of obesity, GH/IGF-1-deficient Lewis dwarf rats and heterozygous control rats were fed either a standard diet or a high-fat diet (HFD) for 7 months. Feeding an HFD resulted in similar relative weight gains and increases in body fat content in Lewis dwarf rats and control rats. HFD-fed Lewis dwarf rats exhibited a relative increase in blood glucose levels, lower insulin, and impaired glucose tolerance as compared with HFD-fed control rats. Analysis of serum cytokine expression signatures indicated that chronic GH/IGF-1 deficiency exacerbates HFD-induced inflammation. GH/IGF-1 deficiency also exacerbated HFD-induced endothelial dysfunction, oxidative stress, and expression of inflammatory markers (tumor necrosis factor-α, ICAM-1) in aortas of Lewis dwarf rats. Overall, our results are consistent with the available clinical and experimental evidence suggesting that GH/IGF-1 deficiency renders the cardiovascular system more vulnerable to the deleterious effects of obesity.

Growth hormone deficiency in the transition period: body composition and gonad function.

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Balercia, G; Giovannini, L; Paggi, F; Spaziani, M; Tahani, N; Boscaro, M; Lenzi, A; Radicioni, A

2011-10-01

Recombinant GH therapy is normally administered to GH-deficient children in order to achieve a satisfactory height - the main target during childhood and adolescence. However, the role of GH does not end once final height has been reached, but continues during the so-called transition period. In this phase of life, the body undergoes several changes, both physical and psychological, that culminate in adulthood. During this period, GH has a part in numerous metabolic functions. These include the lipid profile, where it increases HDL and reduces LDL, with the global effect of cardiovascular protection. It also has important effects on body composition (improved muscle strength and lean body mass and reduced body fat), the achievement of proper peak bone density, and gonad maturation. Retesting during the transition period, involving measurement of IGF-I plus a provocative test (insulin tolerance test or GHRH + arginine test), is thus necessary to establish any persistent GH deficiency requiring additional replacement therapy. The close cooperation of the medical professionals involved in the patient's transition from a pediatric to an adult endocrinologist is essential. The aim of this review is to point out the main aspects of GH treatment on body composition, metabolic and gonad functions in the transition period.

GH and IGF1: roles in energy metabolism of long-living GH mutant mice.

Science.gov (United States)

Brown-Borg, Holly M; Bartke, Andrzej

2012-06-01

Of the multiple theories to explain exceptional longevity, the most robust of these has centered on the reduction of three anabolic protein hormones, growth hormone (GH), insulin-like growth factor, and insulin. GH mutant mice live 50% longer and exhibit significant differences in several aspects of energy metabolism as compared with wild-type mice. Mitochondrial metabolism is upregulated in the absence of GH, whereas in GH transgenic mice and dwarf mice treated with GH, multiple aspects of these pathways are suppressed. Core body temperature is markedly lower in dwarf mice, yet whole-body metabolism, as measured by indirect calorimetry, is surprisingly higher in Ames dwarf and Ghr-/- mice compared with normal controls. Elevated adiponectin, a key antiinflammatory cytokine, is also very likely to contribute to longevity in these mice. Thus, several important components related to energy metabolism are altered in GH mutant mice, and these differences are likely critical in aging processes and life-span extension.

Change in Serum Lipid during Growth Hormone Therapy in a Growth Hormone-Deficient Patient with Decreased Serum Apolipoprotem C-II

OpenAIRE

Tadashi, Moriwake; Masanori, Takaiwa; Masako, Kawakami; Shouichi, Tanaka; Tetsuya, Nakamura; Department of Pediatrics, Iwakuni National Hospital; Department of Pediatrics, Iwakuni National Hospital; Department of Pediatrics, Iwakuni National Hospital; Department of Internal Medicine, Iwakuni National Hospital; Department of Radiology, Iwakuni National Hospital

2003-01-01

Introduction The effects of GH on lipid metabolism have been discussed frequently in relation to quality of adult life in childhood-onset GH deficiency, but its effects on lipid metabolism were not fully understood. In the present study, we analyzed the longitudinal change in serum lipid metabolites and apolipoproteins in a GH-deficient patient who had a history of cholelithiasis with decreased apolipoprotein C-II. Case K.Y. Four-year old boy visited the emergency clinic of Iwakuni National H...

Acute hyperglycemia produces transient improvement in glucose transporter type 1 deficiency.

Science.gov (United States)

Akman, Cigdem I; Engelstad, Kristin; Hinton, Veronica J; Ullner, Paivi; Koenigsberger, Dorcas; Leary, Linda; Wang, Dong; De Vivo, Darryl C

2010-01-01

Glucose transporter type 1 deficiency syndrome (Glut1-DS) is characterized clinically by acquired microcephaly, infantile-onset seizures, psychomotor retardation, choreoathetosis, dystonia, and ataxia. The laboratory signature is hypoglycorrhachia. The 5-hour oral glucose tolerance test (OGTT) was performed to assess cerebral function and systemic carbohydrate homeostasis during acute hyperglycemia, in the knowledge that GLUT1 is constitutively expressed ubiquitously and upregulated in the brain. Thirteen Glut1-DS patients completed a 5-hour OGTT. Six patients had prolonged electroencephalographic (EEG)/video monitoring, 10 patients had plasma glucose and serum insulin measurements, and 5 patients had repeated measures of attention, memory, fine motor coordination, and well-being. All patients had a full neuropsychological battery prior to OGTT. The glycemic profile and insulin response during the OGTT were normal. Following the glucose load, transient improvement of clinical seizures and EEG findings were observed, with the most significant improvement beginning within the first 30 minutes and continuing for 180 minutes. Thereafter, clinical seizures returned, and EEG findings worsened. Additionally, transient improvement in attention, fine motor coordination, and reported well-being were observed without any change in memory performance. This study documents transient neurological improvement in Glut1-DS patients following acute hyperglycemia, associated with improved fine motor coordination and attention. Also, systemic carbohydrate homeostasis was normal, despite GLUT1 haploinsufficiency, confirming the specific role of GLUT1 as the transporter of metabolic fuel across the blood-brain barrier. The transient improvement in brain function underscores the rate-limiting role of glucose transport and the critical minute-to-minute dependence of cerebral function on fuel availability for energy metabolism.

Growth Hormone Research Society perspective on biomarkers of GH action in children and adults.

Science.gov (United States)

Johannsson, Gudmundur; Bidlingmaier, Martin; Biller, Beverly M K; Boguszewski, Margaret; Casanueva, Felipe F; Chanson, Philippe; Clayton, Peter E; Choong, Catherine S; Clemmons, David; Dattani, Mehul; Frystyk, Jan; Ho, Ken; Hoffman, Andrew R; Horikawa, Reiko; Juul, Anders; Kopchick, John J; Luo, Xiaoping; Neggers, Sebastian; Netchine, Irene; Olsson, Daniel S; Radovick, Sally; Rosenfeld, Ron; Ross, Richard J; Schilbach, Katharina; Solberg, Paulo; Strasburger, Christian; Trainer, Peter; Yuen, Kevin C J; Wickstrom, Kerstin; Jorgensen, Jens O L

2018-03-01

The Growth Hormone Research Society (GRS) convened a Workshop in 2017 to evaluate clinical endpoints, surrogate endpoints and biomarkers during GH treatment of children and adults and in patients with acromegaly. GRS invited 34 international experts including clinicians, basic scientists, a regulatory scientist and physicians from the pharmaceutical industry. Current literature was reviewed and expert opinion was utilized to establish the state of the art and identify current gaps and unmet needs. Following plenary presentations, breakout groups discussed questions framed by the planning committee. The attendees re-convened after each breakout session to share the group reports. A writing team compiled the breakout session reports into a document that was subsequently discussed and revised by participants. This was edited further and circulated for final review after the meeting. Participants from pharmaceutical companies were not part of the writing process. The clinical endpoint in paediatric GH treatment is adult height with height velocity as a surrogate endpoint. Increased life expectancy is the ideal but unfeasible clinical endpoint of GH treatment in adult GH-deficient patients (GHDA) and in patients with acromegaly. The pragmatic clinical endpoints in GHDA include normalization of body composition and quality of life, whereas symptom relief and reversal of comorbidities are used in acromegaly. Serum IGF-I is widely used as a biomarker, even though it correlates weakly with clinical endpoints in GH treatment, whereas in acromegaly, normalization of IGF-I may be related to improvement in mortality. There is an unmet need for novel biomarkers that capture the pleiotropic actions of GH in relation to GH treatment and in patients with acromegaly. © 2018 Growth Hormone Research Society.

The GH/IGF-I axis and pituitary function and size in adults with Prader-Willi syndrome

NARCIS (Netherlands)

van Nieuwpoort, I.C.; Sinnema, M.; Castelijns, J.A.; Twisk, J.W.; Curfs, L.M.; Drent, M.L.

2011-01-01

Background: In adults with Prader-Willi syndrome (PWS), limited information is available about pituitary function, more specifically the prevalence of growth hormone deficiency (GHD). The aim of this study was to gain more insight into endocrine function in PWS adults, with emphasis on GH secretion.

Growth and maturational changes in dense fibrous connective tissue following 14 days of rhGH supplementation in the dwarf rat

Science.gov (United States)

Kyparos, Antonios; Orth, Michael W.; Vailas, Arthur C.; Martinez, Daniel A.

2002-01-01

The purpose of this study was to investigate the impact of recombinant human growth hormone (rhGH) on patella tendon (PT), medial collateral ligament (MCL), and lateral collateral ligament (LCL) on collagen growth and maturational changes in dwarf GH-deficient rats. Twenty male Lewis mutant dwarf rats, 37 days of age, were randomly assigned to Dwarf + rhGH (n = 10) and Dwarf + vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt twice daily for 14 days. rhGH administration stimulated dense fibrous connective tissue growth, as demonstrated by significant increases in hydroxyproline specific activity and significant decreases in the non-reducible hydroxylysylpyridinoline (HP) collagen cross-link contents. The increase in the accumulation of newly accreted collagen was 114, 67, and 117% for PT, MCL, and LCL, respectively, in 72 h. These findings suggest that a short course rhGH treatment can affect the rate of new collagen production. However, the maturation of the tendon and ligament tissues decreased 18-25% during the rapid accumulation of de novo collagen. We conclude that acute rhGH administration in a dwarf rat can up-regulate new collagen accretion in dense fibrous connective tissues, while causing a reduction in collagen maturation. Copyright 2002 Elsevier Science Ltd.

Analysis of Surface Binding Sites (SBS) within GH62, GH13, and GH77

DEFF Research Database (Denmark)

Wilkens, Casper; Cockburn, Darrell; Andersen, Susan

2015-01-01

Certain interactions between carbohydrate active enzymes and polysaccharides involve surface binding sites (SBS) situated on catalytic domains outside of the active site. We recently undertook to develop a toolbox for SBS identification and characterization. In affinity gel electrophoresis (AGE...... of the reported SBSs. In GH13 SBSs have been seen in 17 subfamilies including SBSs with highly diverse functions in the same enzyme. Circumstantial evidence is provided for an SBS in the GH77 MalQ from Escherichia coli, the bacterial orthologue of Arabidopsis DPE2 involved in starch metabolism. Furthermore...

NREM sleep architecture and relation to GH/IGF-1 axis in Laron syndrome.

Science.gov (United States)

Verrillo, Elisabetta; Bizzarri, Carla; Cappa, Marco; Bruni, Oliviero; Pavone, Martino; Cutrera, Renato

2010-01-01

Laron syndrome (LS), known as growth hormone (GH) receptor deficiency, is a rare form of inherited GH resistance. Sleep disorders were described as a common feature of adult LS patients, while no data are available in children. Bi-directional interactions between human sleep and the somatotropic system were previously described, mainly between slow wave sleep and the nocturnal GH surge. To analyze the sleep macro- and microstructure in LS and to evaluate the influence of substitutive insulin-like growth factor 1 (IGF-1) therapy on it. Two young LS females underwent polysomnography; the first study was performed during IGF-1 therapy, the second one after a 3-month wash-out period. In both patients, the sleep macrostructure showed that time in bed, sleep period time, total sleep time, sleep efficiency and rapid eye movement (REM) percentage were all increased during wash-out. The sleep microstructure (cyclic alternating pattern: CAP) showed significantly higher EEG slow oscillations (A1%) in NREM sleep, both during IGF-1 therapy and wash-out. Sleep macrostructure in LS children is slightly affected by substitutive IGF-1 therapy. Sleep microstructure shows an increase of A1%, probably related to abnormally high hypothalamic GHRH secretion, due to GH insensitivity. Copyright 2010 S. Karger AG, Basel.

Isolated autosomal dominant growth hormone deficiency: an evolving pituitary deficit? A multicenter follow-up study.

Science.gov (United States)

Mullis, Primus E; Robinson, Iain C A F; Salemi, Souzan; Eblé, Andrée; Besson, Amélie; Vuissoz, Jean-Marc; Deladoey, Johnny; Simon, Dominique; Czernichow, Paul; Binder, Gerhard

2005-04-01

Four distinct familial types of isolated GH deficiency have been described so far, of which type II is the autosomal dominant inherited form. It is mainly caused by mutations within the first 6 bp of intervening sequence 3. However, other splice site and missense mutations have been reported. Based on in vitro experiments and transgenic animal data, there is strong evidence that there is a wide variability in phenotype in terms of the severity of GH deficiency. Therefore, we studied a total of 57 subjects belonging to 19 families suffering from different splice site as well as missense mutations within the GH-1 gene. The subjects presenting with a splice site mutation within the first 2 bp of intervening sequence 3 (5'IVS +1/+2 bp) leading to a skipping of exon 3 were found to be more likely to present in the follow-up with other pituitary hormone deficiencies. In addition, although the patients with missense mutations have previously been reported to be less affected, a number of patients presenting with the P89L missense GH form, showed some pituitary hormone impairment. The development of multiple hormonal deficiencies is not age dependent, and there is a clear variability in onset, severity, and progression, even within the same families. The message of clinical importance from these studies is that the pituitary endocrine status of all such patients should continue to be monitored closely over the years because further hormonal deficiencies may evolve with time.

GH and IGF-I levels are positively associated with musculotendinous collagen expression: Experiments in acromegalic and GHD patients

DEFF Research Database (Denmark)

Doessing, Simon; Holm, Lars; Heinemeier, Katja

2010-01-01

OBJECTIVE: Disproportionate growth of musculoskeletal tissue is a major cause of morbidity in both acromegalic (ACRO) and GH-deficient (GHD) patients. GH/IGF1 is likely to play an important role in the regulation of tendon and muscle collagen. We hypothesized that the local production of collagen...... is associated with the level of GH/IGF1.DESIGN AND METHODS: As primary outcomes, collagen mRNA expression and collagen protein fractional synthesis rate (FSR) were determined locally in skeletal muscle and tendon in nine ACRO and nine GHD patients. Moreover, muscle myofibrillar protein synthesis and tendon...... collagen morphology were determined.RESULTS AND CONCLUSIONS: Muscle collagen I and III mRNA expression was higher in ACRO patients versus GHD patients (PIGF1Ea and IGF1Ec...

Growth Hormone (GH) and Cardiovascular System

Science.gov (United States)

Díaz, Oscar; Devesa, Pablo

2018-01-01

This review describes the positive effects of growth hormone (GH) on the cardiovascular system. We analyze why the vascular endothelium is a real internal secretion gland, whose inflammation is the first step for developing atherosclerosis, as well as the mechanisms by which GH acts on vessels improving oxidative stress imbalance and endothelial dysfunction. We also report how GH acts on coronary arterial disease and heart failure, and on peripheral arterial disease, inducing a neovascularization process that finally increases flow in ischemic tissues. We include some preliminary data from a trial in which GH or placebo is given to elderly people suffering from critical limb ischemia, showing some of the benefits of the hormone on plasma markers of inflammation, and the safety of GH administration during short periods of time, even in diabetic patients. We also analyze how Klotho is strongly related to GH, inducing, after being released from the damaged vascular endothelium, the pituitary secretion of GH, most likely to repair the injury in the ischemic tissues. We also show how GH can help during wound healing by increasing the blood flow and some neurotrophic and growth factors. In summary, we postulate that short-term GH administration could be useful to treat cardiovascular diseases. PMID:29346331

Effects of growth hormone therapy on thyroid function of growth hormone-deficient adults with and without concomitant thyroxine-substituted central hypothyroidism

DEFF Research Database (Denmark)

Jørgensen, J O; Pedersen, S A; Laurberg, P

1989-01-01

Administration of human GH to GH-deficient patients has yielded conflicting results concerning its impact on thyroid function, ranging from increased resting metabolic rate to induction of hypothyroidism. However, most studies have been casuistic or uncontrolled and have used pituitary-derived GH...

Bone Mineral Density and Body Composition in Adolescents with Childhood-Onset Growth Hormone Deficiency

NARCIS (Netherlands)

Boot, Annemieke M.; van der Sluis, Inge M.; Krenning, Eric P.; Keizer-Schrama, Sabine M. P. F. de Muinck

2009-01-01

Background/Aims: The aim of the present study was to evaluate bone mineral density (BMD) and body composition of patients with childhood-onset growth hormone (GH) deficiency (GHD) treated with GH during the transition period. Methods: BMD and body composition, measured by dual-energy X-ray

Same Phenotype in Children with Growth Hormone Deficiency and Resistance

Science.gov (United States)

Ioimo, Irene; Guarracino, Carmen; Meazza, Cristina; Domené, Horacio M.

2018-01-01

By definition, about 2.5% of children show a short stature due to several causes. Two clinical conditions are characterized by serum IGF-I low levels, idiopathic GH deficiency (IGHD), and GH insensitivity (GHI), and the phenotypic appearance of these patients may be very similar. We studied two children with short stature and similar phenotypes. The first case showed frontal bossing, doll face, acromicria, and truncal obesity, with a GH peak Laron syndrome was confirmed after the molecular analysis of the GH receptor (GHR) gene. IGHD type IA and Laron syndrome is characterized by opposite circulating levels of GH, while both have reduced levels of IGF-I, with an overlapping clinical phenotype, lacking the effects of IGF-I on cartilage. These classical cases show the importance of differential diagnosis in children with severe short stature. PMID:29850346

Hypophysectomy eliminates and growth hormone (GH) maintains the midpregnancy elevation in GH receptor and serum binding protein in the mouse

International Nuclear Information System (INIS)

Sanchez-Jimenez, F.; Fielder, P.J.; Martinez, R.R.; Smith, W.C.; Talamantes, F.

1990-01-01

[ 125 I]Iodomouse GH [( 125 I]iodo-mGH) binding to samples of serum and hepatic microsomal membranes was measured in hypophysectomized pregnant, sham-operated pregnant, intact pregnant, and intact adult virgin mice. Surgeries were carried out on day 11 of pregnancy, and the animals were killed on day 14. The binding of mGH to both serum and hepatic microsomal membranes of intact virgin mice was much lower than to those of intact pregnant mice. In hypophysectomized mice, the mGH-binding capacity of both serum and hepatic microsomes decreased to values similar to those of nonpregnant mice. No significant differences were observed between intact and sham-operated pregnant animals in the maternal serum mGH concentration, the serum GH-binding protein concentration, or the hepatic GH receptor concentration. GH receptor and binding protein-encoding mRNAs were also higher in intact and sham-operated pregnant mice than in virgin and hypophysectomized mice. Hypophysectomized mice were treated with 200 micrograms/day bovine GH, administered by osmotic minipump; after 3 days of treatment, a significant elevation of hepatic GH receptor and serum GH-binding protein levels was observed. These results demonstrate an up-regulation of hepatic GH receptors and serum GH-binding protein by GH during pregnancy in the mouse

Growth hormone treatment during pregnancy in a growth hormone-deficient woman

DEFF Research Database (Denmark)

Müller, J; Starup, J; Christiansen, J S

1995-01-01

protein 3 (IGFBP-3) during pregnancy, as well as birth weight and hormone levels after delivery in a 25-year-old woman with idiopathic, isolated GH deficiency diagnosed at the age of 7 years. As part of a clinical trial, the patient was treated with 2 IU/M2 GH for a period of 5 years. At this time she...

Defective membrane expression of human growth hormone (GH) receptor causes Laron-type GH insensitivity syndrome.

Science.gov (United States)

Duquesnoy, P; Sobrier, M L; Amselem, S; Goossens, M

1991-01-01

Mutations in the growth hormone receptor (GHR) gene can cause growth hormone (GH) resistance. Given the sequence homology between the extracellular domain of the GHR and a soluble GH-binding protein (GH-BP), it is remarkable that GH-BP binding activity is absent from the serum of patients with Laron-type GH insensitivity, a hereditary form of severe dwarfism. We have previously identified a mutation within the extracellular domain of this receptor, replacing phenylalanine by serine at position 96 of the mature protein, in a patient with Laron syndrome. We have now investigated the effect of this Phe----Ser substitution on hormone binding activity by expressing the total human GHR cDNA and mutant form in eukaryotic cells. The wild-type protein expressed was able to bind GH but no plasma membrane binding was detectable on cells transfected with the mutant cDNA; this was also the case of cells transfected with a Phe96----Ala mutant cDNA, suggesting that the lack of binding activity is not due to a posttranslational modification of serine. Examination of the variant proteins in subcellular fractions revealed the presence of specific GH binding activity in the lysosomal fraction, whereas immunofluorescence studies located mutant proteins in the cytosol. Our findings suggest that these mutant GHRs fail to follow the correct intracellular transport pathway and underline the potential importance of this phenylalanine residue, which is conserved among the GH, prolactin, and erythropoietin receptors that belong to the same cytokine receptor superfamily. Images PMID:1719554

Pioglitazone treatment increases spontaneous growth hormone (GH) secretion and stimulated GH levels in polycystic ovary syndrome

DEFF Research Database (Denmark)

Glintborg, Dorte; Støving, René Klinkby; Hagen, Claus

2005-01-01

BACKGROUND: Low GH levels, probably due to insulin resistance and increased abdominal fat mass, are well described in polycystic ovary syndrome (PCOS). GH acts as an important ovarian cogonadotropin, and GH disturbances may be an additional pathogenic factor in PCOS. Decreased abdominal fat mass...

Effects of methimazole treatment on growth hormone (GH) response to GH-releasing hormone in patients with hyperthyroidism.

Science.gov (United States)

Giustina, A; Ferrari, C; Bodini, C; Buffoli, M G; Legati, F; Schettino, M; Zuccato, F; Wehrenberg, W B

1990-12-01

In vitro studies have demonstrated that thyroid hormones can enhance basal and stimulated growth hormone secretion by cultured pituitary cells. However, both in man and in the rat the effects of high thyroid hormone levels on GH secretion are unclear. The aim of our study was to test the GH response to human GHRH in hyperthyroid patients and to evaluate the effects on GH secretion of short- and long-term pharmacological decrease of circulating thyroid hormones. We examined 10 hyperthyroid patients with recent diagnosis of Graves' disease. Twelve healthy volunteers served as controls. All subjects received a bolus iv injection of GHRH(1-29)NH2, 100 micrograms. Hyperthyroid patients underwent a GHRH test one and three months after starting antithyroid therapy with methimazole, 10 mg/day po. GH levels at 15, 30, 45, 60 min and GH peak after stimulus were significantly lower in hyperthyroid patients than in normal subjects. The GH peak was also delayed in hyperthyroid patients. After one month of methimazole therapy, most of the hyperthyroid patients had thyroid hormone levels in the normal range, but they did not show significant changes in GH levels after GHRH, and the GH peak was again delayed. After three months of therapy with methimazole, the hyperthyroid patients did not show a further significant decrease in serum thyroid hormone levels. However, mean GH levels from 15 to 60 min were significantly increased compared with the control study. The GH peak after GHRH was also earlier than in the pre-treatment study.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome

Directory of Open Access Journals (Sweden)

Sang Soo Lee

2017-03-01

Full Text Available Growth hormone (GH is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD caused by pituitary stalk interruption syndrome (PSIS. The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patient's blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD. Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD.

Insulin and GH signaling in human skeletal muscle in vivo following exogenous GH exposure: impact of an oral glucose load.

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Thomas Krusenstjerna-Hafstrøm

2011-05-01

Full Text Available GH induces acute insulin resistance in skeletal muscle in vivo, which in rodent models has been attributed to crosstalk between GH and insulin signaling pathways. Our objective was to characterize time course changes in signaling pathways for GH and insulin in human skeletal muscle in vivo following GH exposure in the presence and absence of an oral glucose load.Eight young men were studied in a single-blinded randomized crossover design on 3 occasions: 1 after an intravenous GH bolus 2 after an intravenous GH bolus plus an oral glucose load (OGTT, and 3 after intravenous saline plus OGTT. Muscle biopsies were taken at t = 0, 30, 60, and 120. Blood was sampled at frequent intervals for assessment of GH, insulin, glucose, and free fatty acids (FFA.GH increased AUC(glucose after an OGTT (p<0.05 without significant changes in serum insulin levels. GH induced phosphorylation of STAT5 independently of the OGTT. Conversely, the OGTT induced acute phosphorylation of the insulin signaling proteins Akt (ser(473 and thr(308, and AS160.The combination of OGTT and GH suppressed Akt activation, whereas the downstream expression of AS160 was amplified by GH. WE CONCLUDED THE FOLLOWING: 1 A physiological GH bolus activates STAT5 signaling pathways in skeletal muscle irrespective of ambient glucose and insulin levels 2 Insulin resistance induced by GH occurs without a distinct suppression of insulin signaling proteins 3 The accentuation of the glucose-stimulated activation of AS 160 by GH does however indicate a potential crosstalk between insulin and GH.ClinicalTrials.gov NCT00477997.

GH Responsiveness to Combined GH-Releasing Hormone and Arginine Administration in Obese Patients with Fibromyalgia Syndrome

Directory of Open Access Journals (Sweden)

Antonello E. Rigamonti

2017-01-01

Full Text Available Reportedly, fibromyalgia (FM is frequently associated with reduced IGF-1 levels and GH hyporesponsiveness to different GH stimulation tests. Since there is a high prevalence of obesity in FM, and obesity itself is characterized by hyposomatotropism, the aim of this study was to assess IGF-1 levels and GH responsiveness in sixteen severely obese women suffering from FM, who, subdivided into two subgroups on the basis of their age-dependent IGF-1 values (> or <−2 SDS, underwent the combined GHRH plus arginine test. Four out of 16 obese women with FM (25% had low IGF-1 SDS values, 2 cases of this subgroup (12.5% failing also to normally respond to the test. Among patients with normal GH responses, 4 showed a delayed GH peak. The subgroup with low IGF-1 SDS values had higher BMI than that with normal IGF-1 SDS. GH peak and area under the curve were not correlated with CRP, ESR, or tender point score, while significant correlations were found with fat-free mass and fat mass. In conclusion, this study shows the existence of a high prevalence of GH-IGF-1 dysfunction in patients with both FM and obesity, presumably as a consequence of the obese rather than fibromyalgic condition.

GH receptor signaling in skeletal muscle and adipose tissue in human subjects following exposure to an intravenous GH bolus

DEFF Research Database (Denmark)

Jørgensen, Jens O L; Jessen, Niels; Pedersen, Steen Bønløkke

2006-01-01

Growth hormone (GH) regulates muscle and fat metabolism, which impacts on body composition and insulin sensitivity, but the underlying GH signaling pathways have not been studied in vivo in humans. We investigated GH signaling in biopsies from muscle and abdominal fat obtained 30 (n = 3) or 60 (n...... was measured by in vitro phosphorylation of PI. STAT5 DNA binding activity was assessed with EMSA, and the expression of IGF-I and SOCS mRNA was measured by real-time RT-PCR. GH induced a 52% increase in circulating FFA levels with peak values after 155 min (P = 0.03). Tyrosine-phosphorylated STAT5...... tended to increase after GH in muscle and fat, respectively. We conclude that 1) STAT5 is acutely activated in human muscle and fat after a GH bolus, but additional downstream GH signaling was significant only in fat; 2) the direct GH effects in muscle need further characterization; and 3) this human...

Culture, Environment, and Food to Prevent Vitamin A Deficiency ...

International Development Research Centre (IDRC) Digital Library (Canada)

Culture, Environment, and Food to Prevent Vitamin A Deficiency. Book cover Culture, Environment, and Food to Prevent Vitamin A Deficiency. Auteur(s) : H.V. Kuhnlein and G.H. Pelto. Maison(s) d'édition : INFDC, IDRC. 1 janvier 1997. ISBN : Out of print. 220 pages. e-ISBN : 1552504409. Téléchargez le PDF · Téléchargez ...

GH replacement in hypopituitarism improves lipid profile and quality of life independently of changes in obesity variables

DEFF Research Database (Denmark)

Abrams, P.; Boquete, H.; Fideleff, H.

2008-01-01

OBJECTIVE: GH deficiency (GHD) in adults is characterized by elevated body mass index (BMI), increased waist girth (WG) and increased fat mass (FM). Information about how these indicators of obesity affect the lipid profile and quality of life (QoL) of GHD subjects is scarce. It is also unclear h...

Manipulation of the Growth Hormone-Insulin-Like Growth Factor (GH-IGF) Axis: A Treatment Strategy to Reverse the Effects of Early Life Developmental Programming.

Science.gov (United States)

Reynolds, Clare M; Perry, Jo K; Vickers, Mark H

2017-08-08

Evidence from human clinical, epidemiological, and experimental animal models has clearly highlighted a link between the early life environment and an increased risk for a range of cardiometabolic disorders in later life. In particular, altered maternal nutrition, including both undernutrition and overnutrition, spanning exposure windows that cover the period from preconception through to early infancy, clearly highlight an increased risk for a range of disorders in offspring in later life. This process, preferentially termed "developmental programming" as part of the developmental origins of health and disease (DOHaD) framework, leads to phenotypic outcomes in offspring that closely resemble those of individuals with untreated growth hormone (GH) deficiency, including increased adiposity and cardiovascular disorders. As such, the use of GH as a potential intervention strategy to mitigate the effects of developmental malprogramming has received some attention in the DOHaD field. In particular, experimental animal models have shown that early GH treatment in the setting of poor maternal nutrition can partially rescue the programmed phenotype, albeit in a sex-specific manner. Although the mechanisms remain poorly defined, they include changes to endothelial function, an altered inflammasome, changes in adipogenesis and cardiovascular function, neuroendocrine effects, and changes in the epigenetic regulation of gene expression. Similarly, GH treatment to adult offspring, where an adverse metabolic phenotype is already manifest, has shown efficacy in reversing some of the metabolic disorders arising from a poor early life environment. Components of the GH-insulin-like growth factor (IGF)-IGF binding protein (GH-IGF-IGFBP) system, including insulin-like growth factor 1 (IGF-1), have also shown promise in ameliorating programmed metabolic disorders, potentially acting via epigenetic processes including changes in miRNA profiles and altered DNA methylation. However, as

Ghrelin- and GH-induced insulin resistance

DEFF Research Database (Denmark)

Vestergaard, Esben Thyssen; Krag, Morten B; Poulsen, Morten M

2013-01-01

Supraphysiological levels of ghrelin and GH induce insulin resistance. Serum levels of retinol-binding protein-4 (RBP4) correlate inversely with insulin sensitivity in patients with type 2 diabetes. We aimed to determine whether ghrelin and GH affect RBP4 levels in human subjects.......Supraphysiological levels of ghrelin and GH induce insulin resistance. Serum levels of retinol-binding protein-4 (RBP4) correlate inversely with insulin sensitivity in patients with type 2 diabetes. We aimed to determine whether ghrelin and GH affect RBP4 levels in human subjects....

[Issues related to secondary osteoporosis associated with growth hormone deficiency in adulthood].

Science.gov (United States)

Kužma, Martin; Jackuliak, Peter; Killinger, Zdenko; Vaňuga, Peter; Payer, Juraj

Growth hormone (GH) increases linear bone growth through complex hormonal reactions, mainly mediated by insulin like growth factor 1 (IGF1) that is produced mostly by hepatocytes under influence of GH and stimulates differentiation of epiphyseal prechondrocytes. IGF1 and GH play a key role in the linear bone growth after birth and regulation of bone remodelation during the entire lifespan. It is known that adult GH deficient (GHD) patients have decreased BMD and increased risk of low-impact fractures. Most data gathered thus far on the effect of GH replacement on bone status comprise the measurement of quantitative changes of bone mass. Some animal studies with GHD showed that the bone microarchitecture, measured using computed tomography methods, is significantly compromised and improve after GH replacement. However, human studies did not show significantly decreased bone microarchitecture, but limited methodological quality does not allow firm conclusions on this subject.Key words: bone mass - bone quality - fracture - growth hormone - IGF1.

GH response to GHRH combined with pyridostigmine or arginine in different conditions of low somatotrope secretion in adulthood: obesity and Cushing's syndrome in comparison with hypopituitarism.

Science.gov (United States)

Procopio, M; Maccario, M; Savio, P; Valetto, M R; Aimaretti, G; Grottoli, S; Oleandri, S E; Baffoni, C; Tassone, F; Arvat, E; Camanni, F; Ghigo, E

1999-01-01

Diagnosing GH deficiency in adults is difficult due to the age-related variations of GH/IGF-I axis and the influence of nutrition. Nowadays, GH replacement is allowed for patients with GH peak to provocative stimuli nutrition status. We aimed to verify the GH response to GHRH (1 mg/kg i.v.) combined with pyridostigmine (PD, 120 mg p.o.) or arginine (ARG, 0.5 g/kg i.v.), in 26 hypopituitaric patients (GHD), in 11 obese women (OB), in 8 women with Cushing's syndrome (CS), and in 72 control subjects (NS). IGF-I levels in GHD were lower than those in OB (p < 0.01) and in CS (p < 0.01) which, in turn, were lower to those in NS (p < 0.02). In NS, the GH peak responses to GHRH + PD and GHRH + ARG were similar and the minimum normal GH peak was 16.5 mg/L. GHD had GH responses similar, lower than those in NS (p < 0.01) and always below the normal limit. However, only 12/20 and 8/14 had peaks < 3 micrograms/L; conventionally, below this limit severe GH deficiency is shown and rhGH replacement is allowed. In OB, the GH responses to GHRH + PD and GHRH + ARG were similar, lower (p < 0.01) and higher (p < 0.01) than those in NS and GHD, respectively. Six out of 11 OB had GH peaks below the normal limits but nobody < 3 micrograms/L. In CS, the GH response to GHRH + PD was lower than that to GHRH + ARG (p < 0.01); both these responses were lower than those in NS (p < 0.01) and even in OB (p < 0.01) but higher than those in GHD (p < 0.01). All and 7/8 CS had GH peaks lower than normal limits after PD + GHRH and ARG + GHRH, respectively while 6/8 showed GH peak < 3 micrograms/L after PD + GHRH but only 1 after ARG + GHRH. Present data demonstrate that the maximal somatotrope secretory capacity is reduced in OB and even more in CS. From a diagnostic point of view, PD + GHRH and ARG + GHRH tests distinguish OB from severe GHD. As hypercortisolism impairs the activity of cholinesterase inhibitors, only ARG + GHRH, but not PD + GHRH is a reliable test to explore the maximal somatotrope

GH Responsiveness to Combined GH-Releasing Hormone and Arginine Administration in Obese Patients with Fibromyalgia Syndrome.

Science.gov (United States)

Rigamonti, Antonello E; Grugni, Graziano; Arreghini, Marco; Capodaglio, Paolo; De Col, Alessandra; Agosti, Fiorenza; Sartorio, Alessandro

2017-01-01

Reportedly, fibromyalgia (FM) is frequently associated with reduced IGF-1 levels and GH hyporesponsiveness to different GH stimulation tests. Since there is a high prevalence of obesity in FM, and obesity itself is characterized by hyposomatotropism, the aim of this study was to assess IGF-1 levels and GH responsiveness in sixteen severely obese women suffering from FM, who, subdivided into two subgroups on the basis of their age-dependent IGF-1 values (> or BMI than that with normal IGF-1 SDS. GH peak and area under the curve were not correlated with CRP, ESR, or tender point score, while significant correlations were found with fat-free mass and fat mass. In conclusion, this study shows the existence of a high prevalence of GH-IGF-1 dysfunction in patients with both FM and obesity, presumably as a consequence of the obese rather than fibromyalgic condition.

The basic route of the nuclear translocation porcine growth hormone (GH)-growth hormone receptor (GHR) complex (pGH/GHR) in porcine hepatocytes.

Science.gov (United States)

Hainan, Lan; Huilin, Liu; Khan, Mahamad; Xin, Zheng; YuJiang, Yang; Hui, Zhang; Naiquan, Yao

2018-06-08

Traditional views suggest that growth hormone and the growth hormone receptor (GH/GHR complex) exert their functions only on the plasma membrane. This paradigm, however, has been challenged by recent new findings that the GH/GHR complex could translocate into cell nuclei where they could still exhibit important physiological functions. We also reported the nuclear localization of porcine GH/GHR and their potential functions in porcine hepatocytes. However, the basic path of pGH/GHR's nuclear translocation remains unclear. Combining previous research results and our current findings, we proposed two basic routes of pGH/GHR's nuclear transportation as follows: 1) after pGH binding to GHR, pGH/GHR enters into the cytoplasm though clathrin- or caveolin-mediated endocytosis, then the pGH/GHR complex enters into early endosomes (Rab5-positive), and the endosome carries the GH/GHR complex to the endoplasmic reticulum (ER). After endosome docking on the ER, the endosome starts fission, and the pGH/GHR complex enters into the ER lumen. Then the pGH/GHR complex transports into the cytoplasm, possibly by the ERAD pathway. Subsequently, the pGH/GHR complex interacts with IMPα/β, which, in turn, mediates GH/GHR nuclear localization; 2) pGH binds with the GHR on the cell membrane and, subsequently, pGH/GHR internalizes into the cell and enters into the endosome (this endosome may belong to a class of endosomes called envelope-associated endosomes (NAE)). Then, the endosome carries the pGH/GHR to the nuclear membrane. After docking on the nuclear membrane, the pGH/GHR complex fuses with the nuclear membrane and then enters into the cell nucleus. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of a 7-day continuous infusion of octreotide on circulating levels of growth factors and binding proteins in growth hormone (GH)-treated GH-deficient patients

DEFF Research Database (Denmark)

Laursen, Torben; Møller, Jens; Fisker, Sanne

1999-01-01

Abstract In patients with acromegaly, clinical improvement has been reported after octreotide (OCT) treatment, even in cases of only a moderate suppression of growth hormone (GH) levels. In rats, OCT suppresses IGF-I mRNA expression and generation of serum and tissue IGF-I levels. A direct effect...

Head circumference in untreated and IGF-I treated patients with Laron syndrome: comparison with untreated and hGH-treated children with isolated growth hormone deficiency.

Science.gov (United States)

Laron, Zvi; Iluz, Moshe; Kauli, Rivka

2012-04-01

Head circumference (HC) is a simple and practical measure of brain size, development and longitudinal measurements of the HC in childhood are an index of brain growth. To determine the effects of long IGF-I deficiency and treatment on HC in patients with Laron syndrome (LS). 20 untreated adult LS patients, aged 48.4±11.2 years and 13 LS patients treated between ages of 5.6±4 to 11.3±3 years were studied. 15 patients with congenital IGHD treated between age 6.1±4 and 13±4 by hGH served as controls. HC was expressed as standard deviation (SD) and Ht as SDS. HC was measured and plotted on Nellhaus charts. Linear height (Ht) was measured by a Harpenden Stadiometer. The mean HC deficit of the adult untreated LS males was -2.9±0.6 SD compared to a Ht deficit of -7.0±1.7 SDS. The HC of the LS adult females was -3.6±1 SD compared to a Ht SDS of -6.9±1.5 (pdeficit decreased only by 1.5 SDS. hGH treatment of cIGHD children increased the HC from -2.0±1.8 to 0.3±1.2 SD and the Ht SDS from -4.8±1.6 to 1.6±1.0. Copyright © 2012 Elsevier Ltd. All rights reserved.

Prevalence of Growth Hormone Deficiency in Hashimoto's Thyroiditis

NARCIS (Netherlands)

Eskes, Silvia A.; Endert, Erik; Fliers, Eric; Wiersinga, Wilmar M.

2010-01-01

Context: Autoimmune hypophysitis can result in GH deficiency (GHD) and is associated with other autoimmune endocrine diseases like Hashimoto's thyroiditis. Recent studies suggest a high prevalence (5%) of GHD in Hashimoto's thyroiditis. Objective: Our objective was to establish the prevalence of GHD

Growth hormone (GH) activity is associated with increased serum oestradiol and reduced Anti-Müllerian Hormone in healthy male volunteers treated with GH and a GH antagonist

DEFF Research Database (Denmark)

Andreassen, M; Frystyk, Jan; Faber, J

2013-01-01

Growth hormone (GH) and insulin-like growth factor I (IGF-I) receptors are present on pituitary gonadotrophs and on testicular Leydig and Sertoli cells. Thus, the GH/IGF-I system may modulate the pituitary-gonadal axis in males. This is a randomized cross-over study. Eight healthy male volunteers...... (160-290) vs. 106 (97-157) μg/L, p = 0.001) and oestradiol (86 ± 28 vs. 79 ± 25 pm, p = 0.060) decreased. No significant changes or trends in the other reproductive hormones occurred during the two treatment regimens. GH/IGF-I activity was positively associated with serum oestradiol, suggesting that GH...

Pharmacokinetics and metabolic effects of growth hormone injected subcutaneously in growth hormone deficient patients: thich versus abdomen

DEFF Research Database (Denmark)

Laursen, Torben; Jørgensen, Jens Otto Lunde; Christiansen, Jens Sandahl

1994-01-01

and IGFBP-3), glucose, insulin, non-esterified fatty acids (NEFA), glycerol, 3-hydroxybutyrate, alanine, lactate and glucagon were measured for 37 hours after GH injection (3 IU/m2 at 1900 hour). PATIENTS: Nine GH deficient patients (five males, four females). RESULTS: The mean (+/- SEM) thickness of the s...

Type I and III procollagen propeptides in growth hormone-deficient patients

DEFF Research Database (Denmark)

Jensen, L T; Jørgensen, J O; Risteli, J

1991-01-01

The effect of increasing doses of growth hormone on collagen synthesis in GH-treated GH-deficient patients was determined in a short-term study. The synthesis of type I and III collagen was estimated by measurements of the carboxyterminal propeptide of type I procollagen and the aminoterminal...... propeptide of type III procollagen. Type I collagen is mainly found in bone and type III collagen in loose connective tissue. We observed a GH dose dependency of both procollagen propeptides. Serum type I procollagen propeptide was significantly higher following GH doses of 4 and 6 IU/day for 14 days...... procollagen propeptide increased twice as much as type I procollagen propeptide, by 47 vs 25%, at a GH dose of 6 IU/day compared with 2 IU/day. The differences between the effects on type I and type III collagen may reflect differences in secretion or turn-over rate of collagen in bone and loose connective...

Same Phenotype in Children with Growth Hormone Deficiency and Resistance

Directory of Open Access Journals (Sweden)

Irene Ioimo

2018-01-01

Full Text Available By definition, about 2.5% of children show a short stature due to several causes. Two clinical conditions are characterized by serum IGF-I low levels, idiopathic GH deficiency (IGHD, and GH insensitivity (GHI, and the phenotypic appearance of these patients may be very similar. We studied two children with short stature and similar phenotypes. The first case showed frontal bossing, doll face, acromicria, and truncal obesity, with a GH peak <0.05 ng/ml after stimuli and undetectable serum IGF-I levels. After PCR amplification of the whole GH1 gene, type IA idiopathic GHD was diagnosed. The second case had cranium hypoplasia, a large head, protruding forehead, saddle nose, underdeveloped mandible, and a micropenis. Basal GH levels were high (28.4 ng/ml while serum IGF-I levels were low and unchangeable during the IGF-I generation test. Laron syndrome was confirmed after the molecular analysis of the GH receptor (GHR gene. IGHD type IA and Laron syndrome is characterized by opposite circulating levels of GH, while both have reduced levels of IGF-I, with an overlapping clinical phenotype, lacking the effects of IGF-I on cartilage. These classical cases show the importance of differential diagnosis in children with severe short stature.

The impact of idiopathic childhood-onset growth hormone deficiency (GHD) on bone mass in subjects without adult GHD

DEFF Research Database (Denmark)

Lange, Martin; Müller, Jørn; Svendsen, Ole Lander

2005-01-01

Despite seemingly adequate growth hormone (GH) treatment during childhood, children with GH deficiency (GHD) have reduced bone mineral density (BMD) at final height. The aim was to evaluate BMD and bone mineral content (BMC) in adults treated for idiopathic childhood-onset (CO) GHD, 18 years after...

Skin morphological changes in growth hormone deficiency and acromegaly

DEFF Research Database (Denmark)

Lange, Merete Wolder; Thulesen, J; Feldt-Rasmussen, U

2001-01-01

To evaluate the histomorphology of skin and its appendages, especially eccrine sweat glands, in patients with GH disorders, because reduced sweating ability in patients with growth hormone deficiency (GHD) is associated with increased risk of hyperthermia under stressed conditions....

Correlation between GH and IGF-1 during treatment for acromegaly.

Science.gov (United States)

Oldfield, Edward H; Jane, John A; Thorner, Michael O; Pledger, Carrie L; Sheehan, Jason P; Vance, Mary Lee

2017-06-01

OBJECTIVE The relationship between growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in patients with acromegaly as serial levels drop over time after treatment has not been examined previously. Knowledge of this relationship is important to correlate pretreatment levels that best predict response to treatment. To examine the correlation between GH and IGF-1 and IGF-1 z-scores over a wide range of GH levels, the authors examined serial GH and IGF-1 levels at intervals before and after surgery and radiosurgery for acromegaly. METHODS This retrospective analysis correlates 414 pairs of GH and IGF-1 values in 93 patients with acromegaly. RESULTS Absolute IGF-1 levels increase linearly with GH levels only up to a GH of 4 ng/ml, and with IGF-1 z-scores only to a GH level of 1 ng/ml. Between GH levels of 1 and 10 ng/ml, increases in IGF-1 z-scores relative to changes in GH diminish and then plateau at GH concentrations of about 10 ng/ml. From patient to patient there is a wide range of threshold GH levels beyond which IGF-1 increases are no longer linear, GH levels at which the IGF-1 response plateaus, IGF-1 levels at similar GH values after the IGF-1 response plateaus, and of IGF-1 levels at similar GH levels. CONCLUSIONS In acromegaly, although IGF-1 levels represent a combination of the integrated effects of GH secretion and GH action, the tumor produces GH, not IGF-1. Nonlinearity between GH and IGF-1 occurs at GH levels far below those previously recognized. To monitor tumor activity and tumor viability requires measurement of GH levels.

Reduction of free fatty acids by acipimox enhances the growth hormone (GH) responses to GH-releasing peptide 2 in elderly men

NARCIS (Netherlands)

Smid, HEC; de Vries, WR; Niesink, M; Bolscher, E; Waasdorp, EJ; Dieguez, C; Casanueva, FF; Koppeschaar, HPF

2000-01-01

GH release is increased by reducing circulating free fatty acids (FFAs). Aging is associated with decreased plasma GH concentrations. We evaluated GH releasing capacity in nine healthy elderly men after administration of GH-releasing peptide 2 (GHRP-2), with or without pretreatment with the

Characterization of pituitary function with emphasis on GH secretion in the chronic fatigue syndrome.

Science.gov (United States)

Moorkens, G; Berwaerts, J; Wynants, H; Abs, R

2000-07-01

TSH levels (1.6 +/- 1.0 mU/l vs. 1.0 +/- 0.4 mU/l; P = 0.011) were found in CFS patients. Serum free thyroxine was comparable in both groups. Visceral fat mass was significantly higher in CFS patients (86.6 +/- 34.9 cm2 vs. 51.5 +/- 15.7 cm2; P < 0.001). We observed a significant impairment of GH response during insulin-induced hypoglycaemia and a low nocturnal GH secretion in CFS patients. These changes did, however, not lead to different concentrations in serum IGF-I. The clinical expression of this inadequate GH secretion can thus be questioned, although the alteration in body composition may be related to this relative GH deficiency. Significantly increased prolactin and TSH levels were found when compared to controls. These findings give support to the hypothesis of a decreased dopaminergic tone in CFS. Further investigations are required in order to identify specific adaptations within the neurotransmitter system in CFS and to determine the clinical importance of the impaired GH homeostasis.

Plerocercoid growth factor (PGF), a human growth hormone (hGH) analogue produced by the tapeworm Spirometra mansonoides, has direct insulin-like action in adipose tissue of normal rats in vitro

International Nuclear Information System (INIS)

Salem, M.A.M.; Phares, C.K.

1986-01-01

The metabolic actions of GH can be divided into acute (insulin-like) and chronic (lipolytic/anti-insulin). The insulin-like actions of GH are most readily elicited in GH-deficient animals as GH induces resistance to its own insulin-like action. Like GH, PGF stimulates growth and cross-reacts with anti-hGH antibodies. Independent experiments were conducted comparing the direct actions of PGF to insulin or hGH in vitro. Insulin-like effects were determined by the ability of PGF, insulin or hGH to stimulate [U- 14 C]glucose metabolism in epidydimal fat pads from normal rats and by inhibition of epinephrine-stimulated lipolysis. Direct stimulation of lipolysis was used as anti-insulin activity. To determine if PGF competes for insulin or GH receptors, adipocytes (3 x 10 5 cells/ml) were incubated with either [ 125 I]insulin or [ 125 I]hGH +/- PGF, +/- insulin or +/- hGH. PGF stimulated glucose oxidation and 14 C-incorporation into lipids. Insulin, hGH and PGF inhibited lipolysis (33%, 29% and 34%, respectively). Adipose tissue was very sensitive to the lipolytic effect of hGH but PGF was neither lipolytic nor did it confer refractoriness to its insulin-like action. PGF bound to GH but not to insulin receptors. Therefore, PGF had direct insulin-like effects but did not stimulate lipolysis in tissue from normal rats in vitro

Multiple endocrinopathies (growth hormone deficiency, autoimmune hypothyroidism and diabetes mellitus in Kearns-Sayre syndrome

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A. Berio

2013-06-01

Full Text Available Kearns-Sayre syndrome is characterized by onset before 20 years, chronic progressive external opthalmoplegia, pigmentary retinal degeneration, and ataxia (and/or hearth block, and/or high protein content in the cerebrospinal fluid in the presence of mtDNA rearrangements. Multiple endocrine dysfunction associated with this syndrome was rarely reported. In this paper, the Authors report on a female patient with Kearns-Sayre syndrome with large heteroplasmic mtDNA deletion, absence of cytochrome c oxidase in many muscle fibers, partial GH deficiency, hypothyroidism and subsequently insulin dependent diabetes mellitus (IDDM. Anti-thyroid peroxidase and antithyreoglobulin antibodies were present in high titer in serum while anti-islet cell antibodies were absent. The patient developed thyroiditis with Hashimoto encephalopathy. The presence of GH deficiency, autoimmune thyroiditis with hypothyroidism and IDDM distinguishes this case from others and confirms the association of Kearns-Sayre syndrome with multiple endocrine dysfunction. Hashimoto encephalopathy and anti-thyroideal antibodies suggest that in this patient, predisposed by a genetic factor (a mitochondrial deletion anti-thyroideal antibodies may have contributed to the hypothyroidism and, by interfering with cerebral mitochondrial function, may have caused the encephalopathy. GH deficiency and IDDM can be attributed to oxidative phosphorylation deficiency but the autoimmunity may also have played a role in the production of glandular insufficiencies. It seems important to search for endocrine autoimmunity in every case of KSS.

Lack of regulation of 11β-hydroxysteroid dehydrogenase type 1 during short-term manipulation of GH in patients with hypopituitarism

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Sigurjonsdottir, Helga A; Andrew, Ruth; Stimson, Roland H; Johannsson, Gudmundur; Walker, Brian R

2009-01-01

Objective Evidence from long-term clinical studies measuring urinary steroid ratios, and from in vitro studies, suggests that GH administered for longer than 2 months down-regulates 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), thereby reducing cortisol regeneration in liver and adipose tissue. We aimed to measure acute effects of GH on 11β-HSD1 in liver and adipose tissue in vivo, including using a stable isotope tracer. Design Observational studies of GH withdrawal and reintroduction in patients with hypopituitarism. Methods Twelve men with benign pituitary disease causing GH and ACTH deficiency on stable replacement therapy for >6 months were studied after GH withdrawal for 3 weeks, and after either placebo or GH injections were reintroduced for another 3 weeks. We measured cortisol kinetics during 9,11,12,12-2H4-cortisol (d4-cortisol) infusion, urinary cortisol/cortisone metabolite ratios, liver 11β-HSD1 by appearance of plasma cortisol after oral cortisone, and 11β-HSD1 mRNA levels in subcutaneous adipose biopsies. Results GH withdrawal and reintroduction had no effect on 9,12,12-[2H]3-cortisol (d3-cortisol) appearance, urinary cortisol/cortisone metabolite ratios, initial appearance of cortisol after oral cortisone, or adipose 11β-HSD1 mRNA. GH withdrawal increased plasma cortisol 30–180 min after oral cortisone, increased d4-cortisol clearance, and decreased relative excretion of 5α-reduced cortisol metabolites. Conclusions In this setting, GH did not regulate 11β-HSD1 rapidly in vivo in humans. Altered cortisol metabolism with longer term changes in GH may reflect indirect effects on 11β-HSD1. These data do not suggest that glucocorticoid replacement doses need to be increased immediately after introducing GH therapy to compensate for reduced 11β-HSD1 activity, although dose adjustment may be required in the longer term. PMID:19549748

The characterization of six auxin-induced tomato GH3 genes uncovers a member, SlGH3.4, strongly responsive to arbuscular mycorrhizal symbiosis.

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Liao, Dehua; Chen, Xiao; Chen, Aiqun; Wang, Huimin; Liu, Jianjian; Liu, Junli; Gu, Mian; Sun, Shubin; Xu, Guohua

2015-04-01

In plants, the GH3 gene family is widely considered to be involved in a broad range of plant physiological processes, through modulation of hormonal homeostasis. Multiple GH3 genes have been functionally characterized in several plant species; however, to date, limited works to study the GH3 genes in tomato have been reported. Here, we characterize the expression and regulatory profiles of six tomato GH3 genes, SlGH3.2, SlGH3.3, SlGH3.4, SlGH3.7, SlGH3.9 and SlGH3.15, in response to different phytohormone applications and arbuscular mycorrhizal (AM) fungal colonization. All six GH3 genes showed inducible responses to external IAA, and three members were significantly up-regulated in response to AM symbiosis. In particular, SlGH3.4, the transcripts of which were barely detectable under normal growth conditions, was strongly activated in the IAA-treated and AM fungal-colonized roots. A comparison of the SlGH3.4 expression in wild-type plants and M161, a mutant with a defect in AM symbiosis, confirmed that SlGH3.4 expression is highly correlated to mycorrhizal colonization. Histochemical staining demonstrated that a 2,258 bp SlGH3.4 promoter fragment could drive β-glucuronidase (GUS) expression strongly in root tips, steles and cortical cells of IAA-treated roots, but predominantly in the fungal-colonized cells of mycorrhizal roots. A truncated 654 bp promoter failed to direct GUS expression in IAA-treated roots, but maintained the symbiosis-induced activity in mycorrhizal roots. In summary, our results suggest that a mycorrhizal signaling pathway that is at least partially independent of the auxin signaling pathway has evolved for the co-regulation of the auxin- and mycorrhiza-activated GH3 genes in plants. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Serum NT-proCNP levels increased after initiation of GH treatment in patients with achondroplasia/hypochondroplasia.

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Kubota, Takuo; Wang, Wei; Miura, Kohji; Nakayama, Hirofumi; Yamamoto, Keiko; Fujiwara, Makoto; Ohata, Yasuhisa; Tachibana, Makiko; Kitaoka, Taichi; Takakuwa, Satoshi; Miyoshi, Yoko; Namba, Noriyuki; Ozono, Keiichi

2016-06-01

Serum amino-terminal propeptide of C-type natriuretic peptide (NT-proCNP) levels have been proposed as a biomarker of linear growth in healthy children. The usefulness of NT-proCNP in patients with achondroplasia (ACH)/hypochondroplasia (HCH) remains to be elucidated. The objective was to study whether serum NT-proCNP level is a good biomarker for growth in ACH/HCH and other patients of short stature. This was a longitudinal cohort study. Sixteen children with ACH (aged 0·4-4·3 years), six children with HCH (2·7-6·3 years), 23 children with idiopathic short stature (ISS) (2·2-9·0 years), eight short children with GH deficiency (GHD) (2·9-6·8 years) and five short children born small for gestational age (SGA) (2·0-6·6 years). Patients with ACH/HCH received GH treatment for 1 year. Serum NT-proCNP levels and height were measured. NT-proCNP levels positively correlated with height velocity in these short children (P < 0·05, r = 0·27). NT-proCNP levels inversely correlated with age in children with ISS alone (P < 0·01, r = -0·55). Serum NT-proCNP levels in patients with ACH/HCH were increased 3 months following the initiation of GH treatment (P < 0·05). Height SDS gain during GH treatment for 1 year was positively correlated with the changes in NT-proCNP levels after the initiation of GH (P < 0·01, r = 0·72). Serum NT-proCNP levels may be a good biomarker to indicate the effect of GH treatment on growth in patients with ACH/HCH at least in the first year and height velocity in short stature patients. © 2016 John Wiley & Sons Ltd.

The dwarf phenotype in GH240B mice, haploinsufficient for the autism candidate gene Neurobeachin, is caused by ectopic expression of recombinant human growth hormone.

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Nuytens, Kim; Tuand, Krizia; Fu, Quili; Stijnen, Pieter; Pruniau, Vincent; Meulemans, Sandra; Vankelecom, Hugo; Creemers, John W M

2014-01-01

Two knockout mouse models for the autism candidate gene Neurobeachin (Nbea) have been generated independently. Although both models have similar phenotypes, one striking difference is the dwarf phenotype observed in the heterozygous configuration of the GH240B model that is generated by the serendipitous insertion of a promoterless human growth hormone (hGH) genomic fragment in the Nbea gene. In order to elucidate this discrepancy, the dwarfism present in this Nbea mouse model was investigated in detail. The growth deficiency in Nbea+/- mice coincided with an increased percentage of fat mass and a decrease in bone mineral density. Low but detectable levels of hGH were detected in the pituitary and hypothalamus of Nbea+/- mice but not in liver, hippocampus nor in serum. As a consequence, several members of the mouse growth hormone (mGH) signaling cascade showed altered mRNA levels, including a reduction in growth hormone-releasing hormone mRNA in the hypothalamus. Moreover, somatotrope cells were less numerous in the pituitary of Nbea+/- mice and both contained and secreted significantly less mGH resulting in reduced levels of circulating insulin-like growth factor 1. These findings demonstrate that the random integration of the hGH transgene in this mouse model has not only inactivated Nbea but has also resulted in the tissue-specific expression of hGH causing a negative feedback loop, mGH hyposecretion and dwarfism.

Abalation of Ghrelin receptor in leptin-deficient mice has paradoxical effects on glucose homeostasis compared to Ghrelin-abalated Leptin-deficient mice

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Ghrelin is produced predominantly in stomach and is known to be the endogenous ligand of the growth hormone secretagogue receptor (GHSR). Ghrelin is a GH stimulator and an orexigenic hormone. In contrast, leptin is an anorexic hormone, and leptin-deficient ob/ob mice are obese and diabetic. To study...

Effect of GH/IGF-1 on Bone Metabolism and Osteoporsosis

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Vittorio Locatelli

2014-01-01

Full Text Available Background. Growth hormone (GH and insulin-like growth factor (IGF-1 are fundamental in skeletal growth during puberty and bone health throughout life. GH increases tissue formation by acting directly and indirectly on target cells; IGF-1 is a critical mediator of bone growth. Clinical studies reporting the use of GH and IGF-1 in osteoporosis and fracture healing are outlined. Methods. A Pubmed search revealed 39 clinical studies reporting the effects of GH and IGF-1 administration on bone metabolism in osteopenic and osteoporotic human subjects and on bone healing in operated patients with normal GH secretion. Eighteen clinical studies considered the effect with GH treatment, fourteen studies reported the clinical effects with IGF-1 administration, and seven related to the GH/IGF-1 effect on bone healing. Results. Both GH and IGF-1 administration significantly increased bone resorption and bone formation in the most studies. GH/IGF-1 administration in patients with hip or tibial fractures resulted in increased bone healing, rapid clinical improvements. Some conflicting results were evidenced. Conclusions. GH and IGF-1 therapy has a significant anabolic effect. GH administration for the treatment of osteoporosis and bone fractures may greatly improve clinical outcome. GH interacts with sex steroids in the anabolic process. GH resistance process is considered.

Effect of GH/IGF-1 on Bone Metabolism and Osteoporsosis

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Locatelli, Vittorio; Bianchi, Vittorio E.

2014-01-01

Background. Growth hormone (GH) and insulin-like growth factor (IGF-1) are fundamental in skeletal growth during puberty and bone health throughout life. GH increases tissue formation by acting directly and indirectly on target cells; IGF-1 is a critical mediator of bone growth. Clinical studies reporting the use of GH and IGF-1 in osteoporosis and fracture healing are outlined. Methods. A Pubmed search revealed 39 clinical studies reporting the effects of GH and IGF-1 administration on bone metabolism in osteopenic and osteoporotic human subjects and on bone healing in operated patients with normal GH secretion. Eighteen clinical studies considered the effect with GH treatment, fourteen studies reported the clinical effects with IGF-1 administration, and seven related to the GH/IGF-1 effect on bone healing. Results. Both GH and IGF-1 administration significantly increased bone resorption and bone formation in the most studies. GH/IGF-1 administration in patients with hip or tibial fractures resulted in increased bone healing, rapid clinical improvements. Some conflicting results were evidenced. Conclusions. GH and IGF-1 therapy has a significant anabolic effect. GH administration for the treatment of osteoporosis and bone fractures may greatly improve clinical outcome. GH interacts with sex steroids in the anabolic process. GH resistance process is considered. PMID:25147565

GH administration and discontinuation in healthy elderly men

DEFF Research Database (Denmark)

Lange, K H; Isaksson, F; Rasmussen, M H

2001-01-01

GH administration results in increased lean body mass (LBM), decreased fat mass (FM) and increased energy expenditure (EE). GH therapy may therefore have potential benefits, especially in the elderly, who are known to have decreased function of the GH/IGF-I axis. Several studies have focused...... discontinuation on body composition, resting oxygen uptake (VO2), resting heart rate (HR) and GH related serum markers in healthy elderly men....

Effect of cessation of GH treatment on cognition during transition phase in Prader-Willi syndrome: results of a 2-year crossover GH trial.

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Kuppens, R J; Mahabier, E F; Bakker, N E; Siemensma, E P C; Donze, S H; Hokken-Koelega, A C S

2016-11-16

Patients with Prader-Willi syndrome (PWS) have a cognitive impairment. Growth hormone (GH) treatment during childhood improves cognitive functioning, while cognition deteriorates in GH-untreated children with PWS. Cessation of GH treatment at attainment of adult height (AH) might deteriorate their GH-induced improved cognition, while continuation might benefit them. We, therefore, investigated the effects of placebo versus GH administration on cognition in young adults with PWS who were GH-treated for many years during childhood and had attained AH. Two-year, randomized, double-blind, placebo-controlled cross-over study in 25 young adults with PWS. Cross-over intervention with placebo and GH (0.67 mg/m 2 /day), both during 1 year. Total (TIQ), verbal (VIQ) and performance IQ (PIQ) did not deteriorate during 1 year of placebo, compared to GH treatment (p > 0.322). Young adults with a lower TIQ had significantly more loss of TIQ points during placebo versus GH, in particular VIQ decreased more in those with a lower VIQ. The effect of placebo versus GH on TIQ, VIQ and PIQ was not different for gender or genotype. Compared to GH treatment, 1 year of placebo did not deteriorate cognitive functioning of GH-treated young adults with PWS who have attained AH. However, patients with a lower cognitive functioning had more loss in IQ points during placebo versus GH treatment. The reassuring finding that 1 year of placebo does not deteriorate cognitive functioning does, however, not exclude a gradual deterioration of cognitive functioning on the long term. ISRCTN24648386 , NTR1038 , Dutch Trial Register, www.trialregister.nl . Registered 16 August 2007.

The paracrine effect of exogenous growth hormone alleviates dysmorphogenesis caused by tbx5 deficiency in zebrafish (Danio rerio embryos

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Tsai Tzu-Chun

2012-07-01

Full Text Available Abstract Background Dysmorphogenesis and multiple organ defects are well known in zebrafish (Danio rerio embryos with T-box transcription factor 5 (tbx5 deficiencies, mimicking human Holt-Oram syndrome. Methods Using an oligonucleotide-based microarray analysis to study the expression of special genes in tbx5 morphants, we demonstrated that GH and some GH-related genes were markedly downregulated. Zebrafish embryos microinjected with tbx5-morpholino (MO antisense RNA and mismatched antisense RNA in the 1-cell stage served as controls, while zebrafish embryos co-injected with exogenous growth hormone (GH concomitant with tbx5-MO comprised the treatment group. Results The attenuating effects of GH in tbx5-MO knockdown embryos were quantified and observed at 24, 30, 48, 72, and 96 h post-fertilization. Though the understanding of mechanisms involving GH in the tbx5 functioning complex is limited, exogenous GH supplied to tbx5 knockdown zebrafish embryos is able to enhance the expression of downstream mediators in the GH and insulin-like growth factor (IGF-1 pathway, including igf1, ghra, and ghrb, and signal transductors (erk1, akt2, and eventually to correct dysmorphogenesis in various organs including the heart and pectoral fins. Supplementary GH also reduced apoptosis as determined by a TUNEL assay and decreased the expression of apoptosis-related genes and proteins (bcl2 and bad according to semiquantitative reverse-transcription polymerase chain reaction and immunohistochemical analysis, respectively, as well as improving cell cycle-related genes (p27 and cdk2 and cardiomyogenetic genes (amhc, vmhc, and cmlc2. Conclusions Based on our results, tbx5 knockdown causes a pseudo GH deficiency in zebrafish during early embryonic stages, and supplementation of exogenous GH can partially restore dysmorphogenesis, apoptosis, cell growth inhibition, and abnormal cardiomyogenesis in tbx5 knockdown zebrafish in a paracrine manner.

GH replacement therapy and second neoplasms in adult survivors of childhood cancer: a retrospective study from a single institution.

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Brignardello, E; Felicetti, F; Castiglione, A; Fortunati, N; Matarazzo, P; Biasin, E; Sacerdote, C; Ricardi, U; Fagioli, F; Corrias, A; Arvat, E

2015-02-01

Growth hormone deficiency (GHD) is the most common endocrine late effect observed in childhood cancer survivors (CCS) previously submitted to cranial irradiation. Radiation therapy can also increase the risk of second neoplasms (SNs). Since in previous studies GH replacement therapy was associated with increased incidence of neoplasia, we explored the association between SNs and GH replacement therapy in a cohort of CCS with GHD. Within the clinical cohort of CCS referred to the Transition Unit for Childhood Cancer Survivors of Turin between November 2001 and December 2012, we considered all patients who developed GHD as a consequence of cancer therapies. GHD was always diagnosed in childhood. To evaluate the quality of data, our cohort was linked to the Childhood Cancer Registry of Piedmont. GHD was diagnosed in 49 out of 310 CCS included in our clinical cohort. At least one SN was diagnosed in 14 patients, meningioma and basal cell carcinoma being the most common SNs. The cumulative incidence of SNs was similar in GH-treated and -untreated patients (8 SNs out of 26 GH-treated and 6 out of 23 GH-untreated patients; p = 0.331). Age, sex and paediatric cancer type had no impact on SNs development. In our CCS, GH replacement therapy does not seem to increase the risk of SNs. Anyway, independently from replacement therapy, in these patients we observed an elevated risk of SNs, possibly related to previous radiation therapy, which suggests the need of a close long-term follow-up.

Congenital IGF1 deficiency tends to confer protection against post-natal development of malignancies.

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Steuerman, Rachel; Shevah, Orit; Laron, Zvi

2011-04-01

To investigate whether congenital IGF1 deficiency confers protection against development of malignancies, by comparing the prevalence of malignancies in patients with congenital (secondary) deficiency of IGF1 with the prevalence of cancer in their family members. Only patients with an ascertained diagnosis of either Laron syndrome (LS), congenital IGHD, congenital multiple pituitary hormone deficiency (cMPHD) including GH or GHRHR defect were included in this study. In addition to our own patients, we performed a worldwide survey and collected data on a total of 538 patients, 752 of their first-degree family members, of which 274 were siblings and 131 were further family members. We found that none of the 230 LS patients developed cancer and that only 1 out of 116 patients with congenital IGHD, also suffering from xeroderma pigmentosum, had a malignancy. Out of 79 patients with GHRHR defects and out of 113 patients with congenital MPHD, we found three patients with cancer in each group. Among the first-degree family members (most heterozygotes) of LS, IGHD and MPHD, we found 30 cases of cancer and 1 suspected. In addition, 31 malignancies were reported among 131 further relatives. Our findings bear heavily on the relationship between GH/IGF1 and cancer. Homozygous patients with congenital IGF1 deficiency and insensitivity to GH such as LS seem protected from future cancer development, even if treated by IGF1. Patients with congenital IGHD also seem protected.

Effect of cessation of GH treatment on cognition during transition phase in Prader-Willi syndrome: results of a 2-year crossover GH trial

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R. J. Kuppens

2016-11-01

Full Text Available Abstract Background Patients with Prader-Willi syndrome (PWS have a cognitive impairment. Growth hormone (GH treatment during childhood improves cognitive functioning, while cognition deteriorates in GH-untreated children with PWS. Cessation of GH treatment at attainment of adult height (AH might deteriorate their GH-induced improved cognition, while continuation might benefit them. We, therefore, investigated the effects of placebo versus GH administration on cognition in young adults with PWS who were GH-treated for many years during childhood and had attained AH. Method Two-year, randomized, double-blind, placebo-controlled cross-over study in 25 young adults with PWS. Cross-over intervention with placebo and GH (0.67 mg/m2/day, both during 1 year. Results Total (TIQ, verbal (VIQ and performance IQ (PIQ did not deteriorate during 1 year of placebo, compared to GH treatment (p > 0.322. Young adults with a lower TIQ had significantly more loss of TIQ points during placebo versus GH, in particular VIQ decreased more in those with a lower VIQ. The effect of placebo versus GH on TIQ, VIQ and PIQ was not different for gender or genotype. Conclusions Compared to GH treatment, 1 year of placebo did not deteriorate cognitive functioning of GH-treated young adults with PWS who have attained AH. However, patients with a lower cognitive functioning had more loss in IQ points during placebo versus GH treatment. The reassuring finding that 1 year of placebo does not deteriorate cognitive functioning does, however, not exclude a gradual deterioration of cognitive functioning on the long term. Trial registration ISRCTN24648386 , NTR1038 , Dutch Trial Register, www.trialregister.nl . Registered 16 August 2007.

Dose dependency of time of onset of radiation-induced growth hormone deficiency

International Nuclear Information System (INIS)

Clayton, P.E.; Shalet, S.M.

1991-01-01

Growth hormone (GH) secretion during insulin-induced hypoglycemia was assessed on 133 occasions in 82 survivors of childhood malignant disease. All had received cranial irradiation with a dose range to the hypothalamic-pituitary axis of 27 to 47.5 Gy (estimated by a schedule of 16 fractions over 3 weeks) and had been tested on one or more occasions between 0.2 and 18.9 years after treatment. Results of one third of the GH tests were defined as normal (GH peak response, greater than 15 mU/L) within the first 5 years, in comparison with 16% after 5 years. Stepwise multiple linear regression analysis showed that dose (p = 0.007) and time from irradiation (p = 0.03), but not age at therapy, had a significant influence on peak GH responses. The late incidence of GH deficiency was similar over the whole dose range (4 of 26 GH test results normal for less than 30 Gy and 4 of 25 normal for greater than or equal to 30 Gy after 5 years), but the speed of onset over the first years was dependent on dose. We conclude that the requirement for GH replacement therapy and the timing of its introduction will be influenced by the dose of irradiation received by the hypothalamic-pituitary axis

Insulin, IGF-1, and GH Receptors Are Altered in an Adipose Tissue Depot-Specific Manner in Male Mice With Modified GH Action.

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Hjortebjerg, Rikke; Berryman, Darlene E; Comisford, Ross; Frank, Stuart J; List, Edward O; Bjerre, Mette; Frystyk, Jan; Kopchick, John J

2017-05-01

Growth hormone (GH) is a determinant of glucose homeostasis and adipose tissue (AT) function. Using 7-month-old transgenic mice expressing the bovine growth hormone (bGH) gene and growth hormone receptor knockout (GHR-/-) mice, we examined whether changes in GH action affect glucose, insulin, and pyruvate tolerance and AT expression of proteins involved in the interrelated signaling pathways of GH, insulinlike growth factor 1 (IGF-1), and insulin. Furthermore, we searched for AT depot-specific differences in control mice. Glycated hemoglobin levels were reduced in bGH and GHR-/- mice, and bGH mice displayed impaired gluconeogenesis as judged by pyruvate tolerance testing. Serum IGF-1 was elevated by 90% in bGH mice, whereas IGF-1 and insulin were reduced by 97% and 61% in GHR-/- mice, respectively. Igf1 RNA was increased in subcutaneous, epididymal, retroperitoneal, and brown adipose tissue (BAT) depots in bGH mice (mean increase ± standard error of the mean in all five depots, 153% ± 27%) and decreased in all depots in GHR-/- mice (mean decrease, 62% ± 4%). IGF-1 receptor expression was decreased in all AT depots of bGH mice (mean decrease, 49% ± 6%) and increased in all AT depots of GHR-/- mice (mean increase, 94% ± 8%). Insulin receptor expression was reduced in retroperitoneal, mesenteric, and BAT depots in bGH mice (mean decrease in all depots, 56% ± 4%) and augmented in subcutaneous, retroperitoneal, mesenteric, and BAT depots in GHR-/- mice (mean increase: 51% ± 1%). Collectively, our findings indicate a role for GH in influencing hormone signaling in AT in a depot-dependent manner. Copyright © 2017 Endocrine Society.

The GH/IGF axis in the mouse kidney

NARCIS (Netherlands)

V. Cingel-Ristic

2004-01-01

textabstractGrowth hormone (GH) is a protein hormone synthesized and secreted by somatotroph cells within the anterior pituitary predominantly under regulation of hypothalamic peptides, GH releasing hormone (GHRH) and somatostatin (SS) (1-3) (Figure 1). Further, production of GH is modulated by

Evaluation of growth hormone (GH) action in mice: discovery of GH receptor antagonists and clinical indications.

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Kopchick, John J; List, Edward O; Kelder, Bruce; Gosney, Elahu S; Berryman, Darlene E

2014-04-05

The discovery of a growth hormone receptor antagonist (GHA) was initially established via expression of mutated GH genes in transgenic mice. Following this discovery, development of the compound resulted in a drug termed pegvisomant, which has been approved for use in patients with acromegaly. Pegvisomant treatment in a dose dependent manner results in normalization of IGF-1 levels in most patients. Thus, it is a very efficacious and safe drug. Since the GH/IGF-1 axis has been implicated in the progression of several types of cancers, many have suggested the use of pegvisomant as an anti-cancer therapeutic. In this manuscript, we will review the use of mouse strains that possess elevated or depressed levels of GH action for unraveling many of GH actions. Additionally, we will describe experiments in which the GHA was discovered, review results of pegvisomant's preclinical and clinical trials, and provide data suggesting pegvisomant's therapeutic value in selected types of cancer. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Early treatment with GH alone in Turner syndrome: prepubertal catch-up growth and waning effect.

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Wasniewska, Malgorzata; De Luca, Filippo; Bergamaschi, Rosalba; Guarneri, Maria Pia; Mazzanti, Laura; Matarazzo, Patrizia; Petri, Antonella; Crisafulli, Giuseppe; Salzano, Giuseppina; Lombardo, Fortunato

2004-11-01

In order to ascertain the advantages of early GH treatment in Turner syndrome (TS), we started a prospective study aimed at evaluating prepubertal height gain in a cohort of 29 girls who were treated with the same pro-kilo GH dose (1.0 IU/kg per week) since they were less than 6 years old and for at least 5 years before entering puberty. Following a minimum of 6 months of baseline observations, 29 girls with TS were enrolled for this prospective study provided that they (a) were less than 6 years old, (b) were below -1.0 standard deviation score (SDS) for height, (c) had a projected adult height (PAH) lower than the respective target height (TH) and (d) had a height velocity (HV) lower than -1.0 SDS. All the selected girls underwent a 5-year treatment with biosynthetic GH at a stable dose of 1.0 IU/kg per week and were periodically measured during the treatment period in order to evaluate height, HV and PAH. After a dramatic acceleration during the 1st year, HV was attenuated during the subsequent years, reaching its nadir at the 5th year. Height deficiency under therapy progressively decreased from entry onwards, shifting from -2.4+/-0.7 to -1.0+/-1.2 SDS. In the same period, mean PAH progressively increased, although after 5 years it remained lower than the average TH. (a) An effective growth-promoting strategy in TS should be based on early GH treatment, as suggested by our results. (b) This strategy could result in a prepubertal normalization of height, thus allowing the appropriate timing for the induction of puberty. (c) An initial GH dose of 1.0 IU/kg per week may be suitable during the first years of therapy, as shown by our data documenting an important waning effect of GH therapy only after the 4th year of treatment. (d) No acceleration of bone maturation was observed under this treatment regimen.

Arterial pulse wave velocity, inflammatory markers, pathological GH and IGF states, cardiovascular and cerebrovascular disease

Directory of Open Access Journals (Sweden)

Michael R Graham

2008-12-01

Full Text Available Michael R Graham1, Peter Evans2, Bruce Davies1, Julien S Baker11Health and Exercise Science Research Unit, Faculty of Health Sport and Science, University of Glamorgan, Pontypridd, Wales, United Kingdom; 2Royal Gwent Hospital, Newport, Gwent, United KingdomAbstract: Blood pressure (BP measurements provide information regarding risk factors associated with cardiovascular disease, but only in a specific artery. Arterial stiffness (AS can be determined by measurement of arterial pulse wave velocity (APWV. Separate from any role as a surrogate marker, AS is an important determinant of pulse pressure, left ventricular function and coronary artery perfusion pressure. Proximal elastic arteries and peripheral muscular arteries respond differently to aging and to medication. Endogenous human growth hormone (hGH, secreted by the anterior pituitary, peaks during early adulthood, declining at 14% per decade. Levels of insulin-like growth factor-I (IGF-I are at their peak during late adolescence and decline throughout adulthood, mirror imaging GH. Arterial endothelial dysfunction, an accepted cause of increased APWV in GH deficiency (GHD is reversed by recombinant human (rh GH therapy, favorably influencing the risk for atherogenesis. APWV is a noninvasive method for measuring atherosclerotic and hypertensive vascular changes increases with age and atherosclerosis leading to increased systolic blood pressure and increased left ventricular hypertrophy. Aerobic exercise training increases arterial compliance and reduces systolic blood pressure. Whole body arterial compliance is lowered in strength-trained individuals. Homocysteine and C-reactive protein are two infl ammatory markers directly linked with arterial endothelial dysfunction. Reviews of GH in the somatopause have not been favorable and side effects of treatment have marred its use except in classical GHD. Is it possible that we should be assessing the combined effects of therapy with rhGH and rh

GH Therapy and first final height data in Noonan-like syndrome with loose anagen hair (Mazzanti syndrome).

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Mazzanti, Laura; Tamburrino, Federica; Scarano, Emanuela; Perri, Annamaria; Vestrucci, Benedetta; Guidetti, Monica; Rossi, Cesare; Tartaglia, Marco

2013-11-01

Noonan-like syndrome with loose anagen hair (NS/LAH or Mazzanti Syndrome) is caused by a single missense mutation in SHOC2 promoting tN-myristoylation of the encoded protein. Cardinal features include facial features resembling NS, short stature often associated with proven growth hormone deficiency (GHD), typical ectodermal anomalies, and distinctive behavior. Overall, the clinical features are more severe than those generally observed in NS, even though the phenotype improves with age. We report on growth and pubertal trend in seven patients heterozygous for a mutated SHOC2 allele, treated with long-term GH-therapy, and final height (FH) in three of them. They were approximately -3 SDS below the Italian general population standards, they had very low IGF1 levels at baseline and GHD at pharmacological tests. All patients were treated with GH (0.035 mg/kg/day) for a mean period of 8.49 ± 5.72 years. After the 1st year of GH-therapy, IGF1 level and height velocity had increased. Three of 7 patients reached the FH (-2.34 ± 0.12 SDS) at 18.25 ± 0.73 years, after GH administration for 12.39 ± 2.12 years. Pubertal development was variable, showing a prolonged and delayed puberty or rapid pubertal progression that could impair the FH. Overall, our data in this small cohort suggest that NS/LAH patients benefit from long-term GH-therapy, although they do not show the characteristic catch-up growth of isolated GHD. While the observed growth and pubertal behavior is consistent with a dysfunction of the hypothalamic-pituitary-gonadal axis, the functional link between SHOC2 and the GH/IGF signaling pathways remains to be clarified. © 2013 Wiley Periodicals, Inc.

Plasma lactate, GH and GH-binding protein levels in exercise following BCAA supplementation in athletes.

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De Palo, E F; Gatti, R; Cappellin, E; Schiraldi, C; De Palo, C B; Spinella, P

2001-01-01

Branched chain amino acids (BCAA) stimulate protein synthesis, and growth hormone (GH) is a mediator in this process. A pre-exercise BCAA ingestion increases muscle BCAA uptake and use. Therefore after one month of chronic BCAA treatment (0.2 gkg(-1) of body weight), the effects of a pre-exercise oral supplementation of BCAA (9.64 g) on the plasma lactate (La) were examined in triathletes, before and after 60 min of physical exercise (75% of VO2 max). The plasma levels of GH (pGH) and of growth hormone binding protein (pGHBP) were also studied. The end-exercise La of each athlete was higher than basal. Furthermore, after the chronic BCAA treatment, these end-exercise levels were lower than before this treatment (8.6+/-0.8 mmol L(-1) after vs 12.8+/-1.0 mmol L(-1) before treatment; p BCAA chronic treatment, this end-exercise pGHBP was 738+/-85 pmol L(-1) before vs 1691+/-555 pmol L(-1) after. pGH/pGHBP ratio was unchanged in each athlete and between the groups, but a tendency to increase was observed at end-exercise. The lower La at the end of an intense muscular exercise may reflect an improvement of BCAA use, due to the BCAA chronic treatment. The chronic BCAA effects on pGH and pGHBP might suggest an improvement of muscle activity through protein synthesis.

Serum adiponectin levels in adults with Prader-Willi syndrome are independent of anthropometrical parameters and do not change with GH treatment

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Hoybye, Charlotte; Bruun, Jens M; Richelsen, Bjorn

2004-01-01

it of interest to measure adiponectin levels in PWS. PATIENTS AND METHODS: 17 adults, nine men and eight women, 17 to 32 years of age, with a mean body mass index (BMI) of 35+/-3.2 kg/m2 participated. All had clinical PWS. They were randomized to treatment with placebo or GH (Genotropin) for six months......OBJECTIVE: Obesity and growth hormone (GH) deficiency are common in Prader-Willi syndrome (PWS) and these patients are at risk of metabolic diseases in adult life and of reduced life span. Low adiponectin values are associated with obesity and the metabolic syndrome. We therefore found......, and subsequently all received GH for 12 months. At baseline, serum total adiponectin levels in the PWS patients were compared with 25 lean and 34 obese controls. Body composition and various metabolic parameters, including adiponectin, were studied every six months in the PWS group. RESULTS: Serum adiponectin...

The dwarf phenotype in GH240B mice, haploinsufficient for the autism candidate gene Neurobeachin, is caused by ectopic expression of recombinant human growth hormone.

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Kim Nuytens

Full Text Available Two knockout mouse models for the autism candidate gene Neurobeachin (Nbea have been generated independently. Although both models have similar phenotypes, one striking difference is the dwarf phenotype observed in the heterozygous configuration of the GH240B model that is generated by the serendipitous insertion of a promoterless human growth hormone (hGH genomic fragment in the Nbea gene. In order to elucidate this discrepancy, the dwarfism present in this Nbea mouse model was investigated in detail. The growth deficiency in Nbea+/- mice coincided with an increased percentage of fat mass and a decrease in bone mineral density. Low but detectable levels of hGH were detected in the pituitary and hypothalamus of Nbea+/- mice but not in liver, hippocampus nor in serum. As a consequence, several members of the mouse growth hormone (mGH signaling cascade showed altered mRNA levels, including a reduction in growth hormone-releasing hormone mRNA in the hypothalamus. Moreover, somatotrope cells were less numerous in the pituitary of Nbea+/- mice and both contained and secreted significantly less mGH resulting in reduced levels of circulating insulin-like growth factor 1. These findings demonstrate that the random integration of the hGH transgene in this mouse model has not only inactivated Nbea but has also resulted in the tissue-specific expression of hGH causing a negative feedback loop, mGH hyposecretion and dwarfism.

PICK1 deficiency impairs secretory vesicle biogenesis and leads to growth retardation and decreased glucose tolerance.

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Birgitte Holst

Full Text Available Secretory vesicles in endocrine cells store hormones such as growth hormone (GH and insulin before their release into the bloodstream. The molecular mechanisms governing budding of immature secretory vesicles from the trans-Golgi network (TGN and their subsequent maturation remain unclear. Here, we identify the lipid binding BAR (Bin/amphiphysin/Rvs domain protein PICK1 (protein interacting with C kinase 1 as a key component early in the biogenesis of secretory vesicles in GH-producing cells. Both PICK1-deficient Drosophila and mice displayed somatic growth retardation. Growth retardation was rescued in flies by reintroducing PICK1 in neurosecretory cells producing somatotropic peptides. PICK1-deficient mice were characterized by decreased body weight and length, increased fat accumulation, impaired GH secretion, and decreased storage of GH in the pituitary. Decreased GH storage was supported by electron microscopy showing prominent reduction in secretory vesicle number. Evidence was also obtained for impaired insulin secretion associated with decreased glucose tolerance. PICK1 localized in cells to immature secretory vesicles, and the PICK1 BAR domain was shown by live imaging to associate with vesicles budding from the TGN and to possess membrane-sculpting properties in vitro. In mouse pituitary, PICK1 co-localized with the BAR domain protein ICA69, and PICK1 deficiency abolished ICA69 protein expression. In the Drosophila brain, PICK1 and ICA69 co-immunoprecipitated and showed mutually dependent expression. Finally, both in a Drosophila model of type 2 diabetes and in high-fat-diet-induced obese mice, we observed up-regulation of PICK1 mRNA expression. Our findings suggest that PICK1, together with ICA69, is critical during budding of immature secretory vesicles from the TGN and thus for vesicular storage of GH and possibly other hormones. The data link two BAR domain proteins to membrane remodeling processes in the secretory pathway of

Auxological criteria for the diagnosis of GH-dependent short stature and prescription of rGH: problems and pitfalls

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Giulio Gilli

2007-12-01

Full Text Available Recombinant growth hormone (rGH administration is a cornerstone in the treatment of short stature secondary to GH deficit. Since its introduction in the 80s, the population of short patients with an indication to rGH therapy has clearly broadened, probably because of increased awareness by patients and physicians. Since rGH therapy is demanding for patients and expensive, the Italian National Health Service, like other third payers and regulatory authorities, regulates its prescription according to criteria listed in the Nota AIFA 39. This paper illustrates pitfalls and difficulties paediatricians may encounter when assessing short stature patients in order to decide upon the opportunity and possibility to initiate rGH therapy through the exposition of four emblematic, though hypothetical, clinical histories. In the discussion, the Authors highlight some of the most critical points in the formulation of the Nota 39, among which are the lack of clear reference values, neglecting of parental height targets and therapeutic responses, as well as some omissions in methodology specifications.

A single amino acid substitution in the exoplasmic domain of the human growth hormone (GH) receptor confers familial GH resistance (Laron syndrome) with positive GH-binding activity by abolishing receptor homodimerization.

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Duquesnoy, P; Sobrier, M L; Duriez, B; Dastot, F; Buchanan, C R; Savage, M O; Preece, M A; Craescu, C T; Blouquit, Y; Goossens, M

1994-01-01

Growth hormone (GH) elicits a variety of biological activities mainly mediated by the GH receptor (GHR), a transmembrane protein that, based on in vitro studies, seemed to function as a homodimer. To test this hypothesis directly, we investigated patients displaying the classic features of Laron syndrome (familial GH resistance characterized by severe dwarfism and metabolic dysfunction), except for the presence of normal binding activity of the plasma GH-binding protein, a molecule that derives from the exoplasmic-coding domain of the GHR gene. In two unrelated families, the same GHR mutation was identified, resulting in the substitution of a highly conserved aspartate residue by histidine at position 152 (D152H) of the exoplasmic domain, within the postulated interface sequence involved in homodimerization. The recombinant mutated receptor protein was correctly expressed at the plasma membrane. It displayed subnormal GH-binding activity, a finding in agreement with the X-ray crystal structure data inferring this aspartate residue outside the GH-binding domain. However, mAb-based studies suggested the critical role of aspartate 152 in the proper folding of the interface area. We show that a recombinant soluble form of the mutant receptor is unable to dimerize, the D152H substitution also preventing the formation of heterodimers of wild-type and mutant molecules. These results provide in vivo evidence that monomeric receptors are inactive and that receptor dimerization is involved in the primary signalling of the GH-associated growth-promoting and metabolic actions. Images PMID:8137822

Dominant dwarfism in transgenic rats by targeting human growth hormone (GH) expression to hypothalamic GH-releasing factor neurons.

OpenAIRE

Flavell, D M; Wells, T; Wells, S E; Carmignac, D F; Thomas, G B; Robinson, I C

1996-01-01

Expression of human growth hormone (hGH) was targeted to growth hormone-releasing (GRF) neurons in the hypothalamus of transgenic rats. This induced dominant dwarfism by local feedback inhibition of GRF. One line, bearing a single copy of a GRF-hGH transgene, has been characterized in detail, and has been termed Tgr (for Transgenic growth-retarded). hGH was detected by immunocytochemistry in the brain, restricted to the median eminence of the hypothalamus. Low levels were also detected in the...

Energy homeostasis targets chromosomal reconfiguration of the human GH1 locus.

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Vakili, Hana; Jin, Yan; Cattini, Peter A

2014-11-01

Levels of pituitary growth hormone (GH), a metabolic homeostatic factor with strong lipolytic activity, are decreased in obese individuals. GH declines prior to the onset of weight gain in response to excess caloric intake and hyperinsulinemia; however, the mechanism by which GH is reduced is not clear. We used transgenic mice expressing the human GH (hGH) gene, GH1, to assess the effect of high caloric intake on expression as well as the local chromosome structure of the intact GH1 locus. Animals exposed to 3 days of high caloric intake exhibited hyperinsulinemia without hyperglycemia and a decrease in both hGH synthesis and secretion, but no difference in endogenous production of murine GH. Efficient GH1 expression requires a long-range intrachromosomal interaction between remote enhancer sequences and the proximal promoter region through "looping" of intervening chromatin. High caloric intake disrupted this interaction and decreased both histone H3/H4 hyperacetylation and RNA polymerase II occupancy at the GH1 promoter. Incorporation of physical activity muted the effects of excess caloric intake on insulin levels, GH1 promoter hyperacetylation, chromosomal architecture, and expression. These results indicate that energy homeostasis alters postnatal hGH synthesis through dynamic changes in the 3-dimensional chromatin structure of the GH1 locus, including structures required for cell type specificity during development.

GH activity and markers of inflammation

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Andreassen, Mikkel; Frystyk, Jan; Faber, Jens

2012-01-01

The GH/IGF1 axis may modulate inflammatory processes. However, the relationship seems complicated as both pro- and anti-inflammatory effects have been demonstrated.......The GH/IGF1 axis may modulate inflammatory processes. However, the relationship seems complicated as both pro- and anti-inflammatory effects have been demonstrated....

The interaction between growth hormone and the thyroid axis in hypopituitary patients.

LENUS (Irish Health Repository)

Behan, Lucy Ann

2011-03-01

Alterations in the hypothalamo-pituitary-thyroid axis have been reported following growth hormone (GH) administration in both adults and children with and without growth hormone deficiency. Reductions in serum free thyroxine (T4), increased tri-iodothyronine (T3) with or without a reduction in serum thyroid-stimulating hormone secretion have been reported following GH replacement, but there are wide inconsistencies in the literature about these perturbations. The clinical significance of these changes in thyroid function remains uncertain. Some authors report the changes are transient and revert to normal after a few months or longer. However, in adult hypopituitary patients, GH replacement has been reported to unmask central hypothyroidism biochemically in 36-47% of apparently euthyroid patients, necessitating thyroxine replacement and resulting in an attenuation of the benefit of GH replacement on quality of life in those who became biochemically hypothyroid after GH replacement. The group at highest risk are those with organic pituitary disease or multiple pituitary hormone deficiencies. It is therefore prudent to monitor thyroid function in hypopituitary patients starting GH therapy to identify those who will develop clinical and biochemical features of central hypothyroidism, thus facilitating optimal and timely replacement.

The interaction between growth hormone and the thyroid axis in hypopituitary patients.

LENUS (Irish Health Repository)

Behan, Lucy Ann

2012-02-01

Alterations in the hypothalamo-pituitary-thyroid axis have been reported following growth hormone (GH) administration in both adults and children with and without growth hormone deficiency. Reductions in serum free thyroxine (T4), increased tri-iodothyronine (T3) with or without a reduction in serum thyroid-stimulating hormone secretion have been reported following GH replacement, but there are wide inconsistencies in the literature about these perturbations. The clinical significance of these changes in thyroid function remains uncertain. Some authors report the changes are transient and revert to normal after a few months or longer. However, in adult hypopituitary patients, GH replacement has been reported to unmask central hypothyroidism biochemically in 36-47% of apparently euthyroid patients, necessitating thyroxine replacement and resulting in an attenuation of the benefit of GH replacement on quality of life in those who became biochemically hypothyroid after GH replacement. The group at highest risk are those with organic pituitary disease or multiple pituitary hormone deficiencies. It is therefore prudent to monitor thyroid function in hypopituitary patients starting GH therapy to identify those who will develop clinical and biochemical features of central hypothyroidism, thus facilitating optimal and timely replacement.

Efficacy of growth hormone therapy in adults with childhood-onset growth hormone deficiency

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Ja Hye Kim

2014-03-01

Full Text Available PurposeGrowth hormone (GH plays a key role in the regulation of body composition, lipid metabolism, and quality of life in adults with GH deficiency (GHD. This study investigated changes in laboratory findings and body composition after GH recommencement for adult GHD and analyzed correlation between GH interruption period and endocrine or anthropometric parameters.MethodsA total of 45 patients (17 females and 28 males diagnosed with childhood-onset GHD (CO-GHD were investigated and all patients had organic brain lesions. Patients diagnosed CO-GHD were retested to confirm adult GHD at age 20.4±5.0 years (18.0-32.1 years. Recombinant human GH was administered at a dose of 0.44 mg/day. Clinical and laboratory parameters such as weight, height, body mass index (BMI, serum insulin-like growth factor 1 (IGF-1, serum total cholesterol, high-density lipoprotein (HDL cholesterol, low-density lipoprotein (LDL cholesterol, and triglyceride levels, were compared between baseline and 12 months after treatment using paired t-test. In addition, correlation between GH interruption period and clinical parameters including BMI, lipid profile, IGF-1, and IGFBP-3, was analyzed.ResultsOf 45 patients, 33 patients had GH interruption period of 4.3±3.6 years (0.7-12.5 years. Serum HDL-cholesterol level increased significantly, whereas LDL-cholesterol decreased after 1 year of GH replacement therapy. However, body weight and BMI showed no significant changes after 1 year of GH replacement therapy. There were no significant correlations between GH interruption period and lipid profile or anthropometric parameters.ConclusionBMI and body weight were not affected by GH replacement. However, GH replacement in adults with GHD offers benefits in lipid metabolism.

Microarchitecture, but Not Bone Mechanical Properties, Is Rescued with Growth Hormone Treatment in a Mouse Model of Growth Hormone Deficiency

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Erika Kristensen

2012-01-01

Full Text Available Growth hormone (GH deficiency is related to an increased fracture risk although it is not clear if this is due to compromised bone quality or a small bone size. We investigated the relationship between bone macrostructure, microarchitecture and mechanical properties in a GH-deficient (GHD mouse model undergoing GH treatment commencing at an early (prepubertal or late (postpubertal time point. Microcomputed tomography images of the femur and L4 vertebra were obtained to quantify macrostructure and vertebral trabecular microarchitecture, and mechanical properties were determined using finite element analyses. In the GHD animals, bone macrostructure was 25 to 43% smaller as compared to the GH-sufficient (GHS controls (P<0.001. GHD animals had 20% and 19% reductions in bone volume ratio (BV/TV and trabecular thickness (Tb.Th, respectively. Whole bone mechanical properties of the GHD mice were lower at the femur and vertebra (67% and 45% resp. than the GHS controls (P<0.001. Both early and late GH treatment partially recovered the bone macrostructure (15 to 32 % smaller than GHS controls and the whole bone mechanical properties (24 to 43% larger than GHD animals although there remained a sustained 27–52% net deficit compared to normal mice (P<0.05. Importantly, early treatment with GH led to a recovery of BV/TV and Tb.Th with a concomitant improvement of trabecular mechanical properties. Therefore, the results suggest that GH treatment should start early, and that measurements of microarchitecture should be considered in the management of GHD.

Timing of growth hormone treatment affects trabecular bone microarchitecture and mineralization in growth hormone deficient mice.

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Kristensen, Erika; Hallgrímsson, Benedikt; Morck, Douglas W; Boyd, Steven K

2010-08-01

Growth hormone (GH) is essential in the development of bone mass, and a growth hormone deficiency (GHD) in childhood is frequently treated with daily injections of GH. It is not clear what effect GHD and its treatment has on bone. It was hypothesized that GHD would result in impaired microarchitecture, and an early onset of treatment would result in a better recovery than late onset. Growth hormone deficient homozygous (lit/lit) mice of both sexes were divided into two treatment groups receiving daily injections of GH, starting at an early (21 days of age) or a late time point (35 days of age, corresponding to the end of puberty). A group of heterozygous mice with normal levels of growth hormone served as controls. In vivo micro-computed tomography scans of the fourth lumbar vertebra were obtained at five time points between 21 and 60 days of age, and trabecular morphology and volumetric BMD were analyzed to determine the effects of GH on bone microarchitecture. Early GH treatment led to significant improvements in bone volume ratio (p=0.006), tissue mineral density (p=0.005), and structure model index (p=0.004) by the study endpoint (day 60), with no detected change in trabecular thickness. Trabecular number increased and trabecular separation decreased in GHD mice regardless of treatment compared to heterozygous mice. This suggests fundamental differences in the structure of trabecular bone in GHD and GH treated mice, reflected by an increased number of thinner trabeculae in these mice compared to heterozygous controls. There were no significant differences between the late treatment group and GHD mice except for connectivity density. Taken together, these results indicate that bone responds to GH treatment initiated before puberty but not to treatment commencing post-puberty, and that GH treatment does not rescue the structure of trabecular bone to that of heterozygous controls. Copyright 2010 Elsevier Inc. All rights reserved.

Human conditions of insulin-like growth factor-I (IGF-I) deficiency

Science.gov (United States)

2012-01-01

Insulin-like growth factor I (IGF-I) is a polypeptide hormone produced mainly by the liver in response to the endocrine GH stimulus, but it is also secreted by multiple tissues for autocrine/paracrine purposes. IGF-I is partly responsible for systemic GH activities although it possesses a wide number of own properties (anabolic, antioxidant, anti-inflammatory and cytoprotective actions). IGF-I is a closely regulated hormone. Consequently, its logical therapeutical applications seems to be limited to restore physiological circulating levels in order to recover the clinical consequences of IGF-I deficiency, conditions where, despite continuous discrepancies, IGF-I treatment has never been related to oncogenesis. Currently the best characterized conditions of IGF-I deficiency are Laron Syndrome, in children; liver cirrhosis, in adults; aging including age-related-cardiovascular and neurological diseases; and more recently, intrauterine growth restriction. The aim of this review is to summarize the increasing list of roles of IGF-I, both in physiological and pathological conditions, underlying that its potential therapeutical options seem to be limited to those proven states of local or systemic IGF-I deficiency as a replacement treatment, rather than increasing its level upper the normal range. PMID:23148873

Human conditions of insulin-like growth factor-I (IGF-I deficiency

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Puche Juan E

2012-11-01

Full Text Available Abstract Insulin-like growth factor I (IGF-I is a polypeptide hormone produced mainly by the liver in response to the endocrine GH stimulus, but it is also secreted by multiple tissues for autocrine/paracrine purposes. IGF-I is partly responsible for systemic GH activities although it possesses a wide number of own properties (anabolic, antioxidant, anti-inflammatory and cytoprotective actions. IGF-I is a closely regulated hormone. Consequently, its logical therapeutical applications seems to be limited to restore physiological circulating levels in order to recover the clinical consequences of IGF-I deficiency, conditions where, despite continuous discrepancies, IGF-I treatment has never been related to oncogenesis. Currently the best characterized conditions of IGF-I deficiency are Laron Syndrome, in children; liver cirrhosis, in adults; aging including age-related-cardiovascular and neurological diseases; and more recently, intrauterine growth restriction. The aim of this review is to summarize the increasing list of roles of IGF-I, both in physiological and pathological conditions, underlying that its potential therapeutical options seem to be limited to those proven states of local or systemic IGF-I deficiency as a replacement treatment, rather than increasing its level upper the normal range.

Effect of cessation of GH treatment on cognition during transition phase in Prader-Willi syndrome: Results of a 2-year crossover GH trial

NARCIS (Netherlands)

R.J. Kuppens (Renske); Mahabier, E.F.; N.E. Bakker (Nienke); E.P.C. Siemensma (Elbrich); S.H. Donze (Stephanie); A.C.S. Hokken-Koelega (Anita)

2016-01-01

textabstractBackground: Patients with Prader-Willi syndrome (PWS) have a cognitive impairment. Growth hormone (GH) treatment during childhood improves cognitive functioning, while cognition deteriorates in GH-untreated children with PWS. Cessation of GH treatment at attainment of adult height (AH)

Body composition in untreated adult patients with Laron syndrome (primary GH insensitivity).

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Laron, Zvi; Ginsberg, Shira; Lilos, Pearl; Arbiv, Mira; Vaisman, Nahum

2006-07-01

To quantify body adiposity and its distribution in untreated adult patients with Laron syndrome (LS; primary GH insensitivity) caused by molecular defects of the GH receptor gene or postreceptor pathways and characterized by dwarfism, obesity, insulin resistance and hyperlipidaemia. Eleven LS patients (seven females and four males) aged 28-53 years were studied. Seven healthy males and six healthy females served as controls. Body composition of the total body trunk, upper and lower extremities was determined using dual-energy X-ray absorptiometry (DEXA). Statistical analysis using an analysis of variance (anova) and Mann-Whitney nonparametric methods was performed separately in males and females. Percentage body fat in the LS patients was much higher (P < 0.01) than that in the control population and the female LS patients were significantly more obese (59% total body fat) than the male patients (39% total body fat) (P < 0.002). It was also evident that in these types of patients with markedly increased body fat and decreased muscle and bone mass, body mass index (BMI) does not accurately reflect the body composition. Lifelong congenital IGF-I deficiency leads to extreme adiposity.

Focus on growth hormone deficiency and bone in adults.

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Tritos, Nicholas A

2017-02-01

Growth hormone (GH) exerts several effects on the skeleton, mediated either directly or indirectly, leading to increased bone formation and resorption rates. Patients with growth hormone deficiency (GHD) of adult onset have decreased bone mineral density (BMD) and increased fracture risk. Some, but not all, studies have found that adults with childhood onset GHD also have lower BMD than healthy controls. Adults with GHD of childhood onset have smaller bone dimensions, leading to possible underestimation of areal BMD (measured by dual energy X-ray absorptiometry), thus potentially confounding the interpretation of densitometric data. Available data suggest that patients with childhood onset GHD are at increased fracture risk. Prospective studies and some clinical trials found that GH replacement for at least 18-24 months leads to increased BMD. Retrospective and prospective data suggest that GH replacement is associated with decreased fracture risk in adults. However, data from randomized clinical trials are lacking. Copyright © 2017 Elsevier Ltd. All rights reserved.

The GH/IGF-1 axis in ageing and longevity

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List, Edward O.; Berryman, Darlene E.; Murrey, John W.

2014-01-01

Secretion of growth hormone (GH), and consequently that of insulin-like growth factor 1 (IGF-1), declines over time until only low levels can be detected in individuals aged ≥60 years. This phenomenon, which is known as the ‘somatopause’, has led to recombinant human GH being widely promoted and abused as an antiageing drug, despite lack of evidence of efficacy. By contrast, several mutations that decrease the tone of the GH/IGF-1 axis are associated with extended longevity in mice. In humans, corresponding or similar mutations have been identified, but whether these mutations alter longevity has yet to be established. The powerful effect of reduced GH activity on lifespan extension in mice has generated the hypothesis that pharmaceutically inhibiting, rather than increasing, GH action might delay ageing. Moreover, mice as well as humans with reduced activity of the GH/IGF-1 axis are protected from cancer and diabetes mellitus, two major ageing-related morbidities. Here, we review data on mouse strains with alterations in the GH/IGF-1 axis and their effects on lifespan. The outcome of corresponding or similar mutations in humans is described, as well as the potential mechanisms underlying increased longevity and the therapeutic benefits and risks of medical disruption of the GH/IGF-1 axis in humans. PMID:23591370

Growth hormone (GH) effects on bone and collagen turnover in healthy adults and its potential as a marker of GH abuse in sports: a double blind, placebo-controlled study. The GH-2000 Study Group.

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Longobardi, S; Keay, N; Ehrnborg, C; Cittadini, A; Rosén, T; Dall, R; Boroujerdi, M A; Bassett, E E; Healy, M L; Pentecost, C; Wallace, J D; Powrie, J; Jørgensen, J O; Saccà, L

2000-04-01

The effects of GH on bone remodeling in healthy adults have not been systematically investigated. An analysis of these effects might provide insights into GH physiology and might yield data useful for the detection of GH doping in sports. The aim of this study was to evaluate the effects of GH administration on biochemical markers of bone and collagen turnover in healthy volunteers. Ninety-nine healthy volunteers of both sexes were enrolled in a multicenter, randomized, double blind, placebo-controlled study and assigned to receive either placebo (40 subjects) or recombinant human GH (0.1 IU/kg day in 29 subjects and 0.2 IU/kg x day in 30 subjects). The treatment duration was 28 days, followed by a 56-day wash-out period. The biochemical markers evaluated were the bone formation markers osteocalcin and C-terminal propeptide of type I procollagen, the resorption marker type I collagen telopeptide, and the soft tissue marker procollagen type III. All variables increased on days 21 and 28 in the two active treatment groups vs. levels in both the baseline (P < 0.01) and placebo (P < 0.01) groups. The increment was more pronounced in the 0.2 IU/kg-day group and remained significant on day 84 for procollagen type III (from 0.53 +/- 0.13 to 0.61 +/- 0.14 kU/L; P < 0.02) and osteocalcin (from 12.2 + 2.9 to 14.6 +/- 3.6 UG/L; P < 0.02), whereas levels of C-terminal propeptide of type I procollagen and type I collagen telopeptide declined after day 42 and were no longer significantly above baseline on day 84 (from 3.9 +/- 1.2 to 5.1 +/-1.5 microg/L and from 174 +/- 60 to 173 +/- 53 microg/L, respectively). Gender-related differences were observed in the study; females were less responsive than males to GH administration with respect to procollagen type III and type I collagen telopeptide (P < 0.001). In conclusion, exogenous GH administration affects the biochemical parameters of bone and collagen turnover in a dose- and gender-dependent manner. As GH-induced modifications

Management of endocrine disease: GH excess: diagnosis and medical therapy

DEFF Research Database (Denmark)

Andersen, Marianne

2014-01-01

Acromegaly is predominantly caused by a pituitary adenoma, which secretes an excess of GH resulting in increased IGF-I levels. Most of the GH assays used currently measure only the 22 kDa form of GH. In theory, the diagnostic sensitivity may be lower compared to the previous assays, which used...... polyclonal antibodies. Many GH-secreting adenomas are plurihormonal and may co-secrete prolactin, TSH and α-subunit. Hyperprolactinemia is found in 30-40% of patients with acromegaly and hyperprolactinemia may occasionally be diagnosed before acromegaly is apparent.Although trans-sphenoidal surgery of a GH......-secreting adenoma remains the first treatment at most centres, the role of somatostatin analogues, octreotide LAR and lanreotide Autogel, as primary therapy is still the subject of some debate. While normalization of GH and IGF-I levels is the main objective in all patients with acromegaly, GH and IGF-I levels may...

Requirement of tyrosine residues 333 and 338 of the growth hormone (GH) receptor for selected GH-stimulated function

DEFF Research Database (Denmark)

Lobie, P E; Allevato, G; Norstedt, G

1995-01-01

We have examined the involvement of tyrosine residues 333 and 338 of the growth hormone (GH) receptor in the cellular response to GH. Stable Chinese hamster ovary (CHO) cell clones expressing a receptor with tyrosine residues at position 333 and 338 of the receptor substituted for phenylalanine (...

Effects of Huang Bai (Phellodendri Cortex and Three Other Herbs on GnRH and GH Levels in GT1–7 and GH3 Cells

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Sun Haeng Lee

2016-01-01

Full Text Available The present study was to evaluate the effects of Huang Bai, Zhi Mu, Mai Ya, and Xia Ku Cao on hormone using the GT1–7 and GH3 cells. The GT1–7 and GH3 cell lines were incubated with DW; DMSO; and 30, 100, or 300 μg/mL of one of the four extract solutions in serum-free media for 24 hours. The MTT assay was performed to determine the cytotoxicity of the four herbs. The GT1–7 and GH3 cells were incubated in DW, estradiol (GT1–7 only, or noncytotoxic herb solutions in serum-free medium for 24 hours. A quantitative RT-PCR and western blot were performed to measure the GnRH expression in GT1–7 cells and GH expression in GH3 cells. Huang Bai, Zhi Mu, Xia Ku Cao, and Mai Ya inhibited the GnRH mRNA expression in GT1–7 cells, whereas Huang Bai enhanced GH mRNA expression in GH3 cells. Additionally, Xia Ku Cao inhibited GnRH protein expression in GT1–7 cells and Huang Bai promoted GH protein expression in GH3 cells. The findings suggest that Huang Bai can delay puberty by inhibiting GnRH synthesis in the hypothalamus while also accelerating growth by promoting GH synthesis and secretion in the pituitary.

Changes in growth hormone (GH) messenger RNA (GH mRNA) expression in the rat anterior pituitary after single interferon (IFN) alpha administration

International Nuclear Information System (INIS)

Romanowski, W.; Braczkowski, R.; Nowakowska-Zajdel, E.; Muc-Wierzgon, M.; Zubelewicz-Szkodzinska, B.; Kosiewicz, J.; Korzonek, I.

2006-01-01

Introduction: Interferon a (IFN-a) is a cytokine with pleiotropic effects which, via different pathways, influences the secretion of certain cytokines and hormones. Growth hormone (GH) secreted from the pituitary has physiological effects on various target tissues. The question is how IFN-a administered in various types of disease influences GH secretion. This study investigated the acute effect of IFN-a on GH mRNA expression in the rat anterior pituitary. Objective: The aim of the study was to measure the cellular expression of GH mRNA by in situ hybridisation in the anterior pituitary after a single administration of IFN-a. Material and methods: Rats were administered an intraperitoneal injection of IFN-a or saline. The rat pituitaries were taken 2 and 4 hours after IFN/saline administration and kept frozen until in situ hybridisation histochemistry. A 31 - base 35S -labelled oligonucleotide probe complementary to part of the exonic mRNA sequence coding for GH mRNA was used. All control and experimental sections were hybridised in the same hybridisation reaction. Results: Acute administration of interferon a increased GH mRNA expression in the anterior pituitary in the 4-hour group in comparison with the control group, and there was no difference between the control group and the 2-hour rats. Conclusion: A single IFN-a administration was found to exert an influence on anterior pituitary GH mRNA expression. These observations may pave the way for presenting a possible new action of IFN-a. (author) GH mRNA, anterior pituitary, interferon

LACTASE DEFICIENCY IN BABIES AND INFANTS

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E.A. Kornienko

2006-01-01

Full Text Available Lactose, the constituent disaccharide of milk and other dairy products, is an important nutrient in early childhood. Lactase breaks down lactose in small intestine. In most people the activity of lactase reduces with age. In infancy lactase deficiency tends to be either transient, which is more often, or secondary to intestinal diseases. Abdominal cramps, anxiety and dyspepsia are the common symptoms of lactase deficiency. Tactics of treatment should take into account a cause and severity of the condition. A specialized milk formula «enfamil lactofree», distinguished for its' optimal formulation, high clinical effectiveness and good tolerance, could be recommended for use in children with primary, transient and secondary lactase deficiency who receive formula and mixed feeding.Key words: lactose, lactase deficiency, lactose-free formula.

Design of the Growth hormone deficiency and Efficacy of Treatment (GET) score and non-interventional proof of concept study.

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Kann, Peter H; Bergmann, Simona; Bidlingmaier, Martin; Dimopoulou, Christina; Pedersen, Birgitte T; Stalla, Günter K; Weber, Matthias M; Meckes-Ferber, Stefanie

2018-02-13

The adverse effects of growth hormone (GH) deficiency (GHD) in adults (AGHD) on metabolism and health-related quality of life (HRQoL) can be improved with GH substitution. This investigation aimed to design a score summarising the features of GHD and evaluate its ability to measure the effect of GH substitution in AGHD. The Growth hormone deficiency and Efficacy of Treatment (GET) score (0-100 points) assessed (weighting): HRQoL (40%), disease-related days off work (10%), bone mineral density (20%), waist circumference (10%), low-density lipoprotein cholesterol (10%) and body fat mass (10%). A prospective, non-interventional, multicentre proof-of-concept study investigated whether the score could distinguish between untreated and GH-treated patients with AGHD. A 10-point difference in GET score during a 2-year study period was expected based on pre-existing knowledge of the effect of GH substitution in AGHD. Of 106 patients eligible for analysis, 22 were untreated GHD controls (9 females, mean ± SD age 52 ± 17 years; 13 males, 57 ± 13 years) and 84 were GH-treated (31 females, age 45 ± 13 years, GH dose 0.30 ± 0.16 mg/day; 53 males, age 49 ± 15 years, GH dose 0.25 ± 0.10 mg/day). Follow-up was 706 ± 258 days in females and 653 ± 242 days in males. The GET score differed between the untreated control and treated groups with a least squares mean difference of + 10.01 ± 4.01 (p = 0.0145). The GET score appeared to be a suitable integrative instrument to summarise the clinical features of GHD and measure the effects of GH substitution in adults. Exercise capacity and muscle strength/body muscle mass could be included in the GET score. NCT number: NCT00934063 . Date of registration: 02 July 2009.

Gitelman syndrome combined with complete growth hormone deficiency

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Se Ra Min

2013-03-01

Full Text Available Gitelman syndrome is a rare autosomal recessive hereditary salt-losing tubulopathy, that manifests as hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. It is caused by mutations in the solute carrier family 12(sodium/chloride transporters, member 3 (SLC12A3 gene encoding the thiazide-sensitive sodium chloride cotransporter channel (NCCT in the distal convoluted tubule of the kidney. It is associated with muscle weakness, cramps, tetany, vomiting, diarrhea, abdominal pain, and growth retardation. The incidence of growth retardation, the exact cause of which is unknown, is lower than that of Bartter syndrome. Herein, we discuss the case of an overweight 12.9-year-old girl of short stature presenting with hypokalemic metabolic alkalosis. The patient, on the basis of detection of a heterozygous mutation in the SLC12A3 gene and poor growth hormone (GH responses in two provocative tests, was diagnosed with Gitelman syndrome combined with complete GH deficiency. GH treatment accompanied by magnesium oxide and potassium replacement was associated with a good clinical response.

Expression of Lymphocyte-derived Growth Hormone (GH) and GH-releasing Hormone Receptors in Aging Rats

OpenAIRE

Weigent, Douglas A.

2013-01-01

In the present study, we show that higher levels of lymphocyte GH are expressed in spleen cells from aging animals compared to young animals. Further, leukocytes from primary and secondary immune tissues and splenic T and B cells from aging rats all express higher levels of GHRH receptors compared to younger animals. Bone marrow and splenic T cells express the highest levels of GHRH receptor in aging animals. Spleen cells from aging animals showed no significant change in proliferation or GH ...

GhZFP1, a novel CCCH-type zinc finger protein from cotton, enhances salt stress tolerance and fungal disease resistance in transgenic tobacco by interacting with GZIRD21A and GZIPR5.

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Guo, Ying-Hui; Yu, Yue-Ping; Wang, Dong; Wu, Chang-Ai; Yang, Guo-Dong; Huang, Jin-Guang; Zheng, Cheng-Chao

2009-01-01

* Zinc finger proteins are a superfamily involved in many aspects of plant growth and development. However, CCCH-type zinc finger proteins involved in plant stress tolerance are poorly understood. * A cDNA clone designated Gossypium hirsutum zinc finger protein 1 (GhZFP1), which encodes a novel CCCH-type zinc finger protein, was isolated from a salt-induced cotton (G. hirsutum) cDNA library using differential hybridization screening and further studied in transgenic tobacco Nicotiana tabacum cv. NC89. Using yeast two-hybrid screening (Y2H), proteins GZIRD21A (GhZFP1 interacting and responsive to dehydration protein 21A) and GZIPR5 (GhZFP1 interacting and pathogenesis-related protein 5), which interacted with GhZFP1, were isolated. * GhZFP1 contains two typical zinc finger motifs (Cx8Cx5Cx3H and Cx5Cx4Cx3H), a putative nuclear export sequence (NES) and a potential nuclear localization signal (NLS). Transient expression analysis using a GhZFP1::GFP fusion gene in onion epidermal cells indicated a nuclear localization for GhZFP1. RNA blot analysis showed that the GhZFP1 transcript was induced by salt (NaCl), drought and salicylic acid (SA). The regions in GhZFP1 that interact with GZIRD21A and GZIPR5 were identified using truncation mutations. * Overexpression of GhZFP1 in transgenic tobacco enhanced tolerance to salt stress and resistance to Rhizoctonia solani. Therefore, it appears that GhZFP1 might be involved as an important regulator in plant responses to abiotic and biotic stresses.

The challenge of growth hormone deficiency (GHD diagnosis and treatment during the transition from puberty into adulthood

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Stefano eCianfarani

2013-03-01

Full Text Available In children with childhood-onset growth hormone deficiency, replacement GH therapy is effective in normalising height during childhood and achieving adult height within the genetic target range. GH has further beneficial effects on body composition and metabolism through adult life. The transition phase, defined as the period from mid to late teens until 6–7 years after the achievement of final height, represents a crucial time for reassessing children’s GH secretion and deciding whether GH therapy should be continued throughout life. Evidence-based guidelines for diagnosis and treatment of GHD children during transition are lacking. The aim of this review is to critically review the up-to-date evidence on the best management of transition patients in order to ensure the correct definitive diagnosis and establish the appropriate therapeutic regimen.

Valutazione di efficienza nella somministrazione dell’ormone della crescita (GH

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Federico Spandonaro

2013-03-01

Full Text Available Treatment with growth hormone (somatropin is effective in six different medical conditions: growth hormone deficiency (GHD, Turner syndrome (TS, growth retardation in children born small for gestational age (SGA, Prader-Willi syndrome (PWS, growth retardation due to chronic renal insufficiency (CRI, growth retardation associated with a deficiency of the gene SHOX (Short Stature HOmeoboXContaining gene. The treatment proved to be also effective in adults who have an impaired growth hormone (acquired in adulthood or childhood.The growth hormone (GH is generally cost effective and, therefore, is usually reimbursed by public health services. In financial terms, GH is a major cost item for health systems. According to the Report OSMED 2010, GH ranks first in Italy between systemic hormonal preparations, excluding sex hormones, distributed by public system, with an annual value of approximately € 88 million (+ 12.7% compared to 2009.Considering the increasing need to control pharmaceutical expenditure, there is a strong interest for the efficient supply of the hormone by the regional health service. From this point of view, the comparison of the specialties on the market is normally carried out on the basis of the cost per mg; this approach, also used in the main studies of cost-effectiveness, is derived from a logic of cost minimization, but it may still be distorting, not taking into account the efficiency of devices used for the administration of the hormone.The proposed analysis verifies the efficiency of different available devices, evaluating the potential waste of product, depending both on the device used and on the characteristics of the population exposed to the treatment.Only in the case of single-dose and disposable formulations is theoretically possible to have zero waste and thus an equivalence between the actual cost of the treatment and the price charged. In other cases, the inefficiency causes a deviation between the actual cost and

Growth hormone (GH) differentially regulates NF-kB activity in preadipocytes and macrophages: implications for GH's role in adipose tissue homeostasis in obesity.

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Kumar, P Anil; Chitra, P Swathi; Lu, Chunxia; Sobhanaditya, J; Menon, Ram

2014-06-01

Adipose tissue remodeling in obesity involves macrophage infiltration and chronic inflammation. NF-kB-mediated chronic inflammation of the adipose tissue is directly implicated in obesity-associated insulin resistance. We have investigated the effect of growth hormone (GH) on NF-kB activity in preadipocytes (3T3-F442A) and macrophages (J774A.1). Our studies indicate that whereas GH increases NF-kB activity in preadipocytes, it decreases NF-kB activity in macrophages. This differential response of NF-kB activity to GH correlates with the GH-dependent expression of a cadre of NF-kB-activated cytokines in these two cell types. Activation of NF-kB by GH in preadipocytes heightens inflammatory response by stimulating production of multiple cytokines including TNF-α, IL-6, and MCP-1, the mediators of both local and systemic insulin resistance and chemokines that recruit macrophages. Our studies also suggest differential regulation of miR132 and SIRT1 expression as a mechanism underlying the observed variance in GH-dependent NF-kB activity and altered cytokine profile in preadipocytes and macrophages. These findings further our understanding of the complex actions of GH on adipocytes and insulin sensitivity.

A patient with Bartter syndrome accompanying severe growth hormone deficiency and focal segmental glomerulosclerosis.

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Akil, Ipek; Ozen, Serkan; Kandiloglu, Ali Riza; Ersoy, Betul

2010-06-01

Bartter syndrome is a rare autosomal recessive, salt-losing disorder characterized by hypokalemic hypochloremic metabolic alkalosis. A 10-year-old boy had severe growth retardation (height standard deviation score -8.15). He had a thin, triangular face, prominent ears and forehead, and big eyes. Megacystis, bilateral hydroureteronephrosis, and residual urine were detected in ultrasonography, but there was no vesicoureteral reflux. Lumbosacral magnetic resonance (MR) showed posterior disc bulging at L4-5. Serum sodium and chloride levels were normal, but mild hypokalemia was overlooked initially. During follow-up, hypokalemic hypochloremic metabolic alkalosis developed, with high urinary chloride and potassium excretion (52 and 43 mEq/L, respectively). The patient, with renal salt loss, was thought to have classic Bartter syndrome due to absence of nephrocalcinosis, presence of persistent hypercalciuria and sensorineural deafness, and presence of relatively mild clinical and laboratory findings, except polyuria initially. The child was treated with indomethacin, spironolactone, and oral potassium in addition to growth hormone (GH). During treatment, he had considerable increase in weight and height compared with the period of GH therapy only. We present this case because, although growth retardation is a major feature of Bartter syndrome, associated GH deficiency is rarely reported in the literature. Diagnosis of Bartter syndrome was made later, as our patient was followed for megacystis and megaureter secondary to the neurogenic bladder and GH deficiency initially; and proteinuria associated with focal segmental glomerulosclerosis responded to treatment for Bartter syndrome.

Growth hormone receptor deficiency in Ecuador: clinical and biochemical phenotype in two populations.

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Guevara-Aguirre, J; Rosenbloom, A L; Fielder, P J; Diamond, F B; Rosenfeld, R G

1993-02-01

We have identified 56 patients with GH receptor deficiency (Laron syndrome) from two provinces in southern Ecuador, one group of 26 (Loja province) with a 4:1 female predominance and 30 patients from neighboring El Oro province with a normal sex ratio. There were no significant differences between the Loja and El Oro populations in stature (-5.3 to -11.5 standard deviation score), other auxologic measures, or in biochemical measures. GH binding protein, the circulating extracellular domain of the GH receptor, was measured by ligand immunofunction assay and found to be comparably low in children and adults. Levels of insulin-like growth factor (IGF)-I and -II and the GH-dependent IGF binding protein-3 (measured by RIA) were significantly greater, and GH and IGF binding protein-2 levels significantly lower in adults than children. Levels of IGF-I (adults) and IGF binding protein-3 (children and adults) correlated inversely with statural deviation from normal (P < 0.01). School performance was at an exceptionally high level, 41 out of 47 who had attended school being in the top 3 in classes of 15-50 persons.

Treatment of growth failure in the absence of GH signaling: The Ecuadorian experience.

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Guevara-Aguirre, Jaime; Guevara, Alexandra; Guevara, Carolina

2018-02-01

Recombinant human insulin-like growth factor-1 (rhIGF-1) treatment studies of growth failure in absence of growth hormone (GH) signaling (GH insensitivity -GHI, Laron syndrome -LS, GH Receptor deficiency -GHRD) have taken place in many locations around the globe. Results from these trials are comparable, and slight differences reported can be attributed to specific circumstances at different research sites. rhIGF-I treatment studies of GHI in Ecuador included various trials performed on children belonging to the largest and only homogeneous cohort of subjects with this condition in the world. All trials were performed by the same team of investigators and, during study periods, subjects received similar nutritional, physical activity and medical advice. Combination of these inherent conditions most likely creates less sources of variability during the research process. Indeed, diagnosis, selection and inclusion of research subjects; methodology used; transport, storage and delivery of study drug; data collection, monitoring and auditing; data analysis, discussion of results, conclusion inferences and reporting, etc., were submitted to the same sources of error. For the above-mentioned reasons, we are hereby mainly covering conclusions derived from rhIGF-I treatment studies of Ecuadorian children whit GHRD due to homozygosity of a splice site mutation occurring at GHR gene, whose unaffected parents were both heterozygous for the same mutation. We also describe studies of rhIGF-I administration in adolescent and adult subjects with GHRD, from the same cohort and with the same genetic anomaly. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prevalence of Posttraumatic Growth Hormone Deficiency Is Highly Dependent on the Diagnostic Set-up

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Klose, Marianne Christina; Stochholm, Kirstine; Janukonyté, Jourgita

2014-01-01

CONTEXT: Recent international guidelines suggest pituitary screening in patients with moderate and severe traumatic brain injury (TBI). Predominantly isolated GH deficiency (GHD) was reported in the literature, raising the question of potential methodological bias. OBJECTIVE: Our objective was to...

The GH/IGF-1 axis in obesity: pathophysiology and therapeutic considerations.

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Berryman, Darlene E; Glad, Camilla A M; List, Edward O; Johannsson, Gudmundur

2013-06-01

Obesity has become one of the most common medical problems in developed countries, and this disorder is associated with high incidences of hypertension, dyslipidaemia, cardiovascular disease, type 2 diabetes mellitus and specific cancers. Growth hormone (GH) stimulates the production of insulin-like growth factor 1 in most tissues, and together GH and insulin-like growth factor 1 exert powerful collective actions on fat, protein and glucose metabolism. Clinical trials assessing the effects of GH treatment in patients with obesity have shown consistent reductions in total adipose tissue mass, in particular abdominal and visceral adipose tissue depots. Moreover, studies in patients with abdominal obesity demonstrate a marked effect of GH therapy on body composition and on lipid and glucose homeostasis. Therefore, administration of recombinant human GH or activation of endogenous GH production has great potential to influence the onset and metabolic consequences of obesity. However, the clinical use of GH is not without controversy, given conflicting results regarding its effects on glucose metabolism. This Review provides an introduction to the role of GH in obesity and summarizes clinical and preclinical data that describe how GH can influence the obese state.

Metabolic impact of adult-onset, isolated, growth hormone deficiency (AOiGHD due to destruction of pituitary somatotropes.

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Raul M Luque

2011-01-01

Full Text Available Growth hormone (GH inhibits fat accumulation and promotes protein accretion, therefore the fall in GH observed with weight gain and normal aging may contribute to metabolic dysfunction. To directly test this hypothesis a novel mouse model of adult onset-isolated GH deficiency (AOiGHD was generated by cross breeding rat GH promoter-driven Cre recombinase mice (Cre with inducible diphtheria toxin receptor mice (iDTR and treating adult Cre(+/-,iDTR(+/- offspring with DT to selectively destroy the somatotrope population of the anterior pituitary gland, leading to a reduction in circulating GH and IGF-I levels. DT-treated Cre(-/-,iDTR(+/- mice were used as GH-intact controls. AOiGHD improved whole body insulin sensitivity in both low-fat and high-fat fed mice. Consistent with improved insulin sensitivity, indirect calorimetry revealed AOiGHD mice preferentially utilized carbohydrates for energy metabolism, as compared to GH-intact controls. In high-fat, but not low-fat fed AOiGHD mice, fat mass increased, hepatic lipids decreased and glucose clearance and insulin output were impaired. These results suggest the age-related decline in GH helps to preserve systemic insulin sensitivity, and in the context of moderate caloric intake, prevents the deterioration in metabolic function. However, in the context of excess caloric intake, low GH leads to impaired insulin output, and thereby could contribute to the development of diabetes.

Endurance training and GH administration in elderly women

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Lange, K H; Lorentsen, J; Isaksson, F

2001-01-01

and after completion of the training program. Similarly, no effect on subcutaneous abdominal adipose tissue lipolysis was observed when combining endurance training with rhGH administration. However, in both the placebo and the GH groups, fat oxidation was significantly increased during exercise performed......In the present study, the effect of endurance training alone and endurance training combined with recombinant human growth hormone (rhGH) administration on subcutaneous abdominal adipose tissue lipolysis was investigated. Sixteen healthy women [age 75 +/- 2 yr (mean +/- SE)] underwent a 12-wk...... endurance training program on a cycle ergometer. rhGH was administered in a randomized, double-blinded, placebo-controlled design in addition to the training program. Subcutaneous abdominal adipose tissue lipolysis was estimated by means of microdialysis combined with measurements of subcutaneous abdominal...

Differential effects on kidney and liver growth of a non-viral hGH-expression vector in hypophysectomized mice

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Khamaisi, Mogher; Søndergaard, Morten; Segev, Yael

2007-01-01

Non-viral gene transfer was investigated as a potential modality for the treatment of growth hormone deficiency (GHD) using hypophysectomized (Hx) mice as a model. Hx mice were injected with a control plasmid or a plasmid containing the human (h) GH gene driven by a ubiquitin promoter, or left...... and serum IGF-I levels, has differential effects on renal growth and glomerular volume. The potential effects of such excess glomerular growth induced by this intervention require further investigation....

Genome-wide identification of CBL family and expression analysis of CBLs in response to potassium deficiency in cotton

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Tingting Lu

2017-08-01

Full Text Available Calcineurin B-like (CBL proteins, as calcium sensors, play pivotal roles in plant responses to diverse abiotic stresses and in growth and development through interaction with CBL-interacting protein kinases (CIPKs. However, knowledge about functions and evolution of CBLs in Gossypium plants is scarce. Here, we conducted a genome-wide survey and identified 13, 13 and 22 CBL genes in the progenitor diploid Gossypium arboreum and Gossypium raimondii, and the cultivated allotetraploid Gossypium hirsutum, respectively. Analysis of physical properties, chromosomal locations, conserved domains and phylogeny indicated rather conserved nature of CBLs among the three Gossypium species. Moreover, these CBLs have closer genetic evolutionary relationship with the CBLs from cocoa than with those from other plants. Most CBL genes underwent evolution under purifying selection in the three Gossypium plants. Additionally, nearly all G. hirsutum CBL (GhCBL genes were expressed in the root, stem, leaf, flower and fiber. Many GhCBLs were preferentially expressed in the flower while several GhCBLs were mainly expressed in roots. Expression patterns of GhCBL genes in response to potassium deficiency were also studied. The expression of most GhCBLs were moderately induced in roots after treatments with low-potassium stress. Yeast two-hybrid experiments indicated that GhCBL1-2, GhCBL1-3, GhCBL4-4, GhCBL8, GhCBL9 and GhCBL10-3 interacted with GhCIPK23, respectively. Our results provided a comprehensive view of the CBLs and valuable information for researchers to further investigate the roles and functional mechanisms of the CBLs in Gossypium.

pKa modulation of the acid/base catalyst within GH32 and GH68: a role in substrate/inhibitor specificity?

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Shuguang Yuan

Full Text Available Glycoside hydrolases of families 32 (GH32 and 68 (GH68 belong to clan GH-J, containing hydrolytic enzymes (sucrose/fructans as donor substrates and fructosyltransferases (sucrose/fructans as donor and acceptor substrates. In GH32 members, some of the sugar substrates can also function as inhibitors, this regulatory aspect further adding to the complexity in enzyme functionalities within this family. Although 3D structural information becomes increasingly available within this clan and huge progress has been made on structure-function relationships, it is not clear why some sugars bind as inhibitors without being catalyzed. Conserved aspartate and glutamate residues are well known to act as nucleophile and acid/bases within this clan. Based on the available 3D structures of enzymes and enzyme-ligand complexes as well as docking simulations, we calculated the pKa of the acid-base before and after substrate binding. The obtained results strongly suggest that most GH-J members show an acid-base catalyst that is not sufficiently protonated before ligand entrance, while the acid-base can be fully protonated when a substrate, but not an inhibitor, enters the catalytic pocket. This provides a new mechanistic insight aiming at understanding the complex substrate and inhibitor specificities observed within the GH-J clan. Moreover, besides the effect of substrate entrance on its own, we strongly suggest that a highly conserved arginine residue (in the RDP motif rather than the previously proposed Tyr motif (not conserved provides the proton to increase the pKa of the acid-base catalyst.

Genetic and biochemical characterization of the GH72 family of cell wall transglycosylases in Neurospora crassa.

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Ao, Jie; Free, Stephen J

2017-04-01

The Neurospora crassa genome encodes five GH72 family transglycosylases, and four of these enzymes (GEL-1, GEL-2, GEL-3 and GEL-5) have been found to be present in the cell wall proteome. We carried out an extensive genetic analysis on the role of these four transglycosylases in cell wall biogenesis and demonstrated that the transglycosylases are required for the formation of a normal cell wall. As suggested by the proteomic analysis, we found that multiple transglycosylases were being expressed in N. crassa cells and that different combinations of the enzymes are required in different cell types. The combination of GEL-1, GEL-2 and GEL-5 is required for the growth of vegetative hyphae, while the GEL-1, GEL-2, GEL-3 combination is needed for the production of aerial hyphae and conidia. Our data demonstrates that the enzymes are redundant with partially overlapping enzymatic activities, which provides the fungus with a robust cell wall biosynthetic system. Characterization of the transglycosylase-deficient mutants demonstrated that the incorporation of cell wall proteins was severely compromised. Interestingly, we found that the transglycosylase-deficient mutant cell walls contained more β-1,3-glucan than the wild type cell wall. Our results demonstrate that the GH72 transglycosylases are not needed for the incorporation of β-1,3-glucan into the cell wall, but they are required for the incorporation of cell wall glycoprotein into the cell wall. Copyright © 2017 Elsevier Inc. All rights reserved.

[A case of GH and TSH secreting pituitary macroadenoma].

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Gołkowski, Filip; Buziak-Bereza, Monika; Stefańska, Agnieszka; Trofimiuk, Małgorzata; Pantofliński, Jacek; Huszno, Bohdan; Czepko, Ryszard; Adamek, Dariusz

2006-01-01

A case of GH and TSH secreting pituitary macroadenoma is reported. A 45-year-old female presented clinical features of acromegaly (the abnormal growth of the hands and feet, with lower jaw protrusion), diabetes mellitus, hypertension, nodular goiter and hyperthyroidism of unclear origin. NMR pituitary imaging revealed intra and extrasellar tumor. The laboratory examinations showed very high plasma levels of GH and IGF-1 and normal level of TSH coexisting with high plasma levels of free thyroid hormones. Pharmacological pretreatment with somatostatin analogues caused the substantial reduction of GH and TSH plasma levels. Histological and immunohistochemical examination of the tissue obtained at transsphenoidal surgery showed GH and TSH secreting adenoma. The laboratory examinations after surgery showed normal GH and IGF-1 plasma levels and reduced insulin requirement, what indicates radical operation. The very low plasma levels of TSH and free thyroid hormones after surgery and immunohistochemical examination suggest central hyperthyroidism due to TSH secreting pituitary tumor (thyrotropinoma).

Growth hormone (GH)-independent dimerization of GH receptor by a leucine zipper results in constitutive activation

DEFF Research Database (Denmark)

Behncken, S N; Billestrup, Nils; Brown, R

2000-01-01

Growth hormone initiates signaling by inducing homodimerization of two GH receptors. Here, we have sought to determine whether constitutively active receptor can be created in the absence of the extracellular domain by substituting it with high affinity leucine zippers to create dimers of the gro......Growth hormone initiates signaling by inducing homodimerization of two GH receptors. Here, we have sought to determine whether constitutively active receptor can be created in the absence of the extracellular domain by substituting it with high affinity leucine zippers to create dimers...

Detection of GH abuse in sport: Past, present and future.

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Barroso, Osquel; Schamasch, Patrick; Rabin, Olivier

2009-08-01

Due to its considered performance enhancing effects, human growth hormone (hGH) is abused as a doping agent in sport. Its misuse also carries potentially serious side effects to a person's health. Consequently, hGH and its releasing factors are prohibited in sport, as established in the Prohibited List which is updated and published yearly by the World Anti-Doping Agency (WADA). In order to fight the menace that hGH doping poses to the spirit of sport and to the health of athletes, the sport movement and the anti-doping authorities, initially led by the International Olympic Committee (IOC) and later by WADA, have put substantial efforts into developing tests for its detection. Currently, a primary analytical approach, the isoform differential immunoassay, has been implemented in WADA-accredited laboratories. In parallel, a second, indirect approach for the detection of hGH abuse, based on the quantification of hGH-associated biological markers, has been developed. The final aim is to combine both methodologies to improve the sensitivity and expand the time window to detect doping with hGH. In addition, novel analytical procedures, based on proteomic and genomic technologies as well as the use of mass spectrometry-based methods of detection, are being investigated for future application in hGH anti-doping tests.

Environmental stresses of field growth allow cinnamyl alcohol dehydrogenase-deficient Nicotiana attenuata plants to compensate for their structural deficiencies.

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Kaur, Harleen; Shaker, Kamel; Heinzel, Nicolas; Ralph, John; Gális, Ivan; Baldwin, Ian T

2012-08-01

The organized lignocellulosic assemblies of cell walls provide the structural integrity required for the large statures of terrestrial plants. Silencing two CINNAMYL ALCOHOL DEHYDROGENASE (CAD) genes in Nicotiana attenuata produced plants (ir-CAD) with thin, red-pigmented stems, low CAD and sinapyl alcohol dehydrogenase activity, low lignin contents, and rubbery, structurally unstable stems when grown in the glasshouse (GH). However, when planted into their native desert habitat, ir-CAD plants produced robust stems that survived wind storms as well as the wild-type plants. Despite efficient silencing of NaCAD transcripts and enzymatic activity, field-grown ir-CAD plants had delayed and restricted spread of red stem pigmentation, a color change reflecting blocked lignification by CAD silencing, and attained wild-type-comparable total lignin contents. The rubbery GH phenotype was largely restored when field-grown ir-CAD plants were protected from wind, herbivore attack, and ultraviolet B exposure and grown in restricted rooting volumes; conversely, it was lost when ir-CAD plants were experimentally exposed to wind, ultraviolet B, and grown in large pots in growth chambers. Transcript and liquid chromatography-electrospray ionization-time-of-flight analysis revealed that these environmental stresses enhanced the accumulation of various phenylpropanoids in stems of field-grown plants; gas chromatography-mass spectrometry and nuclear magnetic resonance analysis revealed that the lignin of field-grown ir-CAD plants had GH-grown comparable levels of sinapaldehyde and syringaldehyde cross-linked into their lignins. Additionally, field-grown ir-CAD plants had short, thick stems with normal xylem element traits, which collectively enabled field-grown ir-CAD plants to compensate for the structural deficiencies associated with CAD silencing. Environmental stresses play an essential role in regulating lignin biosynthesis in lignin-deficient plants.

The Cytoplasmic Tail Domain of Epstein-Barr Virus gH Regulates Membrane Fusion Activity through Altering gH Binding to gp42 and Epithelial Cell Attachment

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Jia Chen

2016-11-01

Full Text Available Epstein-Barr virus (EBV is associated with infectious mononucleosis and a variety of cancers as well as lymphoproliferative disorders in immunocompromised patients. EBV mediates viral entry into epithelial and B cells using fusion machinery composed of four glycoproteins: gB, the gH/gL complex, and gp42. gB and gH/gL are required for both epithelial and B cell fusion. The specific role of gH/gL in fusion has been the most elusive among the required herpesvirus entry glycoproteins. Previous mutational studies have focused on the ectodomain of EBV gH and not on the gH cytoplasmic tail domain (CTD. In this study, we chose to examine the function of the gH CTD by making serial gH truncation mutants as well as amino acid substitution mutants to determine the importance of the gH CTD in epithelial and B cell fusion. Truncation of 8 amino acids (aa 698 to 706 of the gH CTD resulted in diminished fusion activity using a virus-free syncytium formation assay and fusion assay. The importance of the amino acid composition of the gH CTD was also investigated by amino acid substitutions that altered the hydrophobicity or hydrophilicity of the CTD. These mutations also resulted in diminished fusion activity. Interestingly, some of the gH CTD truncation mutants and hydrophilic tail substitution mutants lost the ability to bind to gp42 and epithelial cells. In summary, our studies indicate that the gH CTD is an important functional domain.

The Impact of Growth Hormone Therapy on the Apoptosis Assessment in CD34+ Hematopoietic Cells from Children with Growth Hormone Deficiency

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Miłosz Piotr Kawa

2017-01-01

Full Text Available Growth hormone (GH modulates hematopoietic cell homeostasis and is associated with apoptosis control, but with limited mechanistic insights. Aim of the study was to determine whether GH therapeutic supplementation (GH-TS could affect apoptosis of CD34+ cells enriched in hematopoietic progenitor cells of GH deficient (GHD children. CD34+ cells from peripheral blood of 40 GHD children were collected before and in 3rd and 6th month of GH-TS and compared to 60 controls adjusted for bone age, sex, and pubertal development. Next, apoptosis assessment via different molecular techniques was performed. Finally, to comprehensively characterize apoptosis process, global gene expression profile was determined using genome-wide RNA microarray technology. Results showed that GH-TS significantly reduced spontaneous apoptosis in CD34+ cells (p < 0.01 and results obtained using different methods to detect early and late apoptosis in analyzed cells population were consistent. GH-TS was also associated with significant downregulation of several members of TNF-alpha superfamily and other genes associated with apoptosis and stress response. Moreover, the significant overexpression of cyto-protective and cell cycle-associated genes was detected. These findings suggest that recombinant human GH has a direct anti-apoptotic activity in hematopoietic CD34+ cells derived from GHD subjects in course of GH-TS.

Structure and kinetic investigation of Streptococcus pyogenes family GH38 alpha-mannosidase.

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Michael D L Suits

2010-02-01

Full Text Available The enzymatic hydrolysis of alpha-mannosides is catalyzed by glycoside hydrolases (GH, termed alpha-mannosidases. These enzymes are found in different GH sequence-based families. Considerable research has probed the role of higher eukaryotic "GH38" alpha-mannosides that play a key role in the modification and diversification of hybrid N-glycans; processes with strong cellular links to cancer and autoimmune disease. The most extensively studied of these enzymes is the Drosophila GH38 alpha-mannosidase II, which has been shown to be a retaining alpha-mannosidase that targets both alpha-1,3 and alpha-1,6 mannosyl linkages, an activity that enables the enzyme to process GlcNAc(Man(5(GlcNAc(2 hybrid N-glycans to GlcNAc(Man(3(GlcNAc(2. Far less well understood is the observation that many bacterial species, predominantly but not exclusively pathogens and symbionts, also possess putative GH38 alpha-mannosidases whose activity and specificity is unknown.Here we show that the Streptococcus pyogenes (M1 GAS SF370 GH38 enzyme (Spy1604; hereafter SpGH38 is an alpha-mannosidase with specificity for alpha-1,3 mannosidic linkages. The 3D X-ray structure of SpGH38, obtained in native form at 1.9 A resolution and in complex with the inhibitor swainsonine (K(i 18 microM at 2.6 A, reveals a canonical GH38 five-domain structure in which the catalytic "-1" subsite shows high similarity with the Drosophila enzyme, including the catalytic Zn(2+ ion. In contrast, the "leaving group" subsites of SpGH38 display considerable differences to the higher eukaryotic GH38s; features that contribute to their apparent specificity.Although the in vivo function of this streptococcal GH38 alpha-mannosidase remains unknown, it is shown to be an alpha-mannosidase active on N-glycans. SpGH38 lies on an operon that also contains the GH84 hexosaminidase (Spy1600 and an additional putative glycosidase. The activity of SpGH38, together with its genomic context, strongly hints at a function

Structural-Functional Analysis Reveals a Specific Domain Organization in Family GH20 Hexosaminidases.

Science.gov (United States)

Val-Cid, Cristina; Biarnés, Xevi; Faijes, Magda; Planas, Antoni

2015-01-01

Hexosaminidases are involved in important biological processes catalyzing the hydrolysis of N-acetyl-hexosaminyl residues in glycosaminoglycans and glycoconjugates. The GH20 enzymes present diverse domain organizations for which we propose two minimal model architectures: Model A containing at least a non-catalytic GH20b domain and the catalytic one (GH20) always accompanied with an extra α-helix (GH20b-GH20-α), and Model B with only the catalytic GH20 domain. The large Bifidobacterium bifidum lacto-N-biosidase was used as a model protein to evaluate the minimal functional unit due to its interest and structural complexity. By expressing different truncated forms of this enzyme, we show that Model A architectures cannot be reduced to Model B. In particular, there are two structural requirements general to GH20 enzymes with Model A architecture. First, the non-catalytic domain GH20b at the N-terminus of the catalytic GH20 domain is required for expression and seems to stabilize it. Second, the substrate-binding cavity at the GH20 domain always involves a remote element provided by a long loop from the catalytic domain itself or, when this loop is short, by an element from another domain of the multidomain structure or from the dimeric partner. Particularly, the lacto-N-biosidase requires GH20b and the lectin-like domain at the N- and C-termini of the catalytic GH20 domain to be fully soluble and functional. The lectin domain provides this remote element to the active site. We demonstrate restoration of activity of the inactive GH20b-GH20-α construct (model A architecture) by a complementation assay with the lectin-like domain. The engineering of minimal functional units of multidomain GH20 enzymes must consider these structural requirements.

Effects of short-term glucocorticoid deprivation on growth hormone (GH) response to GH-releasing peptide-6: Studies in normal men and in patients with adrenal insufficiency

OpenAIRE

Pinto, Ana Claudia de Assis Rocha [UNIFESP; Dias-da-Silva, Magnus Régios [UNIFESP; Martins, Manoel R. [UNIFESP; Brunner, Elisa [UNIFESP; Lengyel, Ana Maria Judith [UNIFESP

2000-01-01

There are no data in the literature about the effects of glucocorticoid deprivation on GH-releasing peptide-g (GHRP-6)-induced GH release. the aims of this study were to evaluate GH responsiveness to GHRP-6 1) after metyrapone administration in normal men, and 2) in patients with chronic hypocortisolism after glucocorticoid withdrawal for 72 h. in normal subjects, metyrapone ingestion did not alter significantly GH responsiveness to GHRP-6 [n = 8; peak, 39.3 +/- 7.1 mu g/L; area under the cur...

GH mediates exercise-dependent activation of SVZ neural precursor cells in aged mice.

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Daniel G Blackmore

Full Text Available Here we demonstrate, both in vivo and in vitro, that growth hormone (GH mediates precursor cell activation in the subventricular zone (SVZ of the aged (12-month-old brain following exercise, and that GH signaling stimulates precursor activation to a similar extent to exercise. Our results reveal that both addition of GH in culture and direct intracerebroventricular infusion of GH stimulate neural precursor cells in the aged brain. In contrast, no increase in neurosphere numbers was observed in GH receptor null animals following exercise. Continuous infusion of a GH antagonist into the lateral ventricle of wild-type animals completely abolished the exercise-induced increase in neural precursor cell number. Given that the aged brain does not recover well after injury, we investigated the direct effect of exercise and GH on neural precursor cell activation following irradiation. This revealed that physical exercise as well as infusion of GH promoted repopulation of neural precursor cells in irradiated aged animals. Conversely, infusion of a GH antagonist during exercise prevented recovery of precursor cells in the SVZ following irradiation.

GH Mediates Exercise-Dependent Activation of SVZ Neural Precursor Cells in Aged Mice

Science.gov (United States)

Blackmore, Daniel G.; Vukovic, Jana; Waters, Michael J.; Bartlett, Perry F.

2012-01-01

Here we demonstrate, both in vivo and in vitro, that growth hormone (GH) mediates precursor cell activation in the subventricular zone (SVZ) of the aged (12-month-old) brain following exercise, and that GH signaling stimulates precursor activation to a similar extent to exercise. Our results reveal that both addition of GH in culture and direct intracerebroventricular infusion of GH stimulate neural precursor cells in the aged brain. In contrast, no increase in neurosphere numbers was observed in GH receptor null animals following exercise. Continuous infusion of a GH antagonist into the lateral ventricle of wild-type animals completely abolished the exercise-induced increase in neural precursor cell number. Given that the aged brain does not recover well after injury, we investigated the direct effect of exercise and GH on neural precursor cell activation following irradiation. This revealed that physical exercise as well as infusion of GH promoted repopulation of neural precursor cells in irradiated aged animals. Conversely, infusion of a GH antagonist during exercise prevented recovery of precursor cells in the SVZ following irradiation. PMID:23209615

Transcription elongation factors are involved in programming hormone production in pituitary neuroendocrine GH4C1 cells.

Science.gov (United States)

Fujita, Toshitsugu; Piuz, Isabelle; Schlegel, Werner

2010-05-05

Transcription elongation of many eukaryotic genes is regulated. Two negative transcription elongation factors, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) sensitivity-inducing factor (DSIF) and negative elongation factor (NELF) are known to stall collaboratively RNA polymerase II promoter proximally. We discovered that DSIF and NELF are linked to hormone expression in rat pituitary GH4C1 cells. When NELF-E, a subunit of NELF or Spt5, a subunit of DSIF was stably knocked-down, prolactin (PRL) expression was increased both at the mRNA and protein levels. In contrast, stable knock-down of only Spt5 abolished growth hormone (GH) expression. Transient NELF-E knock-down increased coincidentally PRL expression and enhanced transcription of a PRL-promoter reporter gene. However, no direct interaction of NELF with the PRL gene could be demonstrated by chromatin immuno-precipitation. Thus, NELF suppressed PRL promoter activity indirectly. In conclusion, transcription regulation by NELF and DSIF is continuously involved in the control of hormone production and may contribute to neuroendocrine cell differentiation. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Molecular genetics of growth hormone deficient children: correlation with auxology and response to first year of growth hormone therapy.

Science.gov (United States)

Khadilkar, Vaman; Phadke, Nikhil; Khatod, Kavita; Ekbote, Veena; Gupte, Supriya Phanse; Nadar, Ruchi; Khadilkar, Anuradha

2017-05-24

With the paucity of available literature correlating genetic mutation and response to treatment, we aimed to study the genetic makeup of children with growth hormone (GH) deficiency in Western India and correlate the mutation with auxology and response to GH treatment at end of 1 year. Fifty-three (31 boys and 22 girls) children with severe short stature (height for age z-score imaging (MRI) brain scan was done in all. Genetic mutations were tested for in GH1, GHRH, LHX3, LHX4 and PROP1, POU1F1 and HESX1 genes. Mean age at presentation was 9.7±5.1 years. Thirty-seven children (Group A) had no genetic mutation detected. Six children (Group B) had mutations in the GH releasing hormone receptor (GHRHR) gene, while eight children (Group C) had mutation in the GH1 gene. In two children, one each had a mutation in PROP1 and LHX3. There was no statistically significant difference in baseline height, weight and BMI for age z-score and height velocity for age z-score (HVZ). HVZ was significantly lower, post 1 year GH treatment in the group with homozygous GH1 deletion than in children with no genetic defect. Response to GH at the end of 1 year was poor in children with the homozygous GH1 deletion as compared to those with GHRHR mutation or without a known mutation.

EFFECT OF GROWTH HORMONE REPLACEMENT THERAPY ON THE QUALITY OF LIFE IN WOMEN WITH GROWTH HORMONE DEFICIENCY WHO HAVE A HISTORY OF ACROMEGALY VERSUS OTHER DISORDERS

Science.gov (United States)

Valassi, Elena; Brick, Danielle J.; Johnson, Jessica C.; Biller, Beverly M. K.; Klibanski, Anne; Miller, Karen K.

2013-01-01

Objective To compare the response in quality of life (QoL) to growth hormone (GH) replacement in women with GH deficiency (GHD) and a history of acromegaly with that in women with GHD of other causes. Methods Fifty-five women with GHD were studied: 17 with prior acromegaly and 38 with other causes of GHD. We compared two 6-month, randomized, placebo-controlled studies of GH therapy in women with hypopituitarism conducted with use of the same design—one in women with a history of acromegaly and one in women with no prior acromegaly. QoL was assessed with the following questionnaires: the QoL-Assessment of Growth Hormone deficiency in Adults (AGHDA), the Symptom Questionnaire, and the 36-Item Short-Form Health Survey (SF-36). Results The 2 groups had comparable mean pretreatment age, body mass index, and QoL scores and comparable mean GH dose at 6 months (0.61 ± 0.30 versus 0.67 ± 0.27 mg daily). After 6 months of GH replacement therapy, women with GHD and prior acromegaly demonstrated a greater improvement in AGHDA score, four SF-36 subscales (Role Limitations due to Physical Health, Energy or Fatigue, Emotional Well-Being, and Social Functioning), and the Somatic Symptoms subscale of the Symptom Questionnaire than did women with GHD of other causes. Poorer pretreatment QoL was associated with a greater improvement in QoL after administration of GH. Conclusion In this study, GH replacement therapy improved QoL in women with GHD and a history of acromegaly but not in women with GHD due to other hypothalamic and pituitary disorders. Further studies are needed to determine the long-term risks versus benefits of GH replacement in patients who develop GHD after definitive treatment for acromegaly. PMID:22440981

New insights into the mechanism and actions of growth hormone (GH) in poultry.

Science.gov (United States)

Vasilatos-Younken, R; Wang, X H; Zhou, Y; Day, J R; McMurtry, J P; Rosebrough, R W; Decuypere, E; Buys, N; Darras, V; Beard, J L; Tomas, F

1999-10-01

Despite well documented anabolic effects of GH in mammals, a clear demonstration of such responses in domestic poultry is lacking. Recently, comprehensive dose-response studies of GH have been conducted in broilers during late post-hatch development (8 to 9 weeks of age). GH reduced feed intake (FI) and body weight gain in a dose-dependent manner, whereas birds pair-fed to the level of voluntary FI of GH-infused birds did not differ from controls. The reduction in voluntary FI may involve centrally mediated mechanisms, as hypothalamic neuropeptide Y protein and mRNA were reduced with GH, coincident with the maximal depression in FI. Growth of breast muscle was also reduced in a dose-dependent manner. Circulating IGF-I was not enhanced by GH, despite evidence that early events in the GH signaling pathway were intact. A GH dose-dependent increase in circulating 3,3',5-triiodothyronine(T3) paralleled decreases in hepatic 5D-III monodeiodinase activity, whereas 5'D-I activity was not altered. This confirms that a marked hyperthyroid response to GH occurs in late posthatch chickens, resulting from a decrease in the degradative pathway of T3 metabolism. This secondary hyperthyroidism would account for the decreased skeletal muscle mass (52) and lack of enhanced IGF-I (53) in GH-treated birds. Based upon these studies, it is now evident that GH does in fact have significant effects in poultry, but metabolic responses may confound the anabolic potential of the hormone.

Increased fibrosis: A novel means by which GH influences white adipose tissue function.

Science.gov (United States)

Householder, Lara A; Comisford, Ross; Duran-Ortiz, Silvana; Lee, Kevin; Troike, Katie; Wilson, Cody; Jara, Adam; Harberson, Mitchell; List, Edward O; Kopchick, John J; Berryman, Darlene E

2018-04-01

White adipose tissue (WAT) fibrosis - the buildup of extracellular matrix (ECM) proteins, primarily collagen - is now a recognized hallmark of tissue dysfunction and is increased with obesity and lipodystrophy. While growth hormone (GH) is known to increase collagen in several tissues, no previous research has addressed its effect on ECM in WAT. Thus, the purpose of this study is to determine if GH influences WAT fibrosis. This study examined WAT from four distinct strains of GH-altered mice (bGH and GHA transgenic mice as well as two tissue specific GH receptor gene disrupted lines, fat growth hormone receptor knockout or FaGHRKO and liver growth hormone receptor knockout or LiGHRKO mice). Collagen content and adipocyte size were studied in all cohorts and compared to littermate controls. In addition, mRNA expression of fibrosis-associated genes was assessed in one cohort (6month old male bovine GH transgenic and WT mice) and cultured 3T3-L1 adipocytes treated with GH. Collagen stained area was increased in WAT from bGH mice, was depot-dependent, and increased with age. Furthermore, increased collagen content was associated with decreased adipocyte size in all depots but more dramatic changes in the subcutaneous fat pad. Notably, the increase in collagen was not associated with an increase in collagen gene expression or other genes known to promote fibrosis in WAT, but collagen gene expression was increased with acute GH administration in 3T3-LI cells. In contrast, evaluation of 6month old GH antagonist (GHA) male mice showed significantly decreased collagen in the subcutaneous depot. Lastly, to assess if GH induced collagen deposition directly or indirectly (via IGF-1), fat (Fa) and liver (Li) specific GHRKO mice were evaluated. Decreased fibrosis in FaGHRKO and increased fibrosis in LiGHRKO mice suggest GH is primarily responsible for the alterations in collagen. Our results show that GH action is positively associated with an increase in WAT collagen content as

Alström syndrome is associated with short stature and reduced GH reserve.

Science.gov (United States)

Romano, S; Maffei, P; Bettini, V; Milan, G; Favaretto, F; Gardiman, M; Marshall, J D; Greggio, N A; Pozzan, G B; Collin, G B; Naggert, J K; Bronson, R; Vettor, R

2013-10-01

Alström syndrome (ALMS) is a rare autosomal recessive monogenic disease included in an emerging class of genetic disorders called 'ciliopathies' and is likely to impact the central nervous system as well as metabolic and endocrine function. Individuals with ALMS present clinical features resembling a growth hormone deficiency (GHD) condition, but thus far no study has specifically investigated this aspect in a large population. Twenty-three patients with ALMS (age, 1-52 years; 11 males, 12 females) were evaluated for anthropometric parameters (growth charts and standard deviation score (SDS) of height, weight, BMI), GH secretion by growth hormone-releasing hormone + arginine test (GHRH-arg), bone age, and hypothalamic-pituitary magnetic resonance imaging (MRI). A group of 17 healthy subjects served as controls in the GH secretion study. Longitudinal retrospective and prospective data were utilized. The length-for-age measurements from birth to 36 months showed normal growth with most values falling within -0·67 SDS to +1·28 SDS. A progressive decrease in stature-for-age was observed after 10 years of age, with a low final height in almost all ALMS subjects (>16-20 years; mean SDS, -2·22 ± 1·16). The subset of 12 patients with ALMS tested for GHRH-arg showed a significantly shorter stature than age-matched controls (154·7 ± 10·6 cm vs 162·9 ± 4·8 cm, P = 0·009) and a mild increase in BMI (Kg/m(2) ) (27·8 ± 4·8 vs 24·1 ± 2·5, P = 0·007). Peak GH after GHRH-arg was significantly lower in patients with ALMS in comparison with controls (11·9 ± 6·9 μg/l vs 86·1 ± 33·2 μg/l, P short stature reported in ALMS may be at least partially influenced by impairment of GH secretion. © 2013 John Wiley & Sons Ltd.

Short stature and growth hormone deficiency in a girl with encephalocraniocutaneous lipomatosis and Jaffe-Campanacci syndrome: a case report

Directory of Open Access Journals (Sweden)

Eun mi Choi

2016-12-01

Full Text Available A 9-year-old Tajikistani girl presented to Keimyung University Dongsan Medical Center for evaluation of a skin lesion on her left eyelid, focal alopecia, unilateral ventricular dilatation, and aortic coarctation. She was diagnosed with encephalocraniocutaneous lipomatosis (ECCL according to Moog's diagnostic criteria. Café-au-lait spots were found on the left side of her trunk. Multiple nonossifying fibromas were found on her left proximal humerus, left distal femur, both proximal tibias, and left proximal fibula, suggesting Jaffe-Campanacci syndrome (JCS, following imaging of the extremities. Many JCS cases with multiple Café-au-lait macules, multiple nonossifying fibromas may actually have Neurofibromatosis type-1 (NF1. Thus, comprehensive molecular analysis to exclude NF1 mutation was performed using her blood sample. The NF1 mutation was not found. Her height was under the 3rd percentile and her bone age was delayed as compared with her chronological age. Baseline growth hormone (GH level was below the normal range. Using the insulin stimulation and levo-dihydroxyphenylalanine tests, GH deficiency was confirmed. We present a case of GH deficiency with typical features of ECCL and JCS.

Short stature and growth hormone deficiency in a girl with encephalocraniocutaneous lipomatosis and Jaffe-Campanacci syndrome: a case report.

Science.gov (United States)

Choi, Eun Mi; Jung, Nani; Shim, Ye Jee; Choi, Hee Joung; Kim, Joon Sik; Kim, Heung Sik; Song, Kwang Soon; Lee, Hee Jung; Kim, Sang Pyo

2016-12-01

A 9-year-old Tajikistani girl presented to Keimyung University Dongsan Medical Center for evaluation of a skin lesion on her left eyelid, focal alopecia, unilateral ventricular dilatation, and aortic coarctation. She was diagnosed with encephalocraniocutaneous lipomatosis (ECCL) according to Moog's diagnostic criteria. Café-au-lait spots were found on the left side of her trunk. Multiple nonossifying fibromas were found on her left proximal humerus, left distal femur, both proximal tibias, and left proximal fibula, suggesting Jaffe-Campanacci syndrome (JCS), following imaging of the extremities. Many JCS cases with multiple Café-au-lait macules, multiple nonossifying fibromas may actually have Neurofibromatosis type-1 (NF1). Thus, comprehensive molecular analysis to exclude NF1 mutation was performed using her blood sample. The NF1 mutation was not found. Her height was under the 3rd percentile and her bone age was delayed as compared with her chronological age. Baseline growth hormone (GH) level was below the normal range. Using the insulin stimulation and levo-dihydroxyphenylalanine tests, GH deficiency was confirmed. We present a case of GH deficiency with typical features of ECCL and JCS.

GH Travel & Mission Support System

Data.gov (United States)

US Agency for International Development — HTRAMS is a travel data collection system for GH that collects information on both the basic details of an employee's trips (destination, length, purpose, etc.) and...

Arginine Deficiency Causes Runting in the Suckling Period by Selectively Activating the Stress Kinase GCN2

NARCIS (Netherlands)

Marion, Vincent; Sankaranarayanan, Selvakumari; de Theije, Chiel; van Dijk, Paul; Lindsey, Patrick; Lamers, Marinus C.; Harding, Heather P.; Ron, David; Lamers, Wouter H.; Koehler, S. Eleonore

2011-01-01

Suckling "F/A2" mice, which overexpress arginase-I in their enterocytes, develop a syndrome (hypoargininemia, reduced hair and muscle growth, impaired B-cell maturation) that resembles IGF1 deficiency. The syndrome may result from an impaired function of the GH-IGF1 axis, activation of the

Effects of financial support on treatment of adolescents with growth hormone deficiency: a retrospective study in Japan.

Science.gov (United States)

Maeda, Eri; Higashi, Takahiro; Hasegawa, Tomonobu; Yokoya, Susumu; Mochizuki, Takahiro; Ishii, Tomohiro; Ito, Junko; Kanzaki, Susumu; Shimatsu, Akira; Takano, Koji; Tajima, Toshihiro; Tanaka, Hiroyuki; Tanahashi, Yusuke; Teramoto, Akira; Nagai, Toshiro; Hanew, Kunihiko; Horikawa, Reiko; Yorifuji, Toru; Wada, Naohiro; Tanaka, Toshiaki

2016-10-21

Treatment costs for children with growth hormone (GH) deficiency are subsidized by the government in Japan if the children meet clinical criteria, including height limits (boys: 156.4 cm; girls: 145.4 cm). However, several funding programs, such as a subsidy provided by local governments, can be used by those who exceed the height limits. In this study, we explored the impacts of financial support on GH treatment using this natural allocation. A retrospective analysis of 696 adolescent patients (451 boys and 245 girls) who reached the height limits was conducted. Associations between financial support and continuing treatment were assessed using multiple logistic regression analyses adjusting for age, sex, height, growth velocity, bone age, and adverse effects. Of the 696 children in the analysis, 108 (15.5 %) were still eligible for financial support. The proportion of children who continued GH treatment was higher among those who were eligible for support than among those who were not (75.9 % vs. 52.0 %, P financial support to continuing treatment were 4.04 (95 % confidence interval [CI]: 1.86-8.78) in boys and 1.72 (95 % CI: 0.80-3.70) in girls, after adjusting for demographic characteristics and clinical factors. Financial support affected decisions on treatment continuation for children with GH deficiency. Geographic variations in eligibility for financial support pose an ethical problem that needs policy attention. An appropriate balance between public spending on continuation of therapy and improved quality of life derived from it should be explored.

Environmental Stresses of Field Growth Allow Cinnamyl Alcohol Dehydrogenase-Deficient Nicotiana attenuata Plants to Compensate for their Structural Deficiencies1[C][W][OA

Science.gov (United States)

Kaur, Harleen; Shaker, Kamel; Heinzel, Nicolas; Ralph, John; Gális, Ivan; Baldwin, Ian T.

2012-01-01

The organized lignocellulosic assemblies of cell walls provide the structural integrity required for the large statures of terrestrial plants. Silencing two CINNAMYL ALCOHOL DEHYDROGENASE (CAD) genes in Nicotiana attenuata produced plants (ir-CAD) with thin, red-pigmented stems, low CAD and sinapyl alcohol dehydrogenase activity, low lignin contents, and rubbery, structurally unstable stems when grown in the glasshouse (GH). However, when planted into their native desert habitat, ir-CAD plants produced robust stems that survived wind storms as well as the wild-type plants. Despite efficient silencing of NaCAD transcripts and enzymatic activity, field-grown ir-CAD plants had delayed and restricted spread of red stem pigmentation, a color change reflecting blocked lignification by CAD silencing, and attained wild-type-comparable total lignin contents. The rubbery GH phenotype was largely restored when field-grown ir-CAD plants were protected from wind, herbivore attack, and ultraviolet B exposure and grown in restricted rooting volumes; conversely, it was lost when ir-CAD plants were experimentally exposed to wind, ultraviolet B, and grown in large pots in growth chambers. Transcript and liquid chromatography-electrospray ionization-time-of-flight analysis revealed that these environmental stresses enhanced the accumulation of various phenylpropanoids in stems of field-grown plants; gas chromatography-mass spectrometry and nuclear magnetic resonance analysis revealed that the lignin of field-grown ir-CAD plants had GH-grown comparable levels of sinapaldehyde and syringaldehyde cross-linked into their lignins. Additionally, field-grown ir-CAD plants had short, thick stems with normal xylem element traits, which collectively enabled field-grown ir-CAD plants to compensate for the structural deficiencies associated with CAD silencing. Environmental stresses play an essential role in regulating lignin biosynthesis in lignin-deficient plants. PMID:22645069

Expanding the spectrum of mutations in GH1 and GHRHR: genetic screening in a large cohort of patients with congenital isolated growth hormone deficiency

DEFF Research Database (Denmark)

Alatzoglou, Kyriaki S; Turton, James P; Kelberman, Daniel

2009-01-01

mutations in GH1 (C182X, G120V, R178H, IVS3+4nt, a>t) and GHRHR (W273S, R94L, R162W). Autosomal dominant, type II IGHD was the commonest form (52.4%), followed by type IB (42.8%) and type IA (4.8%). Patients with type II IGHD had highly variable phenotypes. There was no difference in the endocrinology...... or magnetic resonance imaging appearance between patients with and without mutations, although those with mutations presented with more significant growth failure (height, -4.7 +/- 1.6 SDS vs. -3.4 +/- 1.7 SDS) (P = 0.001). There was no apparent difference between patients with mutations in GH1 and GHRHR...

Continuous 24-hour intravenous infusion of recombinant human growth hormone (GH)-releasing hormone-(1-44)-amide augments pulsatile, entropic, and daily rhythmic GH secretion in postmenopausal women equally in the estrogen-withdrawn and estrogen-supplemented states.

Science.gov (United States)

Evans, W S; Anderson, S M; Hull, L T; Azimi, P P; Bowers, C Y; Veldhuis, J D

2001-02-01

How estrogen amplifies GH secretion in the human is not known. The present study tests the clinical hypothesis that estradiol modulates the stimulatory actions of a primary GH feedforward signal, GHRH. To this end, we investigated the ability of short-term (7- to 12-day) supplementation with oral estradiol vs. placebo to modulate basal, pulsatile, entropic, and 24-h rhythmic GH secretion driven by a continuous iv infusion of recombinant human GHRH-(1--44)-amide vs. saline in nine healthy postmenopausal women. Volunteers underwent concurrent blood sampling every 10 min for 24 h on four occasions in a prospectively randomized, single blind, within-subject cross-over design (placebo/saline, placebo/GHRH, estradiol/saline, estradiol/GHRH). Intensively sampled serum GH concentrations were quantitated by ultrasensitive chemiluminescence assay. Basal, pulsatile, entropic (feedback-sensitive), and 24-h rhythmic modes of GH secretion were appraised by deconvolution analysis, the approximate entropy (ApEn) statistic, and cosine regression, respectively. ANOVA revealed that continuous iv infusion of GHRH in the estrogen-withdrawn (control) milieu 1) amplified individual basal (P = 0.00011) and pulsatile (P < 10(-13)) GH secretion rates by 12- and 11-fold, respectively; 2) augmented GH secretory burst mass and amplitude each by 10-fold (P < 10(-11)), without altering GH secretory burst frequency, duration, or half-life; 3) increased the disorderliness (ApEn) of GH release patterns (P = 0.0000002); 4) elevated the mesor (cosine mean) and amplitude of the 24-h rhythm in serum GH concentrations by nearly 30-fold (both P < 10(-12)); 5) induced a phase advance in the clocktime of the GH zenith (P = 0.021); and 6) evoked a new 24-h rhythm in GH secretory burst mass with a maximum at 0018 h GH (P < 10(-3)), while damping the mesor of the 24-h rhythm in GH interpulse intervals (P < 0.025). Estradiol supplementation alone 1) increased the 24-h mean and integrated serum GH concentration

Nuclear power plant transients: where are we

International Nuclear Information System (INIS)

Majumdar, D.

1984-05-01

This document is in part a postconference review and summary of the American Nuclear Society sponsored Anticipated and Abnormal Plant Transients in Light Water Reactors Conference held in Jackson, Wyoming, September 26-29, 1983, and in part a reflection upon the issues of plant transients and their impact on the viability of nuclear power. This document discusses state-of-the-art knowledge, deficiencies, and future directions in the plant transients area as seen through this conference. It describes briefly what was reported in this conference, emphasizes areas where it is felt there is confidence in the nuclear industry, and also discusses where the experts did not have a consensus. Areas covered in the document include major issues in operational transients, transient management, transient events experience base, the status of the analytical tools and their capabilities, probabilistic risk assessment applications in operational transients, and human factors impact on plant transients management

Effects of 1-year growth hormone replacement therapy on thyroid volume and function of the children and adolescents with idiopathic growth hormone deficiency.

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Keskin, Meliksah; Bayramoglu, Elvan; Aycan, Zehra

2017-10-26

There are different opinions about the effects of growth hormone replacement therapy (GHRT) on thyroid function and volume. This study aimed to assess the effects of GHRT on thyroid volume and function in the children and adolescents with growth hormone (GH) deficiency. A total of 29 patients diagnosed with GH deficiency were enrolled in the study. The control group consisted of 29 cases matched for age, gender and pubertal period with the patients. Thyroid function tests and insulin-like growth factor levels were measured, simultaneously thyroid volumes were assessed by ultrasonography at the initiation period and at the end of GHRT. Thyroid volumes of the patient group was -0.55±1.1 standard deviations (SDs) initially; whereas at the end of 1 year it was found to be -0.29±1.29 SDs and both SDs of thyroid volumes did not differ significantly. The SDs of thyroid volume of the control group was -0.85±1.03 SDs initially and -0.72±0.85 SDs at the end of 1 year; and they did not differ significantly. On the other hand, after GHRT of 1 year, thyroid stimulating hormone (TSH) and free thyroxine (T4) levels decreased. It was observed that SDs of thyroid gland volumes did not change in GH deficient children and adolescents after GHRT.

Effects of Growth Hormone Replacement on Peripheral Muscle and Exercise Capacity in Severe Growth Hormone Deficiency

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Susana Gonzalez

2018-02-01

Full Text Available ObjectiveThe aim of this study is to evaluate the effect of growth hormone therapy (rGH on mitochondrial function on peripheral muscle and to correlate with exercise capacity in subjects with severe adult growth hormone deficiency (GHD.DesignSix months, double-blind, randomized, crossover, placebo-controlled trial of subcutaneous rGH in 17 patients with GHD.MeasurementsQuadriceps muscle biopsies were obtained at baseline, 3 months, and 6 months to measure succinate dehydrogenase (SDH to assess mitochondrial activity. Exercise capacity was measured with cardiopulmonary exercise testing. Lipids, glycemic parameters, and body fat levels were also measured.ResultsSerum insulin-like growth factor 1 (IGF1 levels reduced fat mass by 3.2% (p < 0.05 and normalized with rGH in the active phase (p < 0.005. Patients showed an increase in SDH (p < 0.01 from base line that differed between placebo and rGH therapy treatment groups (p < 0.05: those treated by rGH followed by placebo showed a significant increase in SDH (p < 0.001 followed by a decrease, with a significant between group difference at the end of 6 months (p < 0.05. No significant improvements or correlation with exercise capacity was found.ConclusionShort-term rGH for 3 months normalized IGF1 levels, reduced fat mass, and had a significant effect on mitochondrial function, but exercise capacity was unchanged.Clinical Trial RegistrationNumber ISRCTN94165486.

A case of functional growth hormone deficiency and early growth retardation in a child with IFT172 mutations.

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Lucas-Herald, Angela K; Kinning, Esther; Iida, Aritoshi; Wang, Zheng; Miyake, Noriko; Ikegawa, Shiro; McNeilly, Jane; Ahmed, S Faisal

2015-04-01

Ciliopathies are a group of rare conditions that present through a wide range of manifestations. Given the relative common occurrence of defects of the GH/IGF-I axis in children with short stature and growth retardation, the association between ciliopathies and these defects needs further attention. Our patient is a boy who was born at term and noted to have early growth retardation and weight gain within the first 18 months of life. Biochemical tests demonstrated low IGF-I but a normal peak GH on stimulation and an adequate increase in IGF-I on administration of recombinant human growth hormone (rhGH). A magnetic resonance imaging scan revealed pituitary hypoplasia and an ectopic posterior pituitary. His growth responded well to rhGH therapy. Subsequently he also developed a retinopathy of his rods and cones, metaphyseal dysplasia, and hypertension with renal failure requiring renal replacement therapy. Whole-exome sequencing demonstrated compound heterozygous mutations of IFT172, thus consistent with a ciliopathy. This is the first reported case of a child with a mutation in IFT172 who presented with growth retardation in early childhood and was initially managed as a case of functional GH deficiency that responded to rhGH therapy. This case highlights the importance of ciliary function in pituitary development and the link between early onset growth failure and ciliopathies.

Iodine deficiency and thyroid disorders.

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Zimmermann, Michael B; Boelaert, Kristien

2015-04-01

Iodine deficiency early in life impairs cognition and growth, but iodine status is also a key determinant of thyroid disorders in adults. Severe iodine deficiency causes goitre and hypothyroidism because, despite an increase in thyroid activity to maximise iodine uptake and recycling in this setting, iodine concentrations are still too low to enable production of thyroid hormone. In mild-to-moderate iodine deficiency, increased thyroid activity can compensate for low iodine intake and maintain euthyroidism in most individuals, but at a price: chronic thyroid stimulation results in an increase in the prevalence of toxic nodular goitre and hyperthyroidism in populations. This high prevalence of nodular autonomy usually results in a further increase in the prevalence of hyperthyroidism if iodine intake is subsequently increased by salt iodisation. However, this increase is transient because iodine sufficiency normalises thyroid activity which, in the long term, reduces nodular autonomy. Increased iodine intake in an iodine-deficient population is associated with a small increase in the prevalence of subclinical hypothyroidism and thyroid autoimmunity; whether these increases are also transient is unclear. Variations in population iodine intake do not affect risk for Graves' disease or thyroid cancer, but correction of iodine deficiency might shift thyroid cancer subtypes toward less malignant forms. Thus, optimisation of population iodine intake is an important component of preventive health care to reduce the prevalence of thyroid disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multipathway modulation of exercise and glucose stress effects upon GH secretion in healthy men.

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Veldhuis, Johannes D; Olson, Thomas P; Takahashi, Paul Y; Miles, John M; Joyner, Michael J; Yang, Rebecca J; Wigham, Jean

2015-09-01

Exercise evokes pulsatile GH release followed by autonegative feedback, whereas glucose suppresses GH release followed by rebound-like GH release (feedforward escape). Here we test the hypothesis that age, sex steroids, insulin, body composition and physical power jointly determine these dynamic GH responses. This was a prospectively randomized glucose-blinded study conducted in the Mayo Center for Advancing Translational Sciences in healthy men ages 19-77 years (N=23). Three conditions, fasting/rest/saline, fasting/exercise/saline and fasting/rest/iv glucose infusions, were used to drive GH dynamics during 10-min blood sampling for 6h. Linear correlation analysis was applied to relate peak/nadir GH dynamics to age, sex steroids, insulin, CT-estimated abdominal fat and physical power (work per unit time). Compared with the fasting/rest/saline (control) day, fasting/exercise/saline infusion evoked peak GH within 1h, followed by negative feedback 3-5h later. The dynamic GH excursion was strongly (R(2)=0.634) influenced by (i) insulin negatively (P=0.011), (ii) power positively (P=0.0008), and (iii) E2 positively (P=0.001). Dynamic glucose-modulated GH release was determined by insulin negatively (P=0.0039) and power positively (P=0.0034) (R(2)=0.454). Under rest/saline, power (P=0.031) and total abdominal fat (P=0.012) (R(2)=0.267) were the dominant correlates of GH excursions. In healthy men, dynamic GH perturbations induced by exercise and glucose are strongly related to physical power, insulin, estradiol, and body composition, thus suggesting a network of regulatory pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

Antimicrobial peptide GH12 suppresses cariogenic virulence factors of Streptococcus mutans

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Wang, Yufei; Wang, Xiuqing; Jiang, Wentao; Wang, Kun; Luo, Junyuan; Li, Wei; Zhou, Xuedong; Zhang, Linglin

2018-01-01

ABSTRACT Cariogenic virulence factors of Streptococcus mutans include acidogenicity, aciduricity, and extracellular polysaccharides (EPS) synthesis. The de novo designed antimicrobial peptide GH12 has shown bactericidal effects on S. mutans, but its interaction with virulence and regulatory systems of S. mutans remains to be elucidated. The objectives were to investigate the effects of GH12 on virulence factors of S. mutans, and further explore the function mechanisms at enzymatic and transcriptional levels. To avoid decrease in bacterial viability, we limited GH12 to subinhibitory levels. We evaluated effects of GH12 on acidogenicity of S. mutans by pH drop, lactic acid measurement and lactate dehydrogenase (LDH) assay, on aciduricity through survival rate at pH 5.0 and F1F0-ATPase assay, and on EPS synthesis using quantitative measurement, morphology observation, vertical distribution analyses and biomass calculation. Afterwards, we conducted quantitative real-time PCR to acquire the expression profile of related genes. GH12 at 1/2 MIC (4 mg/L) inhibited acid production, survival rate, EPS synthesis, and biofilm formation. The enzymatic activity of LDH and F1F0-ATPase was inhibited, and ldh, gtfBCD, vicR, liaR, and comDE genes were significantly downregulated. In conclusion, GH12 inhibited virulence factors of S. mutans, through reducing the activity of related enzymes, downregulating virulence genes, and inactivating specific regulatory systems. PMID:29503706

Structure of the GH1 domain of guanylate kinase-associated protein from Rattus norvegicus

International Nuclear Information System (INIS)

Tong, Junsen; Yang, Huiseon; Eom, Soo Hyun; Chun, ChangJu; Im, Young Jun

2014-01-01

Graphical abstract: - Highlights: • The crystal structure of GKAP homology domain 1 (GH1) was determined. • GKAP GH1 is a three-helix bundle connected by short flexible loops. • The predicted helix α4 associates weakly with the helix α3, suggesting dynamic nature of the GH1 domain. - Abstract: Guanylate-kinase-associated protein (GKAP) is a scaffolding protein that links NMDA receptor-PSD-95 to Shank–Homer complexes by protein–protein interactions at the synaptic junction. GKAP family proteins are characterized by the presence of a C-terminal conserved GKAP homology domain 1 (GH1) of unknown structure and function. In this study, crystal structure of the GH1 domain of GKAP from Rattus norvegicus was determined in fusion with an N-terminal maltose-binding protein at 2.0 Å resolution. The structure of GKAP GH1 displays a three-helix bundle connected by short flexible loops. The predicted helix α4 which was not visible in the crystal structure associates weakly with the helix α3 suggesting dynamic nature of the GH1 domain. The strict conservation of GH1 domain across GKAP family members and the lack of a catalytic active site required for enzyme activity imply that the GH1 domain might serve as a protein–protein interaction module for the synaptic protein clustering

Structure of the GH1 domain of guanylate kinase-associated protein from Rattus norvegicus

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Tong, Junsen; Yang, Huiseon [College of Pharmacy, Chonnam National University, Gwangju 500-757 (Korea, Republic of); Eom, Soo Hyun [School of Life Sciences, Steitz Center for Structural Biology, and Department of Chemistry, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of); Chun, ChangJu, E-mail: cchun1130@jnu.ac.kr [College of Pharmacy, Chonnam National University, Gwangju 500-757 (Korea, Republic of); Im, Young Jun, E-mail: imyoungjun@jnu.ac.kr [College of Pharmacy, Chonnam National University, Gwangju 500-757 (Korea, Republic of)

2014-09-12

Graphical abstract: - Highlights: • The crystal structure of GKAP homology domain 1 (GH1) was determined. • GKAP GH1 is a three-helix bundle connected by short flexible loops. • The predicted helix α4 associates weakly with the helix α3, suggesting dynamic nature of the GH1 domain. - Abstract: Guanylate-kinase-associated protein (GKAP) is a scaffolding protein that links NMDA receptor-PSD-95 to Shank–Homer complexes by protein–protein interactions at the synaptic junction. GKAP family proteins are characterized by the presence of a C-terminal conserved GKAP homology domain 1 (GH1) of unknown structure and function. In this study, crystal structure of the GH1 domain of GKAP from Rattus norvegicus was determined in fusion with an N-terminal maltose-binding protein at 2.0 Å resolution. The structure of GKAP GH1 displays a three-helix bundle connected by short flexible loops. The predicted helix α4 which was not visible in the crystal structure associates weakly with the helix α3 suggesting dynamic nature of the GH1 domain. The strict conservation of GH1 domain across GKAP family members and the lack of a catalytic active site required for enzyme activity imply that the GH1 domain might serve as a protein–protein interaction module for the synaptic protein clustering.

Growth hormone deficiency and central hypogonadism in retired professional football players

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Gábor László Kovács

2016-12-01

Full Text Available Purpose: The aim of this cross-sectional study was to evaluate the possible impact of multiple mild head traumas sustained during a long-term football career on the presence of central hypogonadism and growth hormone (GH deficiency. Methods: Twenty-seven retired, former professional male football players were investigated. All subjects were assessed for serum levels of insulin-like growth factor (IGF-1, luteinizing hormone (LH and total testosterone (TT. Quality of life was quantified using the Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA questionnaire. Results: Subjects had a median age of 48.0 (42.0 – 53.0 years and a median football career of 29.0 years (22.0 – 32.0. One subject had central hypogonadism and none had growth hormone deficiency. Nine subjects reported sport-related head injuries. We found a negative correlation between sport-related head injuries and serum LH (p = -0.459, P = 0.016. Subjects with a history of sport-related head injury had a median LH of 3.3 U/L (2.7 – 3.6, while those without a history of sport-related head injury had a median LH of 4.1 (U/L (3.6 – 5.7, P = 0.017. However, there were no differences in other hormones between the two groups. Moreover, we did not find any correlation between the duration of the player’s career nor their field position with hormone profiles or QoL-AGHDA. Conclusion: Although retired footfall players with a history of sport-related head injury had lower LH levels, we did not find strong evidence of an increased prevalence of central hypogonadism or GH deficiency in these patients. Our results suggest that a long-term football career, which includes headings and repetitive mild head traumas, does not damage the most vulnerable anterior pituitary cells.

Demographic factors influencing the GH system: Implications for the detection of GH doping in sport.

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Nelson, Anne E; Ho, Ken K Y

2009-08-01

Application of methods for detecting GH doping depend on being able to discriminate between abnormal levels due to doping and normal physiological levels of circulating proteins that change in response to exogenous administration. Constituents of the IGF and collagen systems have been shown to be promising markers of GH abuse. Their ultimate utility, however, depends on identification of the factors that regulate their concentrations in blood. Among these are demographic factors that are known to influence these markers in the general population. In a large cross-sectional study of the GH-responsive markers in over 1000 elite athletes from 12 countries representing 4 major ethnic groups and 10 sport types, we have shown that there is a significant negative correlation between age and all the IGF and collagen markers we studied, with a rapid decrease in early adolescence. Age was the major contribution to the variability, equivalent to >80% of the attributable variation in IGF-I and the collagen markers. The IGF axis markers were all significantly higher in women, and the collagen markers significantly higher in men, however, the contribution of gender was smaller than that of age, except for IGFBP-3 and ALS. BMI had a minor contribution to variability of the GH-responsive markers. After adjustment for the confounding influences of age, gender and BMI, the effect of ethnicity in elite athletes was trivial except for IGFBP-3 and ALS, which were both lower in Africans and higher in Caucasians. Compared to age and gender, the contribution of sport type was also modest. Our findings on the influence of age, gender, BMI and sport type have also been confirmed in a study of mostly Caucasian elite athletes in the post-competition setting. In conclusion, age and gender are the major determinants of variability for IGF-I and the collagen markers, whereas ethnicity and sport type have a minor influence. Therefore, a test based on IGF-I and the collagen markers must take age

Functional Role of N-Linked Glycosylation in Pseudorabies Virus Glycoprotein gH.

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Vallbracht, Melina; Rehwaldt, Sascha; Klupp, Barbara G; Mettenleiter, Thomas C; Fuchs, Walter

2018-05-01

Many viral envelope proteins are modified by asparagine (N)-linked glycosylation, which can influence their structure, physicochemical properties, intracellular transport, and function. Here, we systematically analyzed the functional relevance of N-linked glycans in the alphaherpesvirus pseudorabies virus (PrV) glycoprotein H (gH), which is an essential component of the conserved core herpesvirus fusion machinery. Upon gD-mediated receptor binding, the heterodimeric complex of gH and gL activates gB to mediate fusion of the viral envelope with the host cell membrane for viral entry. gH contains five potential N-linked glycosylation sites at positions 77, 162, 542, 604, and 627, which were inactivated by conservative mutations (asparagine to glutamine) singly or in combination. The mutated proteins were tested for correct expression and fusion activity. Additionally, the mutated gH genes were inserted into the PrV genome for analysis of function during virus infection. Our results demonstrate that all five sites are glycosylated. Inactivation of the PrV-specific N77 or the conserved N627 resulted in significantly reduced in vitro fusion activity, delayed penetration kinetics, and smaller virus plaques. Moreover, substitution of N627 greatly affected transport of gH in transfected cells, resulting in endoplasmic reticulum (ER) retention and reduced surface expression. In contrast, mutation of N604, which is conserved in the Varicellovirus genus, resulted in enhanced in vitro fusion activity and viral cell-to-cell spread. These results demonstrate a role of the N-glycans in proper localization and function of PrV gH. However, even simultaneous inactivation of all five N-glycosylation sites of gH did not severely inhibit formation of infectious virus particles. IMPORTANCE Herpesvirus infection requires fusion of the viral envelope with cellular membranes, which involves the conserved fusion machinery consisting of gB and the heterodimeric gH/gL complex. The bona fide

Excessive growth hormone expression in male GH transgenic mice adversely alters bone architecture and mechanical strength.

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Lim, S V; Marenzana, M; Hopkinson, M; List, E O; Kopchick, J J; Pereira, M; Javaheri, B; Roux, J P; Chavassieux, P; Korbonits, M; Chenu, C

2015-04-01

Patients with acromegaly have a higher prevalence of vertebral fractures despite normal bone mineral density (BMD), suggesting that GH overexpression has adverse effects on skeletal architecture and strength. We used giant bovine GH (bGH) transgenic mice to analyze the effects of high serum GH levels on BMD, architecture, and mechanical strength. Five-month-old hemizygous male bGH mice were compared with age- and sex-matched nontransgenic littermates controls (NT; n=16/group). Bone architecture and BMD were analyzed in tibia and lumbar vertebrae using microcomputed tomography. Femora were tested to failure using three-point bending and bone cellular activity determined by bone histomorphometry. bGH transgenic mice displayed significant increases in body weight and bone lengths. bGH tibia showed decreases in trabecular bone volume fraction, thickness, and number compared with NT ones, whereas trabecular pattern factor and structure model index were significantly increased, indicating deterioration in bone structure. Although cortical tissue perimeter was increased in transgenic mice, cortical thickness was reduced. bGH mice showed similar trabecular BMD but reduced trabecular thickness in lumbar vertebra relative to controls. Cortical BMD and thickness were significantly reduced in bGH lumbar vertebra. Mechanical testing of femora confirmed that bGH femora have decreased intrinsic mechanical properties compared with NT ones. Bone turnover is increased in favor of bone resorption in bGH tibia and vertebra compared with controls, and serum PTH levels is also enhanced in bGH mice. These data collectively suggest that high serum GH levels negatively affect bone architecture and quality at multiple skeletal sites.

Epidemiology of SHOX deficiency.

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Nicolosi, A; Caruso-Nicoletti, M

2010-06-01

Deletion of short stature homeobox-containing (SHOX) gene, in the pseudoautosomal region (PAR1) of X and Y chromosomes, is an important cause of short stature. Homozygous loss of SHOX results in the more severe Langer mesomelic dysplasia, while SHOX haploinsufficiency cause a wide spectrum of short stature phenotypes, including patients with Turner syndrome, Leri Weill dyschondrosteosis (LWD), and idiopathic short stature (ISS). In Turner syndrome, haploinsufficiency of SHOX gene, as well as short stature, are present in 100%; nevertheless, SHOX deficiency accounts for only two-thirds of Turner patients' short stature. In LWD the prevalence of SHOX gene anomalies varies from 56% to 100%. This wide range might be due to different factors such as selection criteria of patients, sample size, and method used for screening SHOX mutations. The real challenge is to establish the prevalence of SHOX deficiency in ISS children given that published studies have reported this association with a very broad frequency range varying from 1.5% to 15%. An important variable in these studies is represented by the method used for screening SHOX mutations and sometimes by differences in patient selection. Short stature is present by definition in 3 out of 100 subjects; if we consider a frequency of SHOX defects of 3% among ISS, we should expect a population prevalence of 1 in 1000. This prevalence would be higher than that of GH deficiency (1:3,500) and of Turner syndrome (1:2,500 females), suggesting that SHOX deficiency could be one of the most frequent monogenetic causes of short stature.

Effect of rTMP-GH recombinant fusion protein on thrombocytopoiesis in irradiation injured mice

International Nuclear Information System (INIS)

Xu Yang; Wang Junping; Chen Fang; Shen Mingqiang; Chen Mo; Wang Song; Ran Xinze; Su Yongping; Kai Li

2009-01-01

Objective: To investigate the in vivo effects of rTMP-GH recombinant fusion protein on thrombocytopoiesis in mice with thrombopenia inflicted by irradiation. Methods: BALB/C mice weighting around 20 g were irradiated with 5 Gy of 60 Co γ-ray irradiation to generate thrombopenia. The irradiation injured mice were injected with rTMP-GH or rhGH subcutaneously at the dose of 200 (μg ·kg -1 · d -1 for 7 days. From the 6 th day, the platelets in blood samples from vena caudalis were counted routinely, and the pathological changes of bone marrow were determined by morphological observation. Results: From the 10 th day, the levels of blood platelet in rTMP-GH treated mice were much higher than those of rhGH treatment group and normal saline (NS) control group, especially at the nadir (P < 0.01). On the 22 nd day, the platelet count has recovered up to 80% of normal level in rTMP-GH treatment group, while it has just recovered up to 30% in NS control group. Morphological observation showed that there was obvious reconstruction of bone marrow in mice treated with rTMP-GH, compared with NS group.The number of megarkaryoblasts and megakaryocytes in bone marrow of rTMP-GH treated mice (3.07 ± 0.32) was much higher than those of rhGH treatment group (2.20 ± 0.22, P < 0.05) and NS control group (0.87 ± 0.19, P <0.01). Conclusions: rTMP-GH has potent effects on the recovery of blood platelet by promoting megarkaryocytopoiesis in irradiation injuried mice. (authors)

Mild pituitary phenotype in 3- and 12-month-old Aip-deficient male mice.

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Lecoq, Anne-Lise; Zizzari, Philippe; Hage, Mirella; Decourtye, Lyvianne; Adam, Clovis; Viengchareun, Say; Veldhuis, Johannes D; Geoffroy, Valérie; Lombès, Marc; Tolle, Virginie; Guillou, Anne; Karhu, Auli; Kappeler, Laurent; Chanson, Philippe; Kamenický, Peter

2016-10-01

Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene predispose humans to pituitary adenomas, particularly of the somatotroph lineage. Mice with global heterozygous inactivation of Aip (Aip(+/-)) also develop pituitary adenomas but differ from AIP-mutated patients by the high penetrance of pituitary disease. The endocrine phenotype of these mice is unknown. The aim of this study was to determine the endocrine phenotype of Aip(+/-) mice by assessing the somatic growth, ultradian pattern of GH secretion and IGF1 concentrations of longitudinally followed male mice at 3 and 12 months of age. As the early stages of pituitary tumorigenesis are controversial, we also studied the pituitary histology and somatotroph cell proliferation in these mice. Aip(+/-) mice did not develop gigantism but exhibited a leaner phenotype than wild-type mice. Analysis of GH pulsatility by deconvolution in 12-month-old Aip(+/-) mice showed a mild increase in total GH secretion, a conserved GH pulsatility pattern, but a normal IGF1 concentration. No pituitary adenomas were detected up to 12 months of age. An increased ex vivo response to GHRH of pituitary explants from 3-month-old Aip(+/-) mice, together with areas of enlarged acini identified on reticulin staining in the pituitary of some Aip(+/-) mice, was suggestive of somatotroph hyperplasia. Global heterozygous Aip deficiency in mice is accompanied by subtle increase in GH secretion, which does not result in gigantism. The absence of pituitary adenomas in 12-month-old Aip(+/-) mice in our experimental conditions demonstrates the important phenotypic variability of this congenic mouse model. © 2016 Society for Endocrinology.

Arginine induces GH gene expression by activating NOS/NO signaling in rat isolated hemi-pituitaries

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S.C.F. Olinto

2012-11-01

Full Text Available The amino acid arginine (Arg is a recognized secretagogue of growth hormone (GH, and has been shown to induce GH gene expression. Arg is the natural precursor of nitric oxide (NO, which is known to mediate many of the effects of Arg, such as GH secretion. Arg was also shown to increase calcium influx in pituitary cells, which might contribute to its effects on GH secretion. Although the mechanisms involved in the effects of Arg on GH secretion are well established, little is known about them regarding the control of GH gene expression. We investigated whether the NO pathway and/or calcium are involved in the effects of Arg on GH gene expression in rat isolated pituitaries. To this end, pituitaries from approximately 170 male Wistar rats (~250 g were removed, divided into two halves, pooled (three hemi-pituitaries and incubated or not with Arg, as well as with different pharmacological agents. Arg (71 mM, the NO donor sodium nitroprusside (SNP, 1 and 0.1 mM and a cyclic guanosine monophosphate (cGMP analogue (8-Br-cGMP, 1 mM increased GH mRNA expression 60 min later. The NO acceptor hemoglobin (0.3 µM blunted the effect of SNP, and the combined treatment with Arg and L-NAME (a NO synthase (NOS inhibitor, 55 mM abolished the stimulatory effect of Arg on GH gene expression. The calcium channel inhibitor nifedipine (3 µM also abolished Arg-induced GH gene expression. The present study shows that Arg directly induces GH gene expression in hemi-pituitaries isolated from rats, excluding interference from somatostatinergic neurons, which are supposed to be inhibited by Arg. Moreover, the data demonstrate that the NOS/NO signaling pathway and calcium mediate the Arg effects on GH gene expression.

Arginine induces GH gene expression by activating NOS/NO signaling in rat isolated hemi-pituitaries

Energy Technology Data Exchange (ETDEWEB)

Olinto, S.C.F. [Faculdade de Ciências Integradas do Pontal, Universidade Federal de Uberlândia, Ituiutaba, MG (Brazil); Adrião, M.G. [Departamento de Morfologia e Fisiologia, Universidade Federal Rural de Pernambuco, Recife, PE (Brazil); Castro-Barbosa, T.; Goulart-Silva, F.; Nunes, M.T. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil)

2012-06-01

The amino acid arginine (Arg) is a recognized secretagogue of growth hormone (GH), and has been shown to induce GH gene expression. Arg is the natural precursor of nitric oxide (NO), which is known to mediate many of the effects of Arg, such as GH secretion. Arg was also shown to increase calcium influx in pituitary cells, which might contribute to its effects on GH secretion. Although the mechanisms involved in the effects of Arg on GH secretion are well established, little is known about them regarding the control of GH gene expression. We investigated whether the NO pathway and/or calcium are involved in the effects of Arg on GH gene expression in rat isolated pituitaries. To this end, pituitaries from approximately 170 male Wistar rats (∼250 g) were removed, divided into two halves, pooled (three hemi-pituitaries) and incubated or not with Arg, as well as with different pharmacological agents. Arg (71 mM), the NO donor sodium nitroprusside (SNP, 1 and 0.1 mM) and a cyclic guanosine monophosphate (cGMP) analogue (8-Br-cGMP, 1 mM) increased GH mRNA expression 60 min later. The NO acceptor hemoglobin (0.3 µM) blunted the effect of SNP, and the combined treatment with Arg and L-NAME (an NO synthase (NOS) inhibitor, 55 mM) abolished the stimulatory effect of Arg on GH gene expression. The calcium channel inhibitor nifedipine (3 µM) also abolished Arg-induced GH gene expression. The present study shows that Arg directly induces GH gene expression in hemi-pituitaries isolated from rats, excluding interference from somatostatinergic neurons, which are supposed to be inhibited by Arg. Moreover, the data demonstrate that the NOS/NO signaling pathway and calcium mediate the Arg effects on GH gene expression.

Arginine induces GH gene expression by activating NOS/NO signaling in rat isolated hemi-pituitaries

International Nuclear Information System (INIS)

Olinto, S.C.F.; Adrião, M.G.; Castro-Barbosa, T.; Goulart-Silva, F.; Nunes, M.T.

2012-01-01

The amino acid arginine (Arg) is a recognized secretagogue of growth hormone (GH), and has been shown to induce GH gene expression. Arg is the natural precursor of nitric oxide (NO), which is known to mediate many of the effects of Arg, such as GH secretion. Arg was also shown to increase calcium influx in pituitary cells, which might contribute to its effects on GH secretion. Although the mechanisms involved in the effects of Arg on GH secretion are well established, little is known about them regarding the control of GH gene expression. We investigated whether the NO pathway and/or calcium are involved in the effects of Arg on GH gene expression in rat isolated pituitaries. To this end, pituitaries from approximately 170 male Wistar rats (∼250 g) were removed, divided into two halves, pooled (three hemi-pituitaries) and incubated or not with Arg, as well as with different pharmacological agents. Arg (71 mM), the NO donor sodium nitroprusside (SNP, 1 and 0.1 mM) and a cyclic guanosine monophosphate (cGMP) analogue (8-Br-cGMP, 1 mM) increased GH mRNA expression 60 min later. The NO acceptor hemoglobin (0.3 µM) blunted the effect of SNP, and the combined treatment with Arg and L-NAME (an NO synthase (NOS) inhibitor, 55 mM) abolished the stimulatory effect of Arg on GH gene expression. The calcium channel inhibitor nifedipine (3 µM) also abolished Arg-induced GH gene expression. The present study shows that Arg directly induces GH gene expression in hemi-pituitaries isolated from rats, excluding interference from somatostatinergic neurons, which are supposed to be inhibited by Arg. Moreover, the data demonstrate that the NOS/NO signaling pathway and calcium mediate the Arg effects on GH gene expression

Urinary growth hormone level and insulin-like growth factor-1 standard deviation score (IGF-SDS) can discriminate adult patients with severe growth hormone deficiency.

Science.gov (United States)

Hirohata, Toshio; Saito, Nobuhito; Takano, Koji; Yamada, So; Son, Jae-Hyun; Yamada, Shoko M; Nakaguchi, Hiroshi; Hoya, Katsumi; Murakami, Mineko; Mizutani, Akiko; Okinaga, Hiroko; Matsuno, Akira

2013-01-01

Adult growth hormone (GH) deficiency (AGHD) in Japan is diagnosed based on peak GH concentrations during GH provocative tests such as GHRP-2 stimulation test. In this study, we aimed to evaluate the ability of serum insulin-like growth factor-1 (sIGF-1) and urinary GH (uGH) at the time of awakening to diagnose AGHD. Fifty-nine patients with pituitary disease (32 men and 27 women; age 20-85 y (57.5 ± 15.5, mean ± SD) underwent GHRP-2 stimulation and sIGF-1 testing. Thirty-six and 23 patients were diagnosed with and without severe AGHD, respectively based on a peak GH response of standard deviation score (IGF-1 SDS) based on age and sex. We determined whether uGH levels in urine samples from 42 of the 59 patients at awakening were above or below the sensitivity limit. We evaluated IGF-1 SDS and uGH levels in a control group of 15 healthy volunteers. Values for IGF-1 SDS were significantly lower in patients with, than without (-2.07 ± 1.77 vs.-0.03 ± 0.92, mean ± SD; p -1.4. IGF-1 SDS discriminated AGHD more effectively in patients aged ≤60 years. The χ2 test revealed a statistical relationship between uGH and AGHD (test statistic: 7.0104 ≥ χ2 (1; 0.01) = 6.6349). When IGF-1 SDS is < -1.4 or uGH is below the sensitivity limit, AGHD can be detected with high sensitivity.

Transient hypothyroidism in the newborn: to treat or not to treat

Science.gov (United States)

Kanike, Neelakanta; Davis, Ajuah

2017-01-01

Transient congenital hypothyroidism (CH) refers to a temporary deficiency of thyroid hormone identified after birth, with low thyroxine (T4) and elevated thyrotropin (TSH), which later recovers to improved thyroxine production, typically in first few months of infancy. Approximately 17% to 40% of children diagnosed with CH by newborn screening (NBS) programs were later determined to have transient hypothyroidism. Causes of transient CH are prematurity, iodine deficiency, maternal thyrotropin receptor blocking antibodies, maternal intake of anti-thyroid drugs, maternal or neonatal iodine exposure, loss of function mutations and hepatic hemangiomas. The classic clinical symptoms and signs of CH are usually absent immediately after birth in vast majority of infants due to temporary protection from maternal thyroxine. NBS has been largely successful in preventing intellectual disability by early detection of CH by performing thyroid function tests in infants with abnormal screening results. In this review we present the evidence for decision making regarding treatment vs. withholding treatment in infants with transient CH and present a rational approach to identifying transient CH based on American Academy of Pediatrics (AAP) recommendation. PMID:29184815

Carbohydrate metabolism during long-term growth hormone (GH) treatment and after discontinuation of GH treatment in girls with Turner syndrome participating in a randomized dose-response study. Dutch Advisory Group on Growth Hormone

NARCIS (Netherlands)

T.C.J. Sas (Theo); S.M.P.F. de Muinck Keizer-Schrama (Sabine); Th. Stijnen (Theo); H-J. Aanstoot (Henk-Jan); S.L.S. Drop (Stenvert)

2000-01-01

textabstractTo assess possible side-effects of GH treatment with supraphysiological doses on carbohydrate (CH) metabolism in girls with Turner syndrome (TS) during long term GH treatment and after discontinuation of GH treatment, the results of oral glucose tolerance

Adiponectin in mice with altered GH action: links to insulin sensitivity and longevity?

Science.gov (United States)

Lubbers, Ellen R; List, Edward O; Jara, Adam; Sackman-Sala, Lucila; Cordoba-Chacon, Jose; Gahete, Manuel D; Kineman, Rhonda D; Boparai, Ravneet; Bartke, Andrzej; Kopchick, John J; Berryman, Darlene E

2013-03-01

Adiponectin is positively correlated with longevity and negatively correlated with many obesity-related diseases. While there are several circulating forms of adiponectin, the high-molecular-weight (HMW) version has been suggested to have the predominant bioactivity. Adiponectin gene expression and cognate serum protein levels are of particular interest in mice with altered GH signaling as these mice exhibit extremes in obesity that are positively associated with insulin sensitivity and lifespan as opposed to the typical negative association of these factors. While a few studies have reported total adiponectin levels in young adult mice with altered GH signaling, much remains unresolved, including changes in adiponectin levels with advancing age, proportion of total adiponectin in the HMW form, adipose depot of origin, and differential effects of GH vs IGF1. Therefore, the purpose of this study was to address these issues using assorted mouse lines with altered GH signaling. Our results show that adiponectin is generally negatively associated with GH activity, regardless of age. Further, the amount of HMW adiponectin is consistently linked with the level of total adiponectin and not necessarily with previously reported lifespan or insulin sensitivity of these mice. Interestingly, circulating adiponectin levels correlated strongly with inguinal fat mass, implying that the effects of GH on adiponectin are depot specific. Interestingly, rbGH, but not IGF1, decreased circulating total and HMW adiponectin levels. Taken together, these results fill important gaps in the literature related to GH and adiponectin and question the frequently reported associations of total and HMW adiponectin with insulin sensitivity and longevity.

STIMULASI PERTUMBUHAN JUVENIL ABALON, Haliotis squamata DENGAN PEMBERIAN HORMON REKOMBINAN IKAN rElGH

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Fitriyah Husnul Khotimah

2017-01-01

Full Text Available Masalah yang paling utama dalam budidaya abalon tropis adalah pertumbuhan yang lambat. Penggunaan rElGH (recombinant giant grouper, Epinephelus lanceolatus growth hormone untuk menstimulasi pertumbuhan beberapa spesies ikan sudah dilakukan. Penelitian ini bertujuan untuk menguji akselerasi pertumbuhan juvenil abalon tropis, Haliotis squamata setelah diberi perlakuan perendaman hormon rekombinan ikan kerapu kertang, Epinephelus lanceolatus pada frekuensi yang berbeda. Ada empat perlakuan frekuensi perendaman rElGH yaitu 4, 9, 16 kali, dan tanpa perendaman (kontrol. Masing-masing perlakuan diulang tiga kali. Perendaman dilakukan selama tiga jam, dengan interval waktu empat hari. Kepadatan abalon tropis 100 ekor/L air laut yang mengandung 30 mg rElGH. Wadah untuk perendaman berupa beaker glass yang dilengkapi dengan aerasi. Penelitian dilakukan selama tujuh bulan. Hasil penelitian menunjukkan bahwa abalon tropis yang direndam rElGH dengan frekuensi empat kali menghasilkan pertumbuhan bobot tubuh dan panjang cangkang tertinggi dan berbeda nyata dengan perlakuan lainnya (P<0,05. Sintasan abalon tropis yang diberi perlakuan perendaman hormon rElGH lebih tinggi dibandingkan perlakuan kontrol. The most crucial problem in tropical abalone aquaculture is the slow growth of the species. Studies investigating the use of rElGH (recombinant giant grouper, Epinephelus lanceolatus growth hormone for promoting growth have been performed in various species. This research aimed to examine the growth acceleration of tropical abalone, Haliotis squamata juvenile after being treated in different immersion frequencies of recombinant giant grouper, Epinephelus lanceolatus growth hormone (rElGH. There were four treatments of rElGH immersion frequency: 4, 9, 16 times and without rElGH immersion (control. Each treatment was performed in triplicates. Immersion was performed for 3 hours, at 4-day intervals and a density of 100 tropical abalones in 1 L seawater containing 30

Pegylated Long-Acting Human Growth Hormone Possesses a Promising Once-Weekly Treatment Profile, and Multiple Dosing Is Well Tolerated in Adult Patients with Growth Hormone Deficiency

DEFF Research Database (Denmark)

Søndergaard, Esben; Klose, Marianne Christina; Hansen, Mette

2011-01-01

Background: Recombinant human GH (rhGH) replacement therapy in children and adults currently requires daily sc injections for several years or lifelong, which may be both inconvenient and distressing for patients. NNC126-0083 is a pegylated rhGH developed for once-weekly administration. Objectives......: Our objective was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of NNC126-0083 in adult patients with GH deficiency (GHD). Subjects and Methods: Thirty-three adult patients with GHD, age 20-65 yr, body mass index 18.5-35.0 kg/m(2), and glycated...... to 240 h after the third dosing. Physical examination, antibodies, and local tolerability were assessed. Results: NNC126-0083 was well tolerated with no difference in local tolerability compared with placebo and with no signs of lipoatrophy. A more than dose-proportional exposure was observed...

Natural history of the classical form of primary growth hormone (GH) resistance (Laron syndrome).

Science.gov (United States)

Laron, Z

1999-04-01

A description of the clinical, biochemical and endocrinological features of the classical form of the syndrome of primary growth hormone (GH) resistance (Laron syndrome) is presented including the progressive changes during follow-up from infancy into adulthood. The main diagnostic features are: severe growth retardation, acromicria, small gonads and genitalia, and obesity. Serum GH levels are elevated and insulin-like growth factor-I (IGF-I) values are low and do not rise upon stimulation by exogenous hGH. The pathogenesis of this syndrome is due to various molecular defects from exon deletion to nonsense, frameshift, splice and missense mutations in the GH receptor (GH-R) gene or in its post-receptor pathways.

Expression and ontogeny of growth hormone (Gh) in the protogynous hermaphroditic ricefield eel (Monopterus albus).

Science.gov (United States)

Chen, Dong; Liu, Jiang; Chen, Wanping; Shi, Shuxia; Zhang, Weimin; Zhang, Lihong

2015-12-01

Growth hormone (GH) is a single-chain polypeptide hormone mainly secreted by somatotropes of the anterior pituitary gland and is an important regulator of somatic growth in vertebrates including teleosts. In this study, a polyclonal antiserum against ricefield eel Gh was generated and the expression of Gh at the mRNA and protein levels was analyzed. Both RT-PCR and western blot analysis showed that Gh was predominantly expressed in the pituitary glands of ricefield eels. The immunoreactive Gh signals were localized to the multicellular layers of the adenohypophysis adjacent to the neurohypophysis in ricefield eels. Ontogenetic analysis showed that immunoreactive Gh signals could be detected in the pituitary glands of ricefield eel embryos as early as 3 days post-fertilization. During the sex change from female to male, the levels of the immunoreactive Gh signals in the pituitary glands of the ricefield eels peaked at the intersexual stage. These results suggest that Gh in the pituitary glands may be associated with embryonic development before hatching, as well as with the sex change in the adult ricefield eels, possibly via the classical endocrine manner.

Growth Hormone Deficiency in a Child with Neurofibromatosis-Noonan Syndrome.

Science.gov (United States)

Vurallı, Doğuş; Gönç, Nazlı; Vidaud, Dominique; Özön, Alev; Alikaşifoğlu, Ayfer; Kandemir, Nurgün

2016-03-05

Neurofibromatosis-Noonan syndrome (NFNS) is a distinct entity which shows the features of both NF1 (neurofibromatosis 1) and Noonan syndrome (NS). While growth hormone deficiency (GHD) has been relatively frequently identified in NF1 and NS patients, there is limited experience in NFNS cases. The literature includes only one case report of a NFNS patient having GHD and that report primarily focuses on the dermatological lesions that accompany the syndrome and not on growth hormone (GH) treatment. Here, we present a 13-year-old girl who had clinical features of NFNS with a mutation in the NF1 gene. The case is the first NFNS patient reported in the literature who was diagnosed to have GHD and who received GH treatment until reaching final height. The findings in this patient show that short stature is a feature of NFNS and can be caused by GHD. Patients with NFNS who show poor growth should be evaluated for GHD.

Aerosol Observing System Greenhouse Gas (AOS GhG) Handbook

Energy Technology Data Exchange (ETDEWEB)

Biraud, S. C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Reichl, K. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2016-03-01

The Greenhouse Gas (GhG) Measurement system is a combination of two systems in series: (1) the Tower Gas Processing (TGP) System, an instrument rack which pulls, pressurizes, and dries air streams from an atmospheric sampling tower through a series of control and monitoring components, and (2) the Picarro model G2301 cavity ringdown spectrometer (CRDS), which measures CO2, CH4, and H2O vapor; the primary measurements of the GhG system.

IGF-I deficiency, longevity and cancer protection of patients with Laron syndrome.

Science.gov (United States)

Laron, Zvi; Kauli, Rivka; Lapkina, Lena; Werner, Haim

Laron syndrome (LS) is a unique model of congenital IGF-I deficiency. It is characterized by dwarfism and obesity, and is caused by deletion or mutations of the growth hormone receptor (GH-R) gene. It is hypothesized that LS is an old disease originating in Indonesia and that the mutated gene spread to South Asia, the Middle East, the Mediterranean region and South America. Copyright © 2016 Elsevier B.V. All rights reserved.

IDENTIFICATION OF GH|ALUI AND GHR|ALUI GENES POLYMORPHISMS IN INDONESIAN BUFFALO

Directory of Open Access Journals (Sweden)

E. Andreas

2014-10-01

Full Text Available Growth hormone (GH is an anabolic hormone which sintesized and secreted by somatrotop cell inpituitary anterior lobe. GH exert its effect on growth and metabolism by interacting with a specificreceptor on the surface of the target cells. Growth hormone receptor (GHR has been suggested ascandidate gene for traits related to meat production in Bovidae. The objectives of this study were toidentify polymorphism of GH and GHR genes in buffalo. The 452 DNA samples buffalo were collectedfrom five populations in Indonesia (Siborong-Borong-Medan (65, Lebak-Banten (29, Pandeglang-Banten (180, Semarang-Central Java, and Mataram-West Nusa Tenggara (103. A gene fragment of theGH|AluI gene at 432 bp located on exon 3 and GHR|AluI gene at 298 bp on exon 10 were successfullyamplified by using the techniques of a PCR (polymerase chain reaction and genotyped by PCR-RFLP(restriction fragment length polymorphism then -SSCP (single strand conformation polymorphism. Theresults showed no polymorphisms were detected in these genes. All buffaloes tested had LL genotype forlocus GH|AluI and AA genotype for locus GHR|AluI.

Effects of GhWUS from upland cotton (Gossypium hirsutum L.) on somatic embryogenesis and shoot regeneration.

Science.gov (United States)

Xiao, Yanqing; Chen, Yanli; Ding, Yanpeng; Wu, Jie; Wang, Peng; Yu, Ya; Wei, Xi; Wang, Ye; Zhang, Chaojun; Li, Fuguang; Ge, Xiaoyang

2018-05-01

The WUSCHEL (WUS) gene encodes a plant-specific homeodomain-containing transcriptional regulator, which plays important roles during embryogenesis, as well as in the formation of shoot and flower meristems. Here, we isolated two homologues of Arabidopsis thaliana WUS (AtWUS), GhWUS1a_At and GhWUS1b_At, from upland cotton (Gossypium hirsutum). Domain analysis suggested that the two putative GhWUS proteins contained a highly conserved DNA-binding HOX domain and a WUS-box. Expression profile analysis showed that GhWUSs were predominantly expressed during the embryoid stage. Ectopic expression of GhWUSs in Arabidopsis could induce somatic embryo and shoot formation from seedling root tips. Furthermore, in the absence of exogenous hormone, overexpression of GhWUSs in Arabidopsis could promote shoot regeneration from excised roots, and in the presence of exogenous auxin, excised roots expressing GhWUS could be induced to produce somatic embryo. In addition, expression of the chimeric GhWUS repressor in cotton callus inhibited embryogenic callus formation. Our results show that GhWUS is an important regulator of somatic embryogenesis and shoot regeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

Low plasma lecithin : cholesterol acyltransferase and lipid transfer protein activities in growth hormone deficient and acromegalic men: role in altered high density lipoproteins

NARCIS (Netherlands)

Beentjes, JAM; van Tol, A; Sluiter, WJ; Dullaart, RPF

2000-01-01

Growth hormone (GH) deficiency and acromegaly may be associated with increased cardiovascular risk. Little is known about alterations in high density lipoproteins (HDL) in these conditions. Lecithin:cholesterol acyl transferase (LCAT) has the ability to esterify free cholesterol (FC) in HDL.

Growth hormone replacement normalizes impaired fibrinolysis: new insights into endothelial dysfunction in patients with hypopituitarism and growth hormone deficiency.

Science.gov (United States)

Miljic, D; Miljic, P; Doknic, M; Pekic, S; Stojanovic, M; Cvijovic, G; Micic, D; Popovic, V

2013-12-01

Cardiovascular morbidity in adult patients with growth hormone deficiency (GHD) and hypopituitarism is increased. Clustering of cardiovascular risk factors leading to endothelial dysfunction and impaired fibrinolysis has also been reported and may account for progression to overt vascular changes in these patients. However, effect of long lasting GH replacement therapy on fibrinolytic capacity in GH deficient patients has not been investigated so far. To investigate fibrinolysis before and after challenge with venous occlusion in GHD patients with hypopituitarism before and during one year of growth hormone replacement. Hospital based, interventional, prospective study. Twenty one patient with GHD and fourteen healthy control subjects matched for age, sex and body mass index (BMI). Anthropometric, metabolic and fibrinolytic parameters were measured at the start and after three, six and twelve months of treatment with human recombinant GH. At baseline GHD patients had significantly impaired fibrinolysis compared to healthy persons. During treatment with GH, significant changes were observed in insulin like growth factor 1(IGF-1) [from baseline 6.9(2.4-13.5) to 22.0(9.0-33.0) nmol/l after one month of treatment; p<0.01] and fibrinolysis. Improvement in fibrinolysis was mostly attributed to improvement of stimulated endothelial tissue plasminogen activator (t-PA) release in response to venous occlusion [from baseline 1.1(0.4-2.6) to 1.9(0.5-8.8) after one year of treatment; p<0.01]. Growth hormone replacement therapy has favorable effects on t-PA release from endothelium and net fibrinolytic capacity in GHD adults, which may contribute to decrease their risk of vascular complications. © 2013.

Hat das humane Wachtumshormon (hGH eine Relevanz in der Kontrolle der penilen Erektion?

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Ückert St

2003-01-01

Full Text Available Allgemeines: Schon seit langem wird die Frage einer Beteiligung des Hypophysenhormons Human Growth Hormone (Wachstumshormon, hGH, GH an der Kontrolle der sexuellen Maturation und der Reproduktionsfunktion des Menschen diskutiert. Die Symptome eines GH-Defizits beim Mann sind u. a. allgemeine Antriebslosigkeit, Oligo- oder Azoospermie, eine Verminderung der Libido sowie eine Beeinträchtigung der normalen Erektionsfähigkeit. Es wird vermutet, daß die biologischen Effekte des GH eine durch das Somatomedin Insulin-like Growth Factor 1 (IGF-1 vermittelte Stimulation der Produktion von Stickoxid (NO durch die endotheliale und neuronale Form des Enzyms NO-Synthase einschließen. So konnte gezeigt werden, daß physiologische Konzentrationen von GH den adrenergen Tonus isolierter Streifenpräparate humaner Schwellkörpermuskulatur antagonisieren und den Gewebegehalt des Second Messengers cGMP erhöhen. Im Rahmen dieser Studie haben wir in einem Kollektiv gesunder Männer und in einer Gruppe von Patienten mit erektiler Dysfunktion (ED die systemischen und cavernösen Serumkonzentrationen von GH während verschiedener peniler Funktionszustände, d. h. verschiedener Stadien der sexuellen Erregung, untersucht. Methoden: 35 gesunden männlichen Probanden und 45 Patienten mit einer ED organogener oder psychogener Genese wurden während der penilen Flakzidität, Tumeszenz, Rigidität - dieses Stadium wurde nur von den Gesunden erreicht - und Detumeszenz zeitgleich Blutproben aus einer Cubitalvene und dem Corpus cavernosum penis entnommen. Tumeszenz und Rigidität wurden durch visuelle und taktile Stimulation ausgelöst. Die Quantifizierung von GH in Aliquots der Serumfraktionen erfolgte mit immunradiometrischen Methoden (IRMA. Ergebnisse: In der Gruppe der gesunden Männer stieg die mittlere systemische und cavernöse Serumkonzentration von GH während der Tumeszenz an, während in den Phasen der Rigidität und Detumeszenz eine Abnahme registriert wurde

Disruption of the GH Receptor Gene in Adult Mice Increases Maximal Lifespan in Females

DEFF Research Database (Denmark)

Junnila, Riia K.; Duran-Ortiz, Silvana; Suer, Ozan

2016-01-01

GH and IGF-1 are important for a variety of physiological processes including growth, development, and aging. Mice with reduced levels of GH and IGF-1 have been shown to live longer than wild-type controls. Our laboratory has previously found that mice with a GH receptor gene knockout (GHRKO) fro...

Targeting either GH or IGF-I during somatostatin analogue treatment in patients with acromegaly

DEFF Research Database (Denmark)

Dal, Jakob; Klose, Marianne; Heck, Ansgar

2018-01-01

CONTEXT: Discordant GH and IGF-I values are frequent in acromegaly. The clinical significance and its dependence on treatment modality and of glucose-suppressed GH (GHnadir) measurements remain uncertain. OBJECTIVE: To evaluate the effects of targeting either IGF-I or GH during somatostatin analog...... (SA) treatment. PATIENTS AND METHODS: 84 patients with controlled acromegaly after surgery (n=23) or SA (n=61) underwent a GH-profile including an OGTT, at baseline and after 12 months. SA patients were randomized to monitoring according to either IGF-I (n= 33) or GHnadir (n=28). SA dose escalation...

Genome-wide analysis of the GH3 family in apple (Malus × domestica).

Science.gov (United States)

Yuan, Huazhao; Zhao, Kai; Lei, Hengjiu; Shen, Xinjie; Liu, Yun; Liao, Xiong; Li, Tianhong

2013-05-02

Auxin plays important roles in hormone crosstalk and the plant's stress response. The auxin-responsive Gretchen Hagen3 (GH3) gene family maintains hormonal homeostasis by conjugating excess indole-3-acetic acid (IAA), salicylic acid (SA), and jasmonic acids (JAs) to amino acids during hormone- and stress-related signaling pathways. With the sequencing of the apple (Malus × domestica) genome completed, it is possible to carry out genomic studies on GH3 genes to indentify candidates with roles in abiotic/biotic stress responses. Malus sieversii Roem., an apple rootstock with strong drought tolerance and the ancestral species of cultivated apple species, was used as the experimental material. Following genome-wide computational and experimental identification of MdGH3 genes, we showed that MdGH3s were differentially expressed in the leaves and roots of M. sieversii and that some of these genes were significantly induced after various phytohormone and abiotic stress treatments. Given the role of GH3 in the negative feedback regulation of free IAA concentration, we examined whether phytohormones and abiotic stresses could alter the endogenous auxin level. By analyzing the GUS activity of DR5::GUS-transformed Arabidopsis seedlings, we showed that ABA, SA, salt, and cold treatments suppressed the auxin response. These findings suggest that other phytohormones and abiotic stress factors might alter endogenous auxin levels. Previous studies showed that GH3 genes regulate hormonal homeostasis. Our study indicated that some GH3 genes were significantly induced in M. sieversii after various phytohormone and abiotic stress treatments, and that ABA, SA, salt, and cold treatments reduce the endogenous level of axuin. Taken together, this study provides evidence that GH3 genes play important roles in the crosstalk between auxin, other phytohormones, and the abiotic stress response by maintaining auxin homeostasis.

GH dysfunction in Engrailed-2 knockout mice, a model for autism spectrum disorders

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Giovanni eProvenzano

2014-09-01

Full Text Available Insulin-like growth factor 1 (IGF-1 signaling promotes brain development and plasticity. Altered IGF-1 expression has been associated to autism spectrum disorders (ASD. IGF-1 levels were found increased in the blood and decreased in the cerebrospinal fluid of ASD children. Accordingly, IGF-1 treatment can rescue behavioral deficits in mouse models of ASD, and IGF-1 trials have been proposed for ASD children. IGF-1 is mainly synthesized in the liver, and its synthesis is dependent on growth hormone (GH produced in the pituitary gland. GH also modulates cognitive functions, and altered levels of GH have been detected in ASD patients.Here we analyzed the expression of GH, IGF-1, their receptors and regulatory hormones in the neuroendocrine system of adult male mice lacking the homeobox transcription factor Engrailed-2 (En2-/- mice. En2-/- mice display ASD-like behaviors (social interactions, defective spatial learning, increased seizure susceptibility accompanied by relevant neuropathological changes (loss of cerebellar and forebrain inhibitory neurons. Recent studies showed that En2 modulates IGF-1 activity during postnatal cerebellar development.We found that GH mRNA expression was markedly deregulated throughout the neuroendocrine axis in En2-/- mice, as compared to wild-type (WT controls. In mutant mice, GH mRNA levels were significantly increased in the pituitary gland, blood and liver, whereas decreased levels were detected in the hippocampus. These changes were paralleled by decreased levels of GH protein in the hippocampus but not other tissues of En2-/- mice. IGF-1 mRNA was significantly up-regulated in the liver and down-regulated in the En2-/- hippocampus, but no differences were detected in the levels of IGF-1 protein between the two genotypes. Our data strengthen the notion that altered GH levels in the hippocampus may be involved in learning disabilities associated to ASD.

Structural Basis for Prereceptor Modulation of Plant Hormones by GH3 Proteins

Energy Technology Data Exchange (ETDEWEB)

Westfall, Corey S.; Zubieta, Chloe; Herrmann, Jonathan; Kapp, Ulrike; Nanao, Max H.; Jez, Joseph M. (WU); (EMBL); (ESRF)

2013-04-08

Acyl acid amido synthetases of the GH3 family act as critical prereceptor modulators of plant hormone action; however, the molecular basis for their hormone selectivity is unclear. Here, we report the crystal structures of benzoate-specific Arabidopsis thaliana AtGH3.12/PBS3 and jasmonic acid-specific AtGH3.11/JAR1. These structures, combined with biochemical analysis, define features for the conjugation of amino acids to diverse acyl acid substrates and highlight the importance of conformational changes in the carboxyl-terminal domain for catalysis. We also identify residues forming the acyl acid binding site across the GH3 family and residues critical for amino acid recognition. Our results demonstrate how a highly adaptable three-dimensional scaffold is used for the evolution of promiscuous activity across an enzyme family for modulation of plant signaling molecules.

Examination of Growth Hormone (GH) Gene Polymorphism and its Association with Body Weight and Selected Body Dimensions in Ducks.

Science.gov (United States)

Mazurowski, Artur; Frieske, Anna; Kokoszynski, Dariusz; Mroczkowski, Sławomir; Bernacki, Zenon; Wilkanowska, Anna

2015-01-01

The main objective of the study was to assess the polymorphism in intron 2 of the GH gene and its association with some morphological traits (body weight--BW, length of trunk with neck--LTN, length of trunk--LT, chest girth--CG, length of breast bone--LBB, length of shank--LS). Polymorphism in intron 2 of the GH gene was evaluated for four duck populations (Pekin ducks AF51, Muscovy ducks from a CK and CRAMMLCFF mother and Mulard ducks). Genetic polymorphism was determined with the PCR-RFLP method using the BsmFI restriction enzyme. In the studied duck sample two alleles (GH(C) and GH(T)) and three genotypes (GH/TT, GH/CT, GH/CC) were found at locus GH/BsmFI. In both groups of Muscovies and in Mulards the dominant allele was GH(T). On the contrary in Pekin ducks AF51, the frequency of both alleles was found to be similar. The most frequent genotype in the examined ducks was GH/TT. In Pekin ducks AF51 three genotypes were observed, while in Mulard ducks and in male Muscovy ducks from a mother marked as CK, two genotypes (GH/TT and GH/CT) were identified. Muscovy duck females from a CK mother and all males and females of Muscovy duck from a CRAMMLCFF mother were monomorphic with only the GH/TTgenotype detected. The results showed that males of Pekin duck AF51 with the GH/TT genotype were characterized by higher (P ducks AF51, this same trend was observed; individuals with GH/TT genotype were superior (P ducks with the GH/TT genotype were distinguished by higher values of all evaluated traits compared to ducks with GH/CT and GH/CC genotypes, however most of the recorded differences were not significant. The only trait markedly impacted (P < 0.05) by the polymorphism of the GH gene intron 2 was the LS value in males.

Adult height after long-term, continuous growth hormone (GH) treatment in short children born small for gestational age: results of a randomized, double-blind, dose-response GH trial

NARCIS (Netherlands)

Y. van Pareren; M. Houdijk; M. Jansen (Maarten); M. Reeser; P.G.H. Mulder (Paul); A.C.S. Hokken-Koelega (Anita)

2003-01-01

textabstractThe GH dose-response effect of long-term continuous GH treatment on adult height (AH) was evaluated in 54 short children born small for gestational age (SGA) who were participating in a randomized, double-blind, dose-response trial. Patients were randomly and blindly

Psychometric properties of two measures of psychological well-being in adult growth hormone deficiency

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Russell-Jones David L

2006-03-01

Full Text Available Abstract Background Psychometric properties of two measures of psychological well-being were evaluated for adults with growth hormone deficiency (GHD: the General Well-being Index, (GWBI – British version of the Psychological General Well-being Index, and the 12-item Well-being Questionnaire (W-BQ12. Methods Reliability, structure and other aspects of validity were investigated in a cross-sectional study of 157 adults with treated or untreated GHD, and sensitivity to change in a randomised placebo-controlled study of three months' growth hormone (GH withdrawal from 12 of 21 GH-treated adults. Results Very high completion rates were evidence that both questionnaires were acceptable to respondents. Factor analyses did not indicate the existence of useful GWBI subscales, but confirmed the validity of calculating a GWBI Total score. However, very high internal consistency reliability (Cronbach's alpha = 0.96, N = 152, probably indicated some item redundancy in the 22-item GWBI. On the other hand, factor analyses confirmed the validity of the three W-BQ12 subscales of Negative Well-being, Energy, and Positive Well-being, each having excellent internal reliability (alphas of 0.86, 0.86 and 0.88, respectively, N from 152 to 154. There was no sign of item redundancy in the highly acceptable Cronbach's alpha of 0.93 (N = 148 for the whole W-BQ12 scale. Whilst neither questionnaire found significant differences between GH-treated and non-GH-treated patients, there were correlations (for GH-treated patients with duration of GH treatment for GWBI Total (r = -0.36, p = 0.001, N = 85, W-BQ12 Total (r = 0.35, p = 0.001, N = 88 and for all W-BQ12 subscales: thus the longer the duration of GH treatment (ranging from 0.5 to 10 years, the better the well-being. Both questionnaires found that men had significantly better overall well-being than women. The W-BQ12 was more sensitive to change than the GWBI in the GH-Withdrawal study. A significant between

Evolution of GH secretion in urine during an in-patient slimming course in obese children.

Science.gov (United States)

Lehingue, Y; Locard, E; Vivant, J F; Mounier, A; Serban, A; Remontet, L; Porquet, D; Joly, M O; Mamelle, N

2000-03-01

To estimate the change in GH excretion in urine (GH-U) during a slimming course, and if increased, to assess the components of the course related to the increase in obese children. Observational follow-up study of patients admitted for primary obesity to an in-patient slimming course lasting at least 10 weeks. 48 complete observations out of 54 consecutive pre-pubertal patients admitted to a paediatric centre for treatment of primary obesity (BMI greater than the 90th percentile of the national reference curves). GH excretion in urine by immunoradiometric assay, at entry and after 10 weeks, various anthropometric measurements, nutritional intake and departure from the prescribed diet, time spent in physical activity, sleep duration. A mean decrease of 0.90 standard deviations for BMI was accompanied by a 34% increase of GH-U. Time spent in physical activity was the only component of the course found to be related to the magnitude of GH-U increase. The results of this observational study confirm that GH-U is increased after a slimming course in children, and suggest that physical activity is a major contributor to the restoration of normal GH-U levels.

Baseline Body Composition in Prepubertal Short Stature Children with Severe and Moderate Growth Hormone Deficiency

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Pawel Matusik

2016-01-01

Full Text Available Objective. To compare body composition parameters in short children with severe versus moderate and no growth hormone deficiency (GHD. Design and Method. 61 children (40 boys were studied. Height SDS, BMI Z-score, waist/height ratio (W/HtR, and body composition parameters (BIA as fat tissue (FAT%, fat-free mass (FFM%, predicted muscle mass (PMM%, and total body water (TBW% were evaluated. GH secretion in the overnight profile and two stimulation tests and insulin-like growth factor 1 (IGF-1 level were measured. Results. Overall, in 16 (26% moderate (7.0 > peak GH < 10 ng/mL and in 11 (18% severe (GH ≤ 7.0 ng/mL GHD was diagnosed. In children with sGHD BMI Z-score, W/HtR and FAT% were significantly higher, while FFM%, PMM%, and TBW% were significantly lower versus mGHD and versus noGHD subgroups. No significant differences between mGHD and noGHD were found. There were no differences in height SDS and IGF-1 SDS between evaluated subgroups. Night GH peak level correlated significantly with FAT%, FFM%, PMM%, and TBW%, (p<0.05 in the entire group. Conclusions. Only sGHD is associated with significant impairment of body composition. Body composition analysis may be a useful tool in distinguishing between its severe and moderate form of GHD.

GH97 is a new family of glycoside hydrolases, which is related to the α-galactosidase superfamily

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Naumoff Daniil G

2005-08-01

Full Text Available Abstract Background As a rule, about 1% of genes in a given genome encode glycoside hydrolases and their homologues. On the basis of sequence similarity they have been grouped into more than ninety GH families during the last 15 years. The GH97 family has been established very recently and initially included only 18 bacterial proteins. However, the evolutionary relationship of the genes encoding proteins of this family remains unclear, as well as their distribution among main groups of the living organisms. Results The extensive search of the current databases allowed us to double the number of GH97 family proteins. Five subfamilies were distinguished on the basis of pairwise sequence comparison and phylogenetic analysis. Iterative sequence analysis revealed the relationship of the GH97 family with the GH27, GH31, and GH36 families of glycosidases, which belong to the α-galactosidase superfamily, as well as a more distant relationship with some other glycosidase families (GH13 and GH20. Conclusion The results of this study show an unexpected sequence similarity of GH97 family proteins with glycoside hydrolases from several other families, that have (β/α8-barrel fold of the catalytic domain and a retaining mechanism of the glycoside bond hydrolysis. These data suggest a common evolutionary origin of glycosidases representing different families and clans.

Prevalence of growth hormone deficiency in adult polytransfused β-thalassemia patients and correlation with transfusional and chelation parameters.

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Poggi, M; Pascucci, C; Monti, S; Pugliese, P; Lauri, C; Amodeo, G; Girelli, G; Toscano, V

2010-09-01

Dysfunction of GH-IGF-I axis has been described in many patients affected by β-thalassemia major (TM), especially in children and in adolescents. Recent studies have demonstrated the necessity to evaluate adult patients affected by TM to establish the presence of this alteration which could be relevant in the pathogenesis of cardiac and bone disease, frequently present in this hematological condition. The pathogenesis of this alteration, correlated in the past with iron overload, is not yet completely understood. The aim of this paper is to evaluate GH-IGF-I axis in a group of adult polytransfused β-thalassemic patients (TM) and to correlate the results with transfusional and chelation parameters. We performed an arginine plus GHRH stimulation test in 28 adult TM patients. Ferritin, IGF-I, liver enzymes, and liver iron concentration, assessed by a superconducting quantum interference device (SQUID) susceptometer were also determined. Moreover, in each patient we evaluated the bone status by a dual-energy X-ray absorptiometry study. We found the presence of GH deficit in 9 patients (32.1%). There were no significant differences between the two groups regarding the value of ferritin, liver enzymes, and liver iron concentration, assessed by SQUID. The group affected by GH deficit showed a worse bone profile. This study confirms the necessity to screen the status of GH/IGF-I axis in this group of patients, even in adult age. The presence of GH deficiency does not seem to be correlated with the efficacy parameters of transfusional and chelation therapy. Other mechanisms, additional to iron overload, could therefore play a role in the pathogenesis of this clinical condition. The presence of GH deficit seems to be very important on clinical aspects, like bone disease, that are crucial for quality of life in these patients.

GhWRKY68 reduces resistance to salt and drought in transgenic Nicotiana benthamiana.

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Haihong Jia

Full Text Available The WRKY transcription factors modulate numerous physiological processes, including plant growth, development and responses to various environmental stresses. Currently, our understanding of the functions of the majority of the WRKY family members and their possible roles in signalling crosstalk is limited. In particular, very few WRKYs have been identified and characterised from an economically important crop, cotton. In this study, we characterised a novel group IIc WRKY gene, GhWRKY68, which is induced by different abiotic stresses and multiple defence-related signalling molecules. The β-glucuronidase activity driven by the GhWRKY68 promoter was enhanced after exposure to drought, salt, abscisic acid (ABA and H2O2. The overexpression of GhWRKY68 in Nicotiana benthamiana reduced resistance to drought and salt and affected several physiological indices. GhWRKY68 may mediate salt and drought responses by modulating ABA content and enhancing the transcript levels of ABA-responsive genes. GhWRKY68-overexpressing plants exhibited reduced tolerance to oxidative stress after drought and salt stress treatments, which correlated with the accumulation of reactive oxygen species (ROS, reduced enzyme activities, elevated malondialdehyde (MDA content and altered ROS-related gene expression. These results indicate that GhWRKY68 is a transcription factor that responds to drought and salt stresses by regulating ABA signalling and modulating cellular ROS.

The effect of suppressor of cytokine signaling 3 on GH signaling in beta-cells

DEFF Research Database (Denmark)

Rønn, Sif G; Hansen, Johnny A; Lindberg, Karen

2002-01-01

GH is an important regulator of cell growth and metabolism. In the pancreas, GH stimulates mitogenesis as well as insulin production in beta-cells. The cellular effects of GH are exerted mainly through activation of the Janus kinase-signal transducer and activator of transcription (STAT) pathway...... stable transfection of the beta-cell lines with plasmids expressing SOCS-3 under the control of an inducible promoter, a time- and dose-dependent expression of SOCS-3 in the cells was obtained. EMSA showed that SOCS-3 is able to inhibit GH-induced DNA binding of both STAT3 and STAT5 in RIN-5AH cells...

A Novel Tool for Peptide Pattern Recognition Identifies 13 Subgroups of the GH61 Family

DEFF Research Database (Denmark)

Busk, Peter Kamp; Lange, Mette; Lange, Lene

2011-01-01

Proteins of the glycosyl hydrolase family 61 (gh61) are important proteins for fungal degradation of biomass. There are 132 entries for gh61 in the CAZY database, no subfamilies have been defined and each fungus may have several gh61s with very different sequences. Alignment of highly divergent s...

Substrate Metabolism and Insulin Sensitivity During Fasting in Obese Human Subjects: Impact of GH Blockade.

Science.gov (United States)

Pedersen, Morten Høgild; Svart, Mads Vandsted; Lebeck, Janne; Bidlingmaier, Martin; Stødkilde-Jørgensen, Hans; Pedersen, Steen Bønløkke; Møller, Niels; Jessen, Niels; Jørgensen, Jens O L

2017-04-01

Insulin resistance and metabolic inflexibility are features of obesity and are amplified by fasting. Growth hormone (GH) secretion increases during fasting and GH causes insulin resistance. To study the metabolic effects of GH blockade during fasting in obese subjects. Nine obese males were studied thrice in a randomized design: (1) after an overnight fast (control), (2) after 72 hour fasting (fasting), and (3) after 72 hour fasting with GH blockade (pegvisomant) [fasting plus GH antagonist (GHA)]. Each study day consisted of a 4-hour basal period followed by a 2-hour hyperinsulinemic, euglycemic clamp combined with indirect calorimetry, assessment of glucose and palmitate turnover, and muscle and fat biopsies. GH levels increased with fasting (P fasting-induced reduction of serum insulin-like growth factor I was enhanced by GHA (P Fasting increased lipolysis and lipid oxidation independent of GHA, but fasting plus GHA caused a more pronounced suppression of lipid intermediates in response to hyperinsulinemic, euglycemic clamp. Fasting-induced insulin resistance was abrogated by GHA (P Fasting plus GHA also caused elevated glycerol levels and reduced levels of counterregulatory hormones. Fasting significantly reduced the expression of antilipolytic signals in adipose tissue independent of GHA. Suppression of GH activity during fasting in obese subjects reverses insulin resistance and amplifies insulin-stimulated suppression of lipid intermediates, indicating that GH is an important regulator of substrate metabolism, insulin sensitivity, and metabolic flexibility also in obese subjects. Copyright © 2017 by the Endocrine Society

GH32 family activity: a topological approach through protein contact networks.

Science.gov (United States)

Cimini, Sara; Di Paola, Luisa; Giuliani, Alessandro; Ridolfi, Alessandra; De Gara, Laura

2016-11-01

The application of Protein Contact Networks methodology allowed to highlight a novel response of border region between the two domains to substrate binding. Glycoside hydrolases (GH) are enzymes that mainly hydrolyze the glycosidic bond between two carbohydrates or a carbohydrate and a non-carbohydrate moiety. These enzymes are involved in many fundamental and diverse biological processes in plants. We have focused on the GH32 family, including enzymes very similar in both sequence and structure, each having however clear specificities of substrate preferences and kinetic properties. Structural and topological differences among proteins of the GH32 family have been here identified by means of an emerging approach (Protein Contact network, PCN) based on the formalization of 3D structures as contact networks among amino-acid residues. The PCN approach proved successful in both reconstructing the already known functional domains and in identifying the structural counterpart of the properties of GH32 enzymes, which remain uncertain, like their allosteric character. The main outcome of the study was the discovery of the activation upon binding of the border (cleft) region between the two domains. This reveals the allosteric nature of the enzymatic activity for all the analyzed forms in the GH32 family, a character yet to be highlighted in biochemical studies. Furthermore, we have been able to recognize a topological signature (graph energy) of the different affinity of the enzymes towards small and large substrates.

The growth hormone (GH)-insulin-like growth factor axis during testosterone replacement therapy in GH-treated hypopituitary males

DEFF Research Database (Denmark)

Fisker, Sidse; Nørrelund, Helene; Juul, A

2001-01-01

in relation to two testosterone injections. Mean baseline IGF-I levels were 352 +/- 135 microg/L, and they remained unaltered during the study period (analysis of variance (ANOVA), P = 0.88). Free IGF-I levels did not change either (ANOVA, P = 0.35). Serum IGF binding protein-3 (IGFBP-3) and acid......-labile subunit decreased (ANOVA, P = 0.04 and P = 0.02 respectively) but post hoc analysis did not reveal a particular difference between days. IGFBP-1 increased following testosterone administration (ANOVA, P = 0.05), whereas GH binding protein levels tended to decrease following testosterone administration...... (ANOVA, P = 0.08). Prostate-specific antigen tended slightly to increase after each testosterone injection (ANOVA, P = 0.08, post hoc, NS). We conclude that major changes in total IGF-I are not induced during conventional intramuscular testosterone replacement in GH-treated hypopituitary males...

PROMIS GH (Patient-Reported Outcomes Measurement Information System Global Health) Scale in Stroke: A Validation Study.

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Katzan, Irene L; Lapin, Brittany

2018-01-01

The International Consortium for Health Outcomes Measurement recently included the 10-item PROMIS GH (Patient-Reported Outcomes Measurement Information System Global Health) scale as part of their recommended Standard Set of Stroke Outcome Measures. Before collection of PROMIS GH is broadly implemented, it is necessary to assess its performance in the stroke population. The objective of this study was to evaluate the psychometric properties of PROMIS GH in patients with ischemic stroke and intracerebral hemorrhage. PROMIS GH and 6 PROMIS domain scales measuring same/similar constructs were electronically collected on 1102 patients with ischemic and hemorrhagic strokes at various stages of recovery from their stroke who were seen in a cerebrovascular clinic from October 12, 2015, through June 2, 2017. Confirmatory factor analysis was performed to evaluate the adequacy of 2-factor structure of component scores. Test-retest reliability and convergent validity of PROMIS GH items and component scores were assessed. Discriminant validity and responsiveness were compared between PROMIS GH and PROMIS domain scales measuring the same or related constructs. Analyses were repeated stratified by stroke subtype and modified Rankin Scale score validity was good with significant correlations between all PROMIS GH items and PROMIS domain scales ( P 0.5) was demonstrated for 8 of the 10 PROMIS GH items. Reliability and validity remained consistent across stroke subtype and disability level (modified Rankin Scale, <2 versus ≥2). PROMIS GH exhibits acceptable performance in patients with stroke. Our findings support International Consortium for Health Outcomes Measurement recommendation to use PROMIS GH as part of the standard set of outcome measures in stroke. © 2017 American Heart Association, Inc.

High serum levels of growth hormone (GH) and insulin-like growth factor-I (IGF-I) during high-dose GH treatment in short children born small for gestational age

NARCIS (Netherlands)

M. van Dijk (Marije); P.G.H. Mulder (Paul); E.C.A.M. Houdijk (Mieke); J.C. Mulder (Jaap); K. Noordam (Kees); R.J.H. Odink (Roelof); C. Rongen-Westerlaken (Ciska); P.G. Voorhoeve (Paul); J.J.J. Waelkens (Johan); W.H. Stokvis-Brantsma; A.C.S. Hokken-Koelega (Anita)

2006-01-01

textabstractContext: Epidemiological studies have indicated that high serum levels of GH and IGF-I are associated with long-term risks. Objective: The objective of the study was to evaluate the changes in serum levels of GH during overnight profiles, IGF-I, and IGF binding protein 3 (IGFBP-3) in

European audit of current practice in diagnosis and treatment of childhood growth hormone deficiency

DEFF Research Database (Denmark)

Juul, Anders; Bernasconi, Sergio; Clayton, Peter E

2002-01-01

The present survey among members of the ESPE on current practice in diagnosis and treatment of growth hormone (GH) deficiency (GHD) is of great clinical relevance and importance in the light of the recently published guidelines for diagnosis and treatment of GHD by the Growth Hormone Research...... Society. We have found much conformity but also numerous discrepancies between the recommendations of the Growth Hormone Research Society and the current practice in Europe....

Effects of dietary genistein on GH/IGF-I axis of Nile tilapia Oreochromis niloticus

Science.gov (United States)

Chen, Dong; Wang, Wei; Ru, Shaoguo

2016-09-01

There is considerable concern that isoflavones, such as genistein in fish feed composed of soybean protein, aff ects somatic growth in fish. Our previous works demonstrated that 30 and 300 μg/g dietary genistein had no significant eff ect on growth performance in Nile tilapia ( Oreochromis niloticus), but the higher level of genistein (3 000 μg/g) significantly depressed growth. This study was conducted to further examine the eff ects of dietary genistein on the endocrine disruption on growth hormone/insulin-like growth factor-I (GH/IGF-I) axis in Nile tilapia ( O. niloticus). Juvenile fish were fed by hand twice daily to satiation with one of four isonitrogenous and isoenergetic diets, each containing either 0, 30, 300 or 3 000 μg/g genistein. Following an 8-week feeding period, plasma GH and IGF-I levels were investigated by radioimmunoassay and gene expression levels of gh, ghrelin, gnrhs, ghr, npy, npyrs, pacap, ghrs, i gf-I, igf-Ir, and igfbp3 were examined by real-time PCR. The results show that no significant change in plasma GH and IGF-I levels in fish fed with diets containing 30 μg/g and 300 μg/g genistein. mRNA expression of genes along the GH/IGF-I axis remained unaff ected, except for igf-Ir, which was stimulated by the 300 μg/g genistein diet. While in fish fed the 3 000 μg/g genistein diet, the plasma GH and IGF-I levels decreased, and mRNA expression of gh, ghr2, npyr1, igf-I, and igf-Ir were also significantly depressed. In contrast, npy and igfbp3 mRNA expression were enhanced. This study provides convincing evidence for growth impediment by genistein by disturbing the GH/IGF-I axis in Nile tilapia O. niloticus.

Effects of Growth Hormone on Bone.

Science.gov (United States)

Tritos, Nicholas A; Klibanski, Anne

2016-01-01

Describe the effects of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) on the skeleton. The GH and IGF-1 axis has pleiotropic effects on the skeleton throughout the lifespan by influencing bone formation and resorption. GH deficiency leads to decreased bone turnover, delayed statural growth in children, low bone mass, and increased fracture risk in adults. GH replacement improves adult stature in GH deficient children, increases bone mineral density (BMD) in adults, and helps to optimize peak bone acquisition in patients, during the transition from adolescence to adulthood, who have persistent GH deficiency. Observational studies suggest that GH replacement may mitigate the excessive fracture risk associated with GH deficiency. Acromegaly, a state of GH and IGF-1 excess, is associated with increased bone turnover and decreased BMD in the lumbar spine observed in some studies, particularly in patients with hypogonadism. In addition, patients with acromegaly appear to be at an increased risk of morphometric-vertebral fractures, especially in the presence of active disease or concurrent hypogonadism. GH therapy also has beneficial effects on statural growth in several conditions characterized by GH insensitivity, including chronic renal failure, Turner syndrome, Prader-Willi syndrome, postnatal growth delay in patients with intrauterine growth retardation who do not demonstrate catchup growth, idiopathic short stature, short stature homeobox-containing (SHOX) gene mutations, and Noonan syndrome. GH and IGF-1 have important roles in skeletal physiology, and GH has an important therapeutic role in both GH deficiency and insensitivity states. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of the increase in GH and IGF-1 and effectiveness in the treatment on Zacatecas population; Evaluacion del aumento en GH e IGF-1 y eficacia en el tratamiento en poblacion zacatecana

Energy Technology Data Exchange (ETDEWEB)

Gallegos F, P. I.; Badillo A, V., E-mail: perla_gf17@hotmail.com [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Laboratorio de Radioinmunoanalisis y Quimioluminiscencia, Cipres No. 10, Fracc. La Penuela, 98060 Zacatecas (Mexico)

2013-10-15

The acromegaly and gigantism are dysfunctions that are caused by hyper-secretion of growth hormone (GH) and of production in liver of growth factor similar to the insulin type 1 (IGF-1) mediated by the GH secretion. The secretor pituitary adenomas of GH are the main cause of the hyper-secretion. The acromegaly and gigantism are manifested respectively by acral alterations and extremities increase, and an excessive growth of the bones. Although a world prevalence of 40-60 cases by inhabitants million is registered, very few formal studies exist that confirm this number. According to the program Epiacro in Mexico is considered a prevalence of 13 cases by inhabitants million. In the Zacatecas State official statistical numbers are not had for these pathologies. Due to the few registrations that exist, or to the cases reported in Mexico, is necessary to evaluate patients with suspicion and with hyper-secretion diagnostic of GH, to contribute and/or to reinforce the health state and national statistics. In this work the GH and IGF-1 concentrations were measured on Zacatecas population to estimate the age range and sex with more probability of suffering this illness, and to evaluate the patients that have received some treatment to check their effectiveness verifying the GH and IGF-1 decrease and being able to obtain normal values. We register 26 patient cases with suspicion of GH hyper-secretion, of these 9 were affected by the illness. The hyper-secretion cases were presented with more frequency in half age adults, being affected in a same way as much men as women. To the end of the study only an affected patient concludes with the pharmacological treatment for the GH hyper-secretion control of a group of 5. (Author)

Quality of life in children and adolescents with growth hormone deficiency: association with growth hormone treatment.

Science.gov (United States)

Geisler, Alexandra; Lass, Nina; Reinsch, Nicole; Uysal, Yvonne; Singer, Viola; Ravens-Sieberer, Ulrike; Reinehr, Thomas

2012-01-01

Quality of life (QoL) as it is related with growth hormone deficiency (GHD) is a matter of controversy. We analyzed QoL in 95 children aged 8-18 years with isolated GHD (72% male) treated with growth hormone (GH). These children were compared to 190 age- and gender-matched healthy children with similar height [height children of normal stature (control group 2: CG2). QoL was measured by the KINDL® questionnaire referring to six domains (physical well-being, emotional well-being, self-esteem, family, friends, and school). QoL was significantly reduced in CG1 (effect-size 0.21) compared to CG2, while QoL was not significantly altered in children with GHD. In multiple linear regression analyses adjusted to age, gender, BMI, migration background, and socioeconomic status, decreasing height-SDS was associated with poorer QoL (especially emotional well-being), and treatment with GH was related significantly to better self-esteem. Increase of height-SDS in children treated with GH was associated positively with QoL and all its subscales except family and school. These findings suggest psychological consequences of short stature in children and an improvement of QoL in children treated with GH with the focus on self-esteem and emotional well-being. Copyright © 2012 S. Karger AG, Basel.

The absence of GH signaling affects the susceptibility to high-fat diet-induced hypothalamic inflammation in male mice

DEFF Research Database (Denmark)

Baquedano, Eva; Ruiz-Lopez, Ana M; Sustarsic, Elahu G

2014-01-01

GH is important in metabolic control, and mice with disruption of the gene encoding the GH receptor (GHR) and GH binding protein (GHR-/- mice) are dwarf with low serum IGF-1 and insulin levels, high GH levels, and increased longevity, despite their obesity and altered lipid and metabolic profiles...

EXPANSIÓN Y DIVERGENCIA DEL LOCUS GH ENTRE EL MONO ARAÑA Y EL CHIMPANCÉ

OpenAIRE

DE MENDOZA, AGNÈS; ESQUIVEL, DOLORES; MARTÍNEZ, IRMA; BARRERA, HUGO

2005-01-01

Para precisar la historia muy particular de la hormona del crecimiento (GH) en los primates, se describieron los loci GH del mono araña, un mono del Nuevo Mundo y del chimpancé, una especie cercana al humano. Al menos seis genes integran ambos loci GH: todos del tipo GH en el mono araña, y dos GHs y cuatro lactógenos placentarios (PLs) en el chimpancé. Las regiones intergénicas del locus del chimpancé presentan un tamaño mayor a las del mono araña. Este trabajo conf...

Cloning and characterization of a novel Gladiolus hybridus AFP family gene (GhAFP-like) related to corm dormancy

Energy Technology Data Exchange (ETDEWEB)

Wu, Jian; Seng, Shanshan [Beijing Key Laboratory of Development and Quality Control of Ornamental Crops, Department of Ornamental Horticulture and Landscape Architecture, China Agricultural University, Beijing 100193 (China); Carianopol, Carina [Department of Biological Sciences, University of Toronto, Toronto, Ontario (Canada); Sui, Juanjuan [College of Biology, Fuyang Normal College, Fuyang, Anhui (China); Yang, Qiuyan; Zhang, Fengqin; Jiang, Huiru [Beijing Key Laboratory of Development and Quality Control of Ornamental Crops, Department of Ornamental Horticulture and Landscape Architecture, China Agricultural University, Beijing 100193 (China); He, Junna, E-mail: hejunna@cau.edu.cn [Beijing Key Laboratory of Development and Quality Control of Ornamental Crops, Department of Ornamental Horticulture and Landscape Architecture, China Agricultural University, Beijing 100193 (China); Yi, Mingfang, E-mail: ymfang@cau.edu.cn [Beijing Key Laboratory of Development and Quality Control of Ornamental Crops, Department of Ornamental Horticulture and Landscape Architecture, China Agricultural University, Beijing 100193 (China)

2016-02-26

Abscisic acid (ABA) is an important phytohormone controlling seed dormancy. AFPs (ABA INSENSITIVE FIVE BINDING PROTEINS) are reported to be negative regulators of the ABA signaling pathway. The involvement of AFPs in dormant vegetative organs remains poorly understood. Here, we isolated and characterized a novel AFP family member from Gladiolus dormant cormels, GhAFP-like, containing three conserved domains of the AFP family. Quantitative PCR analysis revealed that GhAFP-like was expressed in dormant organs and its expression was down-regulated along with corm storage. GhAFP-like was verified to be a nuclear-localized protein. Overexpressing GhAFP-like in Arabidopsis thaliana not only showed weaker seed dormancy with insensitivity to ABA, but also changed the expression of some ABA related genes. In addition, a primary root elongation assay showed GhAFP-like may involve in auxin signaling response. The results in this study indicate that GhAFP-like acts as a negative regulator in ABA signaling and is related to dormancy. - Highlights: • GhAFP-like is expessed in dormant corm. • Overexpressing GhAFP-like showed early germination and insensitivity to ABA. • Overexpressing GhAFP-like changed ABI5 downstream genes expression.

Cloning and characterization of a novel Gladiolus hybridus AFP family gene (GhAFP-like) related to corm dormancy

International Nuclear Information System (INIS)

Wu, Jian; Seng, Shanshan; Carianopol, Carina; Sui, Juanjuan; Yang, Qiuyan; Zhang, Fengqin; Jiang, Huiru; He, Junna; Yi, Mingfang

2016-01-01

Abscisic acid (ABA) is an important phytohormone controlling seed dormancy. AFPs (ABA INSENSITIVE FIVE BINDING PROTEINS) are reported to be negative regulators of the ABA signaling pathway. The involvement of AFPs in dormant vegetative organs remains poorly understood. Here, we isolated and characterized a novel AFP family member from Gladiolus dormant cormels, GhAFP-like, containing three conserved domains of the AFP family. Quantitative PCR analysis revealed that GhAFP-like was expressed in dormant organs and its expression was down-regulated along with corm storage. GhAFP-like was verified to be a nuclear-localized protein. Overexpressing GhAFP-like in Arabidopsis thaliana not only showed weaker seed dormancy with insensitivity to ABA, but also changed the expression of some ABA related genes. In addition, a primary root elongation assay showed GhAFP-like may involve in auxin signaling response. The results in this study indicate that GhAFP-like acts as a negative regulator in ABA signaling and is related to dormancy. - Highlights: • GhAFP-like is expessed in dormant corm. • Overexpressing GhAFP-like showed early germination and insensitivity to ABA. • Overexpressing GhAFP-like changed ABI5 downstream genes expression.

Evaluation of left ventricular mass and function, lipid profile, and insulin resistance in Egyptian children with growth hormone deficiency: A single-center prospective case-control study

Directory of Open Access Journals (Sweden)

Kotb Abbass Metwalley

2013-01-01

Full Text Available Background: Growth hormone deficiency (GHD in adults is associated with a cluster of cardiovascular risk factors that may contribute to an increased mortality for cardiovascular disease. In children, relatively few studies have investigated the effect of GHD and replacement therapy on cardiac performance and metabolic abnormalities that may place them at a higher risk of cardiovascular disease (CVD at an early age. Aim: This study was aimed to assess the left ventricular function, lipid profile, and degree of insulin resistance in Egyptian children with GHD before and after 1 year of GH replacement therapy. Settings and Design: Prospective case-control study, single-center study. Materials and Methods: Thirty children with short stature due to GHD were studied in comparison to 20 healthy age- and sex-matched children. All subjects were subjected to history, clinical examination, auxological assessment, and echocardiography to assess the left ventricular function. Blood samples were collected for measuring IGF-1, lipid profile (Total, LDL, HDL cholesterol, triglyceride, and atherogenic index (AI, fasting blood sugar, and fasting insulin levels. In addition, basal and stimulated GH levels were measured in children with suspected GHD. Statistical Analysis Used: Student′s t-test was used for parametric data, and the Mann-Whitney U-test was used for non-parametric data. Results: Total, LDL cholesterol, triglyceride, AI, and insulin were significantly higher in children with GHD than in healthy controls at baseline. After 12 months of GH replacement therapy, total, LDL cholesterol, triglyceride, AI and insulin were significantly decreased, while homeostatic model assessment for insulin resistance index (HOMA-IR was significantly increased compared to both pre-treatment and control values. At baseline, the left ventricular mass (LVM and left ventricular mass index (LVMi were significantly lower in GHD children than in controls. After 12 months of GH

Profile of mecasermin for the long-term treatment of growth failure in children and adolescents with severe primary IGF-1 deficiency

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Danilo Fintini

2009-07-01

Full Text Available Danilo Fintini, Claudia Brufani, Marco CappaEndocrinology Unit, “Bambino Gesù” Children’s Hospital-IRCCS, Rome, ItalyAbstract: Growth hormone insensitivity syndrome (GHI or insulin-like growth factor-1 (IGF-1 deficiency (IGFD is characterized by deficit of IGF-1 production due to alteration of response of growth hormone (GH receptor to GH. This syndrome is due to mutation of GH receptor or IGF-1 gene and patients affected showed no response to GH therapy. The only treatment is recombinant IGF-1 (mecasermin, which has been available since 1986, but approved in the United States by the US Food and Drug Administration only in 2005 and in Europe by the European Medicines Agency in 2007. To date, few studies are available on long-term treatment with mecasermin in IGFD patients and some of them have a very small number of subjects. In this review we discuss briefly clinical features of severe primary IGFD, laboratory findings, and indications for treatment. Results of long-term therapy with rhIGF1 (mecasermin in patients affected by severe primary IGFD and possible side effects are explained.Keywords: mecasermin, therapy, Laron syndrome, IGF-1

Growth hormone deficiency after mild combat-related traumatic brain injury.

Science.gov (United States)

Ioachimescu, Adriana G; Hampstead, Benjamin M; Moore, Anna; Burgess, Elizabeth; Phillips, Lawrence S

2015-08-01

Traumatic brain injury (TBI) has been recognized as a cause of growth hormone deficiency (GHD) in civilians. However, comparable data are sparse in veterans who incurred TBI during combat. Our objective was to determine the prevalence of GHD in veterans with a history of combat-related TBI, and its association with cognitive and psychosocial dysfunction. Single center prospective study. Twenty male veterans with mild TBI incurred during combat 8-72 months prior to enrollment. GHD was defined by a GH peak emotional, and quality of life of the GHD Veterans were described using Cohen's d. Large effect sizes were considered meaningful. Mean age was 33.7 years (SD 7.8) and all subjects had normal thyroid hormone and cortisol levels. Five (25%) exhibited a subnormal response to glucagon. Sixteen participants (80%) provided sufficient effort for valid neuropsychological assessment (12 GH-sufficient, 4 GHD). There were large effect size differences in self-monitoring during memory testing (d = 1.46) and inhibitory control (d = 0.92), with worse performances in the GHD group. While fatigue and post-traumatic stress disorder were comparable, the GHD group reported more depression (d = 0.80) and lower quality of life (d = 0.64). Our study found a 25% prevalence of GHD in veterans with mild TBI as shown by glucagon stimulation. The neuropsychological findings raise the possibility that GHD has adverse effects on executive abilities and mood. Further studies are needed to determine whether GH replacement is an effective treatment in these patients.

Male bovine GH transgenic mice have decreased adiposity with an adipose depot-specific increase in immune cell populations.

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Benencia, Fabian; Harshman, Stephanie; Duran-Ortiz, Silvana; Lubbers, Ellen R; List, Edward O; Householder, Lara; Al-Naeeli, Mawadda; Liang, Xiaoyu; Welch, Lonnie; Kopchick, John J; Berryman, Darlene E

2015-05-01

White adipose tissue (WAT) is composed of mature adipocytes and a stromal vascular fraction (SVF), which contains a variety of cells, including immune cells that vary among the different WAT depots. Growth hormone (GH) impacts immune function and adiposity in an adipose depot-specific manner. However, its effects on WAT immune cell populations remain unstudied. Bovine GH transgenic (bGH) mice are commonly used to study the in vivo effects of GH. These giant mice have an excess of GH action, impaired glucose metabolism, decreased adiposity, increased lean mass, and a shortened lifespan. Therefore, the purpose of this study was to characterize the WAT depot-specific differences in immune cell populations in the presence of excess GH in vivo. Three WAT depots were assessed: inguinal (sc), epididymal (EPI), and mesenteric (MES). Subcutaneous and MES bGH WAT depots showed a significantly higher number of total SVF cells, yet only MES bGH WAT had higher leukocyte counts compared with control samples. By means of flow cytometry analysis of the SVF, we detected greater macrophage and regulatory T-cell infiltration in sc and MES bGH WAT depots compared with controls. However, no differences were observed in the EPI WAT depot. RNA-sequencing confirmed significant alterations in pathways related to T-cell infiltration and activation in the sc depot with fewer significant changes in the EPI bGH WAT depot. These findings collectively point to a previously unrecognized role for GH in influencing the distribution of WAT immune cell populations in a depot-specific manner.

Early growth hormone (GH) treatment promotes relevant motor functional improvement after severe frontal cortex lesion in adult rats.

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Heredia, Margarita; Fuente, A; Criado, J; Yajeya, J; Devesa, J; Riolobos, A S

2013-06-15

A number of studies, in animals and humans, describe the positive effects of the growth hormone (GH) treatment combined with rehabilitation on brain reparation after brain injury. We examined the effect of GH treatment and rehabilitation in adult rats with severe frontal motor cortex ablation. Thirty-five male rats were trained in the paw-reaching-for-food task and the preferred forelimb was recorded. Under anesthesia, the motor cortex contralateral to the preferred forelimb was aspirated or sham-operated. Animals were then treated with GH (0.15 mg/kg/day, s.c) or vehicle during 5 days, commencing immediately or 6 days post-lesion. Rehabilitation was applied at short- and long-term after GH treatment. Behavioral data were analized by ANOVA following Bonferroni post hoc test. After sacrifice, immunohistochemical detection of glial fibrillary acid protein (GFAP) and nestin were undertaken in the brain of all groups. Animal group treated with GH immediately after the lesion, but not any other group, showed a significant improvement of the motor impairment induced by the motor lesion, and their performances in the motor test were no different from sham-operated controls. GFAP immunolabeling and nestin immunoreactivity were observed in the perilesional area in all injured animals; nestin immunoreactivity was higher in GH-treated injured rats (mainly in animals GH-treated 6 days post-lesion). GFAP immunoreactivity was similar among injured rats. Interestingly, nestin re-expression was detected in the contralateral undamaged motor cortex only in GH-treated injured rats, being higher in animals GH-treated immediately after the lesion than in animals GH-treated 6 days post-lesion. Early GH treatment induces significant recovery of the motor impairment produced by frontal cortical ablation. GH effects include increased neurogenesis for reparation (perilesional area) and for increased brain plasticity (contralateral motor area). Copyright © 2013 Elsevier B.V. All rights

Evaluation of insulin-like growth factor-1 and insulin like growth factor binding protein-3 in diagnosis of growth hormone deficiency in short-stature children

International Nuclear Information System (INIS)

Ali, A.; Hashim, R.; Khan, F.A.; Sattar, A.; Ijaz, A.; Manzoor, S.M.; Younas, M.

2009-01-01

Growth Hormone Deficiency (GHD) is conventionally diagnosed and confirmed by diminished peak Growth Hormone (GH) levels to provocative testing. Serum Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) are under the influence of GH and reflect the spontaneous endogenous GH secretion. Owing to the absence of a circadian rhythm, it is possible to take individual measurements of IGF-1 and IGFBP-3 at any time of the day for evaluation of GH status instead of subjecting the individual to cumbersome provocative tests. Objectives of this study were to compare IGF-1 and IGFBP-3 assays with Exercise and L-Dopa stimulation tests in the diagnosis of growth hormone deficiency in short stature children using ITT as gold standard. Methods: This validation study was conducted at Department of Chemical Pathology and Endocrinology, AFIP, Rawalpindi, from November 2005 to October 2006. Fifty-two short stature children were included in the study. Basal samples for GH levels and simultaneous IGF-1 and IGFBP-3 measurements were obtained and afterwards all children were subjected to sequential exercise and LDopa stimulation tests. Insulin Tolerance Test (ITT) was performed one week later with all the necessary precautionary measures. On the basis of ITT results, children were divided into two groups, i.e., 31 growth hormone deficient and 21 Normal Variant Short Stature (NVSS). Results: The diagnostic value of exercise stimulation test remained highest with sensitivity 90.3%, specificity 76.0%, Positive Predictive Value (PPV) 84.84%, Negative Predictive Value (NPV) 84.2% and accuracy 84.6%. The conventional L-Dopa stimulation had sensitivity 96.7%, specificity 38.0%, PPV 69.7%, NPV 88.8 % and accuracy 73.0%. The serum IGF-1 and IGFBP-3 levels were positively correlated with post ITT peak GH levels (r= 0.527, r=0.464 respectively, both p<0.001). The diagnostic value of IGF-1 had sensitivity 83.87%, specificity 76.2%, PPV 83.87%, NPV 76.2% and

Endocrinologic complications of cranial irradiation. Complications endocriniennes de l'irradiation cranienne

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Brauner, R.; Rappaport, R. (Hopital des Enfants Malades 75 - Paris (FR))

1989-09-01

Cranial irradiation has become one of the leading causes of growth hormone (GH) deficiency. The risk and time of onset of GH deficiency depend mainly on the dose delivered to the hypothalamo-pituitary region: GH deficiency is infrequent after doses under 20 grays and nearly constant after doses above 45 grays. For a given dose, a younger age at the time of irradiation and administration of the dose over a shorter time period increase the risk of GH deficiency. GH secretion can be adequately evaluated using rapid stimulation tests and is usually well correlated with growth, except in patients with radiation-induced precocious puberty or growth delay due to radiation-induced cartilage lesions.

Endocrinologic complications of cranial irradiation

International Nuclear Information System (INIS)

Brauner, R.; Rappaport, R.

1990-01-01

Cranial irradiation has become one of the leading causes of growth hormone (GH) deficiency. The risk and time of onset of GH deficiency depend mainly on the dose delivered to the hypothalamo-pituitary region: GH deficiency is infrequent after doses under 20 grays and nearly constant after doses above 45 grays. For a given dose, a younger age at the time of irradiation and administration of the dose over a shorter time period increase the risk of GH deficiency. GH secretion can be adequately evaluated using rapid stimulation tests and is usually well correlated with growth, except in patients with radiation-induced precocious puberty or growth delay due to radiation-induced cartilage lesions [fr

Endocrinologic complications of cranial irradiation

International Nuclear Information System (INIS)

Brauner, R.; Rappaport, R.

1989-01-01

Cranial irradiation has become one of the leading causes of growth hormone (GH) deficiency. The risk and time of onset of GH deficiency depend mainly on the dose delivered to the hypothalamo-pituitary region: GH deficiency is infrequent after doses under 20 grays and nearly constant after doses above 45 grays. For a given dose, a younger age at the time of irradiation and administration of the dose over a shorter time period increase the risk of GH deficiency. GH secretion can be adequately evaluated using rapid stimulation tests and is usually well correlated with growth, except in patients with radiation-induced precocious puberty or growth delay due to radiation-induced cartilage lesions [fr

Does the GH/IGF-1 axis contribute to skeletal sexual dimorphism? Evidence from mouse studies.

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Liu, Zhongbo; Mohan, Subburaman; Yakar, Shoshana

2016-04-01

The contribution of the gonadotropic axis to skeletal sexual dimorphism (SSD) was clarified in recent years. Studies with animal models of estrogen receptor (ER) or androgen receptor (AR) null mice, as well as mice with bone cell-specific ablation of ER or AR, revealed that both hormones play major roles in skeletal acquisition, and that estrogen regulates skeletal accrual in both sexes. The growth hormone (GH) and its downstream effector, the insulin-like growth factor-1 (IGF-1) are also major determinants of peak bone mass during puberty and young adulthood, and play important roles in maintaining bone integrity during aging. A few studies in both humans and animal models suggest that in addition to the differences in sex steroid actions on bone, sex-specific effects of GH and IGF-1 play essential roles in SSD. However, the contributions of the somatotropic (GH/IGF-1) axis to SSD are controversial and data is difficult to interpret. GH/IGF-1 are pleotropic hormones that act in an endocrine and autocrine/paracrine fashion on multiple tissues, affecting body composition as well as metabolism. Thus, understanding the contribution of the somatotropic axis to SSD requires the use of mouse models that will differentiate between these two modes of action. Elucidation of the relative contribution of GH/IGF-1 axis to SSD is significant because GH is approved for the treatment of normal children with short stature and children with congenital growth disorders. Thus, if the GH/IGF-1 axis determines SSD, treatment with GH may be tailored according to sex. In the following review, we give an overview of the roles of sex steroids in determining SSD and how they may interact with the GH/IGF-1 axis in bone. We summarize several mouse models with impaired somatotropic axis and speculate on the possible contribution of that axis to SSD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ghrelin- and GH-induced insulin resistance: no association with retinol-binding protein-4

DEFF Research Database (Denmark)

Vestergaard, Esben Thyssen; Krag, Morten B; Poulsen, Morten M

2013-01-01

Supraphysiological levels of ghrelin and GH induce insulin resistance. Serum levels of retinol-binding protein-4 (RBP4) correlate inversely with insulin sensitivity in patients with type 2 diabetes. We aimed to determine whether ghrelin and GH affect RBP4 levels in human subjects....

GhNAC18 , a novel cotton ( Gossypium hirsutum L.) NAC gene, is ...

African Journals Online (AJOL)

GhNAC18 is a novel NAC gene that was isolated from cotton (Gossypium hirsutum L.). The full-length cDNA was 1511 bp including an open reading frame of 1260 bp in length and encodes a protein of 419 amino acids. With qRT-PCR analysis, GhNAC18 was downregulated during natural and dark-induced senescence, ...

A Gossypium hirsutum GDSL lipase/hydrolase gene (GhGLIP) appears to be involved in promoting seed growth in Arabidopsis.

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Ma, Rendi; Yuan, Hali; An, Jing; Hao, Xiaoyun; Li, Hongbin

2018-01-01

GDSL lipase (GLIP) plays a pivotal role in plant cell growth as a multifunctional hydrolytic enzyme. Herein, a cotton (Gossypium hirsutum L. cv Xuzhou 142) GDSL lipase gene (GhGLIP) was obtained from developing ovules and fibers. The GhGLIP cDNA contained an open reading frame (ORF) of 1,143 base pairs (bp) and encodes a putative polypeptide of 380 amino acid residues. Sequence alignment indicated that GhGLIP includes four enzyme catalytic amino acid residue sites of Ser (S), Gly (G), Asn (N) and His (H), located in four conserved blocks. Phylogenetic tree analysis showed that GhGLIP belongs to the typical class IV lipase family with potential functions in plant secondary metabolism. Subcellular distribution analysis demonstrated that GhGLIP localized to the nucleus, cytoplasm and plasma membrane. GhGLIP was expressed predominantly at 5-15 day post anthesis (dpa) in developing ovules and elongating fibers, measured as mRNA levels and enzyme activity. Ectopic overexpression of GhGLIP in Arabidopsis plants resulted in enhanced seed development, including length and fresh weight. Meanwhile, there was increased soluble sugar and protein storage in transgenic Arabidopsis plants, coupled with the promotion of lipase activity. Moreover, the expression of cotton GhGLIP is induced by ethylene (ETH) treatment in vitro. A 1,954-bp GhGLIP promoter was isolated and expressed high activity in driving green fluorescence protein (GFP) expression in tobacco leaves. Cis-acting element analysis of the GhGLIP promoter (pGhGLIP) indicated the presence of an ethylene-responsive element (ERE), and transgenic tobacco leaves with ectopic expression of pGhGLIP::GFP-GUS showed increased GUS activity after ETH treatment. In summary, these results suggest that GhGLIP is a functional enzyme involved in ovule and fiber development and performs significant roles in seed development.

Clinical and molecuar characterization of Brazilian patients with growth hormone gene deletions

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I.J.P. Arnhold

1998-04-01

Full Text Available Genomic DNA from 23 patients with isolated growth hormone (GH deficiency (12 males and 11 females: heights -4.9 ± 1.4 SDS was screened for GH gene deletions by restriction endonuclease analysis of polymerase chain reaction amplification products. Three unrelated patients had typical features of severe GH deficiency and deletions (6.7 kb in two and 7.6 kb in one of the GH gene. The two patients with 6.7-kb deletions developed growth-attenuating anti-GH antibodies whereas the patient with the 7.6-kb deletion continued to grow with GH replacement therapy. Our finding that 3/23 (~13% Brazilian subjects had GH gene deletions agrees with previous studies of severe isolated GH deficiency subjects in other populations. Two of three subjects (67% with deletions developed blocking antibodies despite administration of exogenous GH at low doses. Interestingly, only 1/10 of cases with affected relatives or parental consanguinity had GH-1 gene deletions

Etiology of growth hormone deficiency in children and adolescents

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Mitrović Katarina

2013-01-01

Full Text Available Introduction. Growth hormone deficiency (GHD can be isolated or associated with deficiency of other pituitary gland hormones. According to age at diagnosis, causes of GHD are divided into congenital or acquired, and according to etiology into recognized and unknown. Objective. We analyzed etiology and prevalence of GHD, demographic data at birth, age, body height (BH and bone age at diagnosis as well as the frequency of other pituitary hormone deficiencies. Methods. The study involved 164 patients (109 male. The main criterion for the diagnosis of GHD was inadequate response of GH after two stimulation tests. The patients were classified into three groups: idiopathic, congenital and acquired GHD. Results. Idiopathic GHD was confirmed in 57.9% of patients, congenital in 11.6% and acquired in 30.5%. The mean age at diagnosis of GHD was 10.1±4.5 years. The patients with congenital GHD had most severe growth retardation (-3.4±1.4 SDS, while the patients with idiopathic GHD showed most prominent bone delay (-3.6±2.3 SDS. The prevalence of multiple pituitary hormone deficiency was 56.1%, in the group with congenital GHD 73.7%, acquired GHD 54.0% and idiopathic GHD 53.7%. The frequency of thyrotropin deficiency ranged from 88.2-100%, of adrenocorticotrophin 57.1-68.8% and of gonadotrophins deficiency 57.1- 63.0%, while deficiency of antidiuretic hormone was 2.0-25.0%. Conclusion. Although regular BH measurements enable early recognition of growth retardation, patients’ mean age and degree of growth retardation indicate that GHD is still diagnosed relatively late. A high incidence of other pituitary hormone deficiencies requires a detailed investigation of the etiology of disorders and evaluation of all pituitary functions in each child with confirmed GHD.

Increased linear bone growth by GH in the absence of SOCS2 is independent of IGF-1.

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Dobie, Ross; Ahmed, Syed F; Staines, Katherine A; Pass, Chloe; Jasim, Seema; MacRae, Vicky E; Farquharson, Colin

2015-11-01

Growth hormone (GH) signaling is essential for postnatal linear bone growth, but the relative importance of GHs actions on the liver and/or growth plate cartilage remains unclear. The importance of liver derived insulin like-growth factor-1 (IGF-1) for endochondral growth has recently been challenged. Here, we investigate linear growth in Suppressor of Cytokine Signaling-2 (SOCS2) knockout mice, which have enhanced growth despite normal systemic GH/IGF-1 levels. Wild-type embryonic ex vivo metatarsals failed to exhibit increased linear growth in response to GH, but displayed increased Socs2 transcript levels (P growth over a 12 day period. Despite this increase, IGF-1 transcript and protein levels were not increased in response to GH. In accordance with these data, IGF-1 levels were unchanged in GH-challenged postnatal Socs2(-/-) conditioned medium despite metatarsals showing enhanced linear growth. Growth-plate Igf1 mRNA levels were not elevated in juvenile Socs2(-/-) mice. GH did however elevate IGF-binding protein 3 levels in conditioned medium from GH challenged metatarsals and this was more apparent in Socs2(-/-) metatarsals. GH did not enhance the growth of Socs2(-/-) metatarsals when the IGF receptor was inhibited, suggesting that IGF receptor mediated mechanisms are required. IGF-2 may be responsible as IGF-2 promoted metatarsal growth and Igf2 expression was elevated in Socs2(-/-) (but not WT) metatarsals in response to GH. These studies emphasise the critical importance of SOCS2 in regulating GHs ability to promote bone growth. Also, GH appears to act directly on the metatarsals of Socs2(-/-) mice, promoting growth via a mechanism that is independent of IGF-1. © 2014 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

GH receptor blocker administration and muscle-tendon collagen synthesis in humans

DEFF Research Database (Denmark)

Nielsen, Rie Harboe; Doessing, Simon; Goto, Kazushige

2011-01-01

The growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis stimulates collagen synthesis in tendon and skeletal muscle, but no studies have investigated the effect of reducing IGF-I on collagen synthesis in healthy humans.......The growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis stimulates collagen synthesis in tendon and skeletal muscle, but no studies have investigated the effect of reducing IGF-I on collagen synthesis in healthy humans....

Cerebral cortex hyperthyroidism of newborn mct8-deficient mice transiently suppressed by lat2 inactivation.

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Núñez, Bárbara; Martínez de Mena, Raquel; Obregon, Maria Jesus; Font-Llitjós, Mariona; Nunes, Virginia; Palacín, Manuel; Dumitrescu, Alexandra M; Morte, Beatriz; Bernal, Juan

2014-01-01

Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2) cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8), in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated Lat2-/-, and Mct8-/yLat2-/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As described previously the single Mct8 KO neonates had a transient increase of 3,5,3'-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3'-triiodothyronine concentration and Hr expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development.

Cerebral cortex hyperthyroidism of newborn mct8-deficient mice transiently suppressed by lat2 inactivation.

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Bárbara Núñez

Full Text Available Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2 cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8, in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated Lat2-/-, and Mct8-/yLat2-/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As described previously the single Mct8 KO neonates had a transient increase of 3,5,3'-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3'-triiodothyronine concentration and Hr expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development.

The glucagon test in the diagnosis of growth hormone deficiency in children with short stature younger than 6 years.

Science.gov (United States)

Secco, Andrea; di Iorgi, Natascia; Napoli, Flavia; Calandra, Erika; Ghezzi, Michele; Frassinetti, Costanza; Parodi, Stefano; Casini, Maria Rosaria; Lorini, Renata; Loche, Sandro; Maghnie, Mohamad

2009-11-01

Few studies have addressed the diagnostic role of the glucagon test in children with suspected GH deficiency (GHD). The objective of the study was to investigate the diagnostic value of the glucagon test as an alternative test to insulin tolerance test (ITT) and arginine in GHD children younger than 6 yr. This study was conducted in two pediatric endocrinology centers. Forty-eight children (median age 4.2 yr, median height -3.0 sd score) with GHD confirmed by a peak GH to ITT and arginine less than 10 microg/liter (median 4.7 and 3.4 microg/liter, respectively) underwent a glucagon stimulation test. Magnetic resonance imaging showed normal hypothalamic-pituitary anatomy in 24 children, isolated anterior pituitary hypoplasia in seven, and structural hypothalamic-pituitary abnormalities in 17. Median GH peak response to glucagon (13.5 microg/liter) was significantly higher than that observed after ITT and arginine (P short stature. Normative data for this test in young children need to be established before its use in clinical practice.

Evaluation of in vivo [corrected] biological activity of new agmatine analogs of growth hormone-releasing hormone (GH-RH)

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Bokser, L; Zarandi, M; Schally, A V

1990-01-01

The effects of agmatine analogs of growth hormone releasing hormone (GH-RH) were compared to GH-RH(1-29)-NH2 after intravenous (iv) and subcutaneous (sc) administration to pentobarbital-anesthetized male rats. After the iv injection, the analogs [desNH2-Tyr1,Ala15,Nle27] GH-RH(1-28)Agm (MZ-2-51); [desNH2-Tyr1,D-Lys12,Ala15,Nle27] GH-RH(1-28)Agm (MZ-2-57); [desNH2-Tyr1,Ala15,D-Lys21,Nle27] GH-RH(1-28)Agm (MZ-2-75) and [desNH2-Tyr1, D-Lys12,21, Ala15, Nle27] GH-RH(1-28)Agm (MZ-2-87) showed a potency equivalent to 4.4, 1.9, 1.07 and 1.03 times that of GH-RH (1-29)-NH2, respectively, at 5 min and 5.6, 1.8, 1.9 and 1.8 times higher, respectively, at 15 min. After sc administration, analogs MZ-2-51, MZ-2-57 and MZ-2-75 showed to be 34.3, 14.3 and 10.5 times more potent than the parent hormone at 15 min and 179.1, 88.9 and 45.0 times more active, respectively, at 30 min. In addition, MZ-2-51 had prolonged GH-releasing activity as compared to the standard. We also compared the activity of MZ-2-51 and MZ-2-57 with their homologous L-Arg and D-Arg analogs [desNH2-Tyr1,Ala15,Nle27] GH-RH(1-29)-NH2 (MZ-2-117), [des-NH2Tyr1,D-Lys12, Ala15, Nle27] GH-RH(1-29)NH2 (MZ-2-123) and [desNH2-Tyr1,D-Lys12,Ala15, Nle27,D-Arg29] GH-RH(1-29)NH2 (MZ-2-135) after intramuscular (im) injection. MZ-2-51 induced a somewhat greater GH release than MZ-2-117 at 15 min, both responses being larger than the controls (p less than 0.01) at 15 and 30 min. MZ-2-57, MZ-2-123 and MZ-2-135 given i.m. were able to stimulate GH release only at 15 minutes (p less than 0.05). Animals injected i.m. with MZ-2-51, but not with MZ-2-117, showed GH levels significantly higher than the control group (p less than 0.05) at 60 min. GH-RH(1-29)NH2 had low activity intramuscularly when tested at a dose of 2.5 micrograms. No toxic effects were observed after the iv administration of 1 mg/kg of Agm GH-RH analogs. These results indicate that our Agm analogs are active iv, sc and im and that the substitutions made in these

Leptin does not mediate short-term fasting-induced changes in growth hormone pulsatility but increases IGF-I in leptin deficiency states.

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Chan, Jean L; Williams, Catherine J; Raciti, Patricia; Blakeman, Jennifer; Kelesidis, Theodore; Kelesidis, Iosif; Johnson, Michael L; Thorner, Michael O; Mantzoros, Christos S

2008-07-01

States of acute and chronic energy deficit are characterized by increased GH secretion and decreased IGF-I levels. The objective of the study was to determine whether changes in levels of leptin, a key mediator of the adaptation to starvation, regulate the GH-IGF system during energy deficit. We studied 14 healthy normal-weight men and women during three conditions: baseline fed and 72-h fasting (to induce hypoleptinemia) with administration of placebo or recombinant methionyl human leptin (r-metHuLeptin) (to reverse the fasting associated hypoleptinemia). We also studied eight normal-weight women with exercise-induced chronic energy deficit and hypothalamic amenorrhea at baseline and during 2-3 months of r-metHuLeptin treatment. GH pulsatility, IGF levels, IGF and GH binding protein (GHBP) levels were measured. During short-term energy deficit, measures of GH pulsatility and disorderliness and levels of IGF binding protein (IGFBP)-1 increased, whereas leptin, insulin, IGF-I (total and free), IGFBP-4, IGFBP-6, and GHBP decreased; r-metHuLeptin administration blunted the starvation-associated decrease of IGF-I. In chronic energy deficit, total and free IGF-I, IGFBP-6, and GHBP levels were lower, compared with euleptinemic controls; r-metHuLeptin administration had no major effect on GH pulsatility after 2 wk but increased total IGF-I levels and tended to increase free IGF-I and IGFBP-3 after 1 month. The GH/IGF system changes associated with energy deficit are largely independent of leptin deficiency. During acute energy deficit, r-metHuLeptin administration in replacement doses blunts the starvation-induced decrease of IGF-I, but during chronic energy deficit, r-metHuLeptin administration increases IGF-I and tends to increase free IGF-I and IGFBP-3.

Cirugía transesfenoidal: primera opción de tratamiento para adenomas hipofisarios secretores de GH Transsphenoidal surgery: first treatment option for GH secreting hypophyseal adenomas

OpenAIRE

Omar López Arbolay; Justo Luis González González; Osmany Morales Sabina; Lorenzo Nedel Valdés

2004-01-01

La elevación de los niveles de hormona del crecimiento (GH) promueve el crecimiento grotesco de partes acras (acromegalia) o incremento de la talla (gigantismo) según la edad, así como trastornos metabólicos de relevancia biológica. La adenomectomía selectiva clasifica entre las modalidades de tratamiento. El objetivo del presente trabajo fue evaluar los resultados del tratamiento microquirúrgico por vía transeptoesfenoidal de los adenomas productores de GH en nuestro medio. Presentamos un es...

Puberty and Pubertal Growth in GH-treated SGA Children: Effects of 2 Years of GnRHa Versus No GnRHa.

Science.gov (United States)

van der Steen, Manouk; Lem, Annemieke J; van der Kaay, Danielle C M; Hokken-Koèelega, Anita C S

2016-05-01

Most studies on puberty in children born small for gestational age (SGA) report height and age at onset of puberty. GH-treated SGA children with an adult height (AH) expectation below -2.5 SDS at onset of puberty can benefit from an additional 2 years of GnRH analog (GnRHa) treatment. There are no data on puberty and growth after discontinuation of GnRHa treatment in GH-treated SGA children. This study aimed to investigate the effects on puberty and pubertal growth of 2 years GnRHa vs no GnRHa in GH-treated SGA children. This was a GH trial involving 76 prepubertal short SGA children (36 girls) treated with GH. Thirty-two children received additional GnRHa for 2 years. Pubertal stages were 3-monthly assessed according to Tanner. Age, bone age, and median height at pubertal onset were lower in girls and boys in the GH/GnRHa group compared with the GH group. In girls and boys treated with GH/GnRHa, pubertal duration after stop of GnRHa treatment was shorter than pubertal duration in those with GH only (40.9 vs 46.7 mo; P = .044; 50.8 vs 57.5 months; P = .006; respectively). Height gain from onset of puberty until AH, including height gain during 2 years of GnRHa treatment, was 25.4 cm in girls and 33.0 cm in boys, which was 6.6 cm more than girls and boys treated with GH only. AH was similar in children treated with GH/GnRHa compared with those with GH only. GH-treated SGA children who start puberty with an AH expectation below -2.5 SDS and are treated with 2 years of GnRHa have a shorter pubertal duration after discontinuation of GnRHa compared with pubertal duration in children treated with GH only. Height gain from onset of puberty until AH is, however, more due to adequate growth during 2 years of GnRHa treatment resulting in a similar AH as children treated with GH only.

Delayed release formulation of the somatostatin analog RC-160 inhibits the growth hormone (GH) response to GH-releasing factor-(1-29)NH2 and decreases elevated prolactin levels in rats.

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Bokser, L; Schally, A V

1988-10-01

Recently, we have developed a long-acting delivery system for our somatostatin (SS) analog RC-160 based on injectable microcapsules in poly-(D,L-lactide-coglycolide). We studied the capacity of this formulation to repeatedly block the GH secretion induced by administration of GRF-(1-29)NH2 (GRF) on different days. Male rats anesthetized with pentobarbital were injected iv with 2.5 micrograms/kg BW GRF-(1-29)NH2 or saline. Five minutes later, blood samples were taken for GH measurement, and the animals were injected im with RC-160 microcapsules at a dose calculated to release 25 micrograms/day of the analog for 7 days or with the vehicle. The GRF stimuli were repeated 48 h, 96 h, and 8 days after administration of SS analog in microcapsules. GRF administration increased GH levels at the four times tested (P less than 0.01) in the control group injected with vehicle, while RC-160 microcapsules inhibited the GH response for more than 96 h (P less than 0.01). The GH levels augmented by pentobarbital were also decreased by the RC-160 microcapsules (P less than 0.01). Animals treated with microcapsules showed smaller increases in their body weight than untreated rats (P less than 0.05). We also investigated the effect of RC-160 microcapsules on hyperprolactinemic female rats implanted with pituitary glands under the kidney capsules. High PRL levels in rats bearing pituitary grafts showed a significant decrease when measured 4 days after the administration of RC-160 microcapsules. These results demonstrate the efficacy of the long-acting delivery system of the SS analog RC-160 and suggest the possible clinical usefulness of this formulation for lowering GH and PRL levels.

Histamine-induced paradoxical GH response to TRH/GnRH in men and women: dependence on gonadal steroid hormones

DEFF Research Database (Denmark)

Knigge, U; Thuesen, B; Dejgaard, A

1990-01-01

.025), but not during the early follicular phase of the cycle (GH peak: 1.7 +/- 0.5 vs 1.6 +/- 0.3 micrograms/l). In luteal-phase women the GH response to TRH/GnRH correlated with the serum estradiol-17 beta level (GH area/E2: r = 0.98; p less than 0.005) and the serum estrone level (GH area/E1: r = 0.81; p less than 0...

Glycoside Hydrolase (GH) 45 and 5 Candidate Cellulases in Aphelenchoides besseyi Isolated from Bird?s-Nest Fern

OpenAIRE

Wu, Guan-Long; Kuo, Tzu-Hao; Tsay, Tung-Tsuan; Tsai, Isheng J.; Chen, Peichen J.

2016-01-01

Five Aphelenchoides besseyi isolates collected from bird's-nest ferns or rice possess different parasitic capacities in bird's-nest fern. Two different glycoside hydrolase (GH) 45 genes were identified in the fern isolates, and only one was found in the rice isolates. A Abe GH5-1 gene containing an SCP-like family domain was found only in the fern isolates. Abe GH5-1 gene has five introns suggesting a eukaryotic origin. A maximum likelihood phylogeny revealed that Abe GH5-1 is part of the nem...

GH and cortisol responses following an acute session of respiratory muscle endurance training in severely obese patients.

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Sartorio, A; Agosti, F; Patrizi, A; Gattico, A; Tringali, G; Giunta, M; Muller, E E; Rigamonti, A E

2013-03-01

It is well established that obese patients are hypo-responsive to classical GH-releasing stimuli, including aerobic exercise. Recently, we have demonstrated that whole body vibration was able to markedly stimulate GH secretion in obese patients, thus suggesting that this refractoriness is not absolute but dependent on the GH-releasing stimulus. Furthermore, we have shown the ability of a respiratory muscle endurance training (RMET) to stimulate GH and cortisol secretion in healthy subjects. The objective of this study was to evaluate the effects of RMET on GH and cortisol responses in severely obese patients. Eight severely obese patients (4 M/4 F, mean age±SEM: 22.8±1.6 years, body mass index, BMI: 39.9±1.1 kg/m2) underwent an incremental progressive RMET protocol of 11 daily sessions, obtained through the use of a specifically designed respiratory device (Spiro Tiger®). The 12th session of RMET (15 min duration: 1 min at a respiration rate of 28 acts/min, 5 min at 32 acts/min, 5 min at 34 acts/min, 4 min at 36 acts/min) was associated with blood samplings for determination of GH, cortisol, and lactate (LA) levels. An age- and sex-matched normal-weighted control group (n=7, 4 M/3 F, age: 26.1±3.1 years, BMI: 22.4±0.6 kg/m2) was also recruited. In both normal-weighted subjects and obese patients, GH secretion significantly increased after a 15-min RMET session. Although serum GH levels at 30 min were higher in normal-weighted subjects than in obese patients, there was no statistically significant difference in either GH peaks or net GH areas under the curve between the 2 groups. RMET significantly increased serum cortisol levels in normal-weighted subjects, but was associated to a progressive cortisol decline in obese patients. RMET stimulated LA production, with no significant differences in normal-weighted subjects and in obese patients. A 15-min RMET session was capable to induce a GH response in severely obese patients, which was comparable to that

Urine metabonomic profiling of a female adolescent with PIT-1 mutation before and during growth hormone therapy: insights into the metabolic effects of growth hormone.

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Abd Rahman, Shaffinaz; Schirra, Horst Joachim; Lichanska, Agnieszka M; Huynh, Tony; Leong, Gary M

2013-01-01

Growth hormone (GH) is a protein hormone with important roles in growth and metabolism. The objective of this study was to investigate the metabolism of a human subject with severe GH deficiency (GHD) due to a PIT-1 gene mutation and the metabolic effects of GH therapy using Nuclear Magnetic Resonance (NMR)-based metabonomics. NMR-based metabonomics is a platform that allows the metabolic profile of biological fluids such as urine to be recorded, and any alterations in the profile modulated by GH can potentially be detected. Urine samples were collected from a female subject with severe GHD before, during and after GH therapy, and from healthy age- and sex-matched controls and analysed with NMR-based metabonomics. The samples were collected at a hospital and the study was performed at a research facility. We studied a 17 year old female adolescent with severe GHD secondary to PIT-1 gene mutation who had reached final adult height and who had ceased GH therapy for over 3 years. The subject was subsequently followed for 5 years with and without GH therapy. Twelve healthy age-matched female subjects acted as control subjects. The GH-deficient subject re-commenced GH therapy at a dose of 1 mg/day to normalise serum IGF-1 levels. Urine metabolic profiles were recorded using NMR spectroscopy and analysed with multivariate statistics to distinguish the profiles at different time points and identify significant metabolites affected by GH therapy. NMR-based metabonomics revealed that the metabolic profile of the GH-deficient subject altered with GH therapy and that her profile was different from healthy controls before, and during withdrawal of GH therapy. This study illustrates the potential use of NMR-based metabonomics for monitoring the effects of GH therapy on metabolism by profiling the urine of GH-deficient subjects. Further controlled studies in larger numbers of GH-deficient subjects are required to determine the clinical benefits of NMR-based metabonomics in

Análise molecular dos genes PROP1 e HESX1 em pacientes com displasia septo-ótica e/ou deficiência hormonal hipofisária

OpenAIRE

Cruz, Juliana B. [UNESP; Nunes, Vânia dos Santos [UNESP; Clara, Sueli A. [UNESP; Perone, Denise [UNESP; Kopp, Peter; Nogueira, Célia Regina [UNESP

2010-01-01

Objective: The present study aimed at evaluating the PROP1 and HESX1 genes in a group of patients with septo-optic dysplasia (SOD) and pituitary hormone deficiency (combined – CPHD; isolated GH deficiency – GHD). Eleven patients with a clinical and biochemical presentation consistent with CPHD, GHD or SOD were evaluated. Subjects and methods: In all patients, the HESX1 gene was analyzed by direct sequence analysis and in cases of CPHD the PROP1 gene was also sequenced. Results: A polymorphism...

A novel CLCN5 mutation in a boy with Bartter-like syndrome and partial growth hormone deficiency.

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Bogdanović, Radovan; Draaken, Markus; Toromanović, Alma; Dordević, Maja; Stajić, Natasa; Ludwig, Michael

2010-11-01

Dent disease is an X-linked recessive disorder affecting the proximal tubule and is characterized by low-molecular-weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis/nephrolithiasis with a variable number of features of Fanconi syndrome. It is most often associated with mutations in CLCN5, which encodes the endosomal electrogenic chloride/proton exchanger ClC-5. Renal acidification abnormalities are only rarely seen in Dent disease, whereas the hypokalemic metabolic alkalosis associated with hyperreninemic hyperaldosteronism (Bartter-like syndrome) has been reported in only one patient so far. We report on a 5-year-old boy with Dent disease caused by mutation in CLCN5 gene, c.1073G>A, who presented with hypokalemic metabolic alkalosis and hyperreninemic hyperaldosteronism persisting over the entire follow-up. No mutations were found in NKCC2, ROMK, NCCT, or ClC-Kb genes. In addition, the patient exhibited growth failure associated with partial growth hormone (GH) deficiency. Coexistence of Bartter-like syndrome features with LMWP should prompt a clinician to search for Dent disease. The Bartter syndrome phenotype seen in Dent disease patients may represent a distinct form of Bartter syndrome, the exact mechanism of which has yet to be fully elucidated. Growth delay that persists in spite of appropriate therapy should raise suspicion of other causes, such as GH deficiency.

"Micromegaly": an update on the prevalence of acromegaly with apparently normal GH secretion in the modern era.

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Butz, Laura B; Sullivan, Stephen E; Chandler, William F; Barkan, Ariel L

2016-12-01

Approximately 25 % of cases of clinically active acromegaly cases treated in our academic center between 1996 and 2000, were diagnosed in patients who had elevated plasma IGF-1 levels, but apparently "normal" 24-h mean plasma GH levels. The current study served to update the data for patients with acromegaly referred to our facility, after increasing awareness of this "normal" GH subpopulation throughout the medical community. A retrospective chart review was conducted on 157 patients with acromegaly who underwent resection of a confirmed somatotroph pituitary adenoma at the University of Michigan Health System between the dates of 1 Jan 2001 to 23 Sept 2015. Overall prevalence of acromegalic patients with "normal" GH levels, defined as GH 2 cm in the maximal diameter were encountered more frequently in the group with elevated GH (43 vs. 14 %, p acromegaly have "normal" GH, and therefore strengthens the growing body of evidence which supports the leading role of IGF-1 levels in diagnostic evaluation. At the present time, questions about the natural course of "micromegaly" and treatment benefits compared to the subpopulation with elevated GH levels remain unanswered, but research continues to build on our understanding of the heterogeneous population of individuals.

Reported shoes size during GH therapy: is foot overgrowth a myth or reality?

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Lago, Débora C F; Coutinho, Cláudia A; Kochi, Cristiane; Longui, Carlos A

2015-10-01

To describe population reference values for shoes size, and to identify possible disproportional foot growth during GH therapy. Construction of percentile chart based on 3,651 controls (male: 1,838; female: 1,813). The GH treated group included 13 children with idiopathic short stature (ISS) and 50 children with normal height, but with height prediction below their target height; male: 26 and female: 37 mean ± SD age 13.3 ± 1.9 and 12.9 ± 1.5 years, respectively. GH (0.05 mg/kg/day) was used for 3.2 ± 1.6 years, ranging from 1.0-10.3 years. Height expressed as SDS, target height (TH) SDS, self-reported shoes size and target shoes size (TSS) SDS were recorded. Reference values were established showed as a foot SDS calculator available online at www.clinicalcaselearning.com/v2. Definitive shoes size was attained in controls at mean age of 13y in girls and 14y in boys (average values 37 and 40, respectively). In the study group, shoes size was -0.15 ± 0.9 and -0.02 ± 1.3 SDS, with target feet of 0.08 ± 0.8 and -0.27 ± 0.7 SDS in males and females, respectively. There was a significant positive correlation between shoes size and familial TSS, between shoes size and height and between TSS and TH. There was no correlation between duration of GH treatment and shoes size. Our data suggest that during long-term treatment with GH, patients maintain proportional growth in shoes size and height, and the expected correlation with the familial target. We conclude that there is no excessive increase in the size of foot as estimated by the size of shoes in individuals under long term GH therapy.

Cirugía transesfenoidal: primera opción de tratamiento para adenomas hipofisarios secretores de GH Transsphenoidal surgery: first treatment option for GH secreting hypophyseal adenomas

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Omar López Arbolay

2004-12-01

Full Text Available La elevación de los niveles de hormona del crecimiento (GH promueve el crecimiento grotesco de partes acras (acromegalia o incremento de la talla (gigantismo según la edad, así como trastornos metabólicos de relevancia biológica. La adenomectomía selectiva clasifica entre las modalidades de tratamiento. El objetivo del presente trabajo fue evaluar los resultados del tratamiento microquirúrgico por vía transeptoesfenoidal de los adenomas productores de GH en nuestro medio. Presentamos un estudio retrospectivo de pacientes intervenidos por vía transeptoesfenoidal, por esta variedad de adenomas, en el servicio de neurocirugía del Hospital "Hermanos Ameijeiras" desde 1996 al 2003. Se analizaron edad, sexo, síntomas cardinales, imaginología, niveles hormonales, complicaciones y evolución posoperatoria. Resultó que las complicaciones relacionadas con el proceder quirúrgico no fueron relevantes y ninguna persistió más allá del mes. La diabetes insípida fue la más frecuente. Los síntomas mejoraron y los títulos de GH descendieron por debajo de los niveles de curación en el 58,06 % de los operados. Se concluye que la adenomectomía transeptoesfenoidal es un proceder seguro y recomendable como tratamiento de elección en estos pacientes.The elevation of the growth hormone (GH levels enhances the grotesque growth of acral parts (acromegaly or the increase of height (gigantism according to age, as well as metabolic disorders of biological relevance. The selective adenotomy is among the treatment modalities. The objective of the present paper was to evaluate the results of the microsurgical transseptosphenoidal treatment of the GH producing adenomas in our setting. A retrospective study of patients that underwent transseptosphenoidal surgery for presenting this variety of adenomas at the neurosurgery service of "Hermanos Ameijeiras" Hospital from 1996 to 2003, was conducted. Age, cardinal symptoms, imaging, hormonal levels

Insulin and GH secretion in adolescent girls with irregular cycles: polycystic vs multifollicular ovaries.

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Villa, P; Rossodivita, A; Fulghesu, A M; Cucinelli, F; Barini, A; Apa, R; Belosi, C; Lanzone, A

2003-04-01

In the present study insulin (I) and GH secretion was studied in a group of twenty-five young adolescent girls (mean age: 15 +/- 0.23 yr) with cycle irregularity associated to clinical signs of hyperandrogenism in comparison with that observed in eleven normal matched subjects with regular menses. All patients underwent basal hormone measurements and, on two consecutive days, an oral glucose tolerance test (OGTT) and a GHRH iv test. Therefore, all subjects had a transabdominal US scan for the measurement of ovarian volume and the characterization of ovarian morphology. On the basis of the US examination we found patients with polycystic ovaries (PCO-like group) and subjects with multifollicular ovaries (MFO group). PCO-like group exhibited T (pirregular menses showed plasma concentrations of AUC for I (AUC-I) significantly higher in respect to control group (7359.4 +/- 709 vs 5447 +/- 431 microIU/ml x 180 min, p<0.01) as well as both PCO-like group and MFO group did (p<0.001 and p<0.01) respectively. MFO group showed higher values of the AUC for GH (AUC-GH) (2809 +/- 432 ng/ml x 120 min) in respect to controls (1708 +/- 208 ng/ml x 120 min, p<0.05) and PCO-like subjects (p<0.001), who on the contrary showed the lowest AUC-GH values (618 +/- 119 ng/ml x 120 min). In conclusion, PCO-like patients associated hyperinsulinemia with a blunted GH secretion while MFO patients had higher GH secretion associated with higher AUC-I values in a way suggesting an immature and still developing reproductive system.

Chitinase family GH18: evolutionary insights from the genomic history of a diverse protein family

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Aronson Nathan N

2007-06-01

Full Text Available Abstract Background Chitinases (EC.3.2.1.14 hydrolyze the β-1,4-linkages in chitin, an abundant N-acetyl-β-D-glucosamine polysaccharide that is a structural component of protective biological matrices such as insect exoskeletons and fungal cell walls. The glycoside hydrolase 18 (GH18 family of chitinases is an ancient gene family widely expressed in archea, prokaryotes and eukaryotes. Mammals are not known to synthesize chitin or metabolize it as a nutrient, yet the human genome encodes eight GH18 family members. Some GH18 proteins lack an essential catalytic glutamic acid and are likely to act as lectins rather than as enzymes. This study used comparative genomic analysis to address the evolutionary history of the GH18 multiprotein family, from early eukaryotes to mammals, in an effort to understand the forces that shaped the human genome content of chitinase related proteins. Results Gene duplication and loss according to a birth-and-death model of evolution is a feature of the evolutionary history of the GH18 family. The current human family likely originated from ancient genes present at the time of the bilaterian expansion (approx. 550 mya. The family expanded in the chitinous protostomes C. elegans and D. melanogaster, declined in early deuterostomes as chitin synthesis disappeared, and expanded again in late deuterostomes with a significant increase in gene number after the avian/mammalian split. Conclusion This comprehensive genomic study of animal GH18 proteins reveals three major phylogenetic groups in the family: chitobiases, chitinases/chitolectins, and stabilin-1 interacting chitolectins. Only the chitinase/chitolectin group is associated with expansion in late deuterostomes. Finding that the human GH18 gene family is closely linked to the human major histocompatibility complex paralogon on chromosome 1, together with the recent association of GH18 chitinase activity with Th2 cell inflammation, suggests that its late expansion

Usefulness of magnetic resonance findings of the hypothalamic-pituitary region in the management of short children with growth hormone deficiency: evidence from a longitudinal study.

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Kalina, Maria A; Kalina-Faska, Barbara; Gruszczyńska, Katarzyna; Baron, Jan; Małecka-Tendera, Ewa

2012-01-01

The purpose of this study is to assess the relationship between magnetic resonance images (MRI) of the hypothalamic-pituitary (H-P) region and response to recombinant human growth hormone (rhGH) treatment in short children with growth hormone deficiency, basing on changes of auxologic parameters, as well as to answer the question if MRI may serve for selecting and monitoring the rhGH responders. The study group comprised 85 children treated with rhGH, aged 7.3-18.7 years, followed for the mean period of 3.2 years (range, 2.1-9.5 years). Auxologic parameters (height deficit hSDS, deviation from the mid-parental height hSDS-mpSDS, bone delay index bone age/chronological age ratio (BA/CA)) were assessed before, during and at the end of rhGH treatment; growth velocity was calculated before and during rhGH therapy. Parameters were correlated with the MRI of the H-P region. Structural anomalies of the H-P region were found in 22 (25.9%) children: empty sella syndrome (ESS) in 12 (14.1%) patients, ectopic posterior pituitary (EPP) in ten (11.8%). Patients' height deficit and their deviation from parental height before rhGH therapy was significantly greater in the EPP group (median hSDS = -3.8; hSDS-mpSDS = -2.5), bone age delay was the greatest in the ESS group (median BA/CA = 0.69), after therapy - in the EPP group (median BA/CA = 0.82). Growth velocity improved in the first year of the rhGH therapy in all groups; however, the most significant acceleration was observed in the EPP group (median delta hSDS = 0.9), then stabilised and was comparable in all groups. MRI may be helpful in predicting response to the rhGH treatment, providing midline abnormalities are taken into account.

A study on the serum growth hormone (GH) and insulin levels in patients with coronary heart disease

International Nuclear Information System (INIS)

Zhang Zhiwei; Ji Naijun; Mei Yibin; Chen Donghai; Tong Lijun; Fan Bifu; Wang Chengyao; Li Fuyuan

2005-01-01

Objective: To explore the clinical significance of the changes of serum growth hormone (GH) and insulin (IS) levels in patients with coronary heart disease (CHD). Methods: Serum GH and IS levels were determined with RIA in 120 patients with CHD and 50 controls. Results: The serum levels of GH in patients with CHD (127.16 ± 37.9 pmol/L) were significantly lower than those in controls (152.0 ± 41.2 pmol/L) (t=3.819, P 0.05). In patients complicated with heart failure, the serum GH levels were significantly lower than those in patients without heart failure (P 0.05). The serum IS levels were significantly higher in patients developing myocardial infarction than those in patients without this complication (P 0.05). In the patients succumbed in the hospital, both serum GH and IS levels were significantly lower than those in the patients finally recovered (P<0.05). Conclusion: In this study, serum GH levels were much lower in CHD patients. Whatever explanation of this finding is at best speculative and further study is mandatory. (authors)

GH3::GUS reflects cell-specific developmental patterns and stress-induced changes in wood anatomy in the poplar stem.

Science.gov (United States)

Teichmann, Thomas; Bolu-Arianto, Waode Hamsinah; Olbrich, Andrea; Langenfeld-Heyser, Rosemarie; Göbel, Cornelia; Grzeganek, Peter; Feussner, Ivo; Hänsch, Robert; Polle, Andrea

2008-09-01

GH3 genes related to the auxin-inducible Glycine max (L.) Merr. GmGH3 gene encode enzymes that conjugate amino acids to auxin. To investigate the role of GH3 enzymes in stress responses and normal wood development, Populus x canescens (Ait.) was transformed with the promoter-reporter construct GH3::GUS containing a GH3 promoter and the 5' UTR from soybean. beta-Glucuronidase (GUS) activity was present in the vascular tissues of leaves and in developing lateral roots and was inducible in silent tissues by external auxin application. A decrease in GUS activity from the stem apex to the bottom corresponded to decreases in auxin concentrations in these tissues. High auxin concentration and high GH3::GUS activity were present in the pith tissue, which may provide storage for auxin compounds. GH3 reporter was active in ray cells, paratracheal parenchyma cells, maturing vessels and in cells surrounding maturing phloem fibers but not in the cambium and immature phloem, despite high auxin concentrations in the latter tissues. However, the GH3 promoter in these tissues became active when the plants were exposed to abiotic stresses, like bending or salinity, causing changes in wood anatomy. We suggest that adjustment of the internal auxin balance in wood in response to environmental cues involves GH3 auxin conjugate synthases.

Effects of High Intensity Interval Training on Plasma Levels of GH and IGF-I

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Seyyed Mahmoud Hejazi

2017-04-01

Full Text Available Introduction: It is well-recognized that exercise has a significant impact on the GH/IGF system but less is known about the effects of HIIT on this axis. Aim of the present study was to evaluate the effect of ten weeks of HIIT on plasma levels of GH and IGF-I in healthy men. Methods: Twenty young men (age 23.34 ± 2.56 weight 72.47 ± 12.01 height 174.10 ± 5.75 recruited and randomly assigned into control (n=10 and HIIT (n=12 groups. HIIT protocol was started with 4 cycles. Then, every two weeks one cycle was added to the previous ones. Finally, it was to 8 cycles/ session in tenth weeks that lasted 16 minutes. Blood samples were collected prior to and after HIIT program for all subjects and IGF-I and GH levels were measured. Result: HIIT subjects showed a significant increase in IGF-I (P=0.002, F=12.38. However, no significant change was shown in GH levels (P=0.716, F=0.62. Discussion and conclusion: Our findings indicate that the HIIT caused increase in circulating levels of IGF-I independently from GH levels. Both hormones may contribute to positive effects of anabolic conditions.

The Murid Herpesvirus-4 gL regulates an entry-associated conformation change in gH.

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Laurent Gillet

2008-07-01

Full Text Available The glycoprotein H (gH/gL heterodimer is crucial for herpesvirus membrane fusion. Yet how it functions is not well understood. The Murid Herpesvirus-4 gH, like that of other herpesviruses, adopts its normal virion conformation by associating with gL. However, gH switched back to a gL-independent conformation after virion endocytosis. This switch coincided with a conformation switch in gB and with capsid release. Virions lacking gL constitutively expressed the down-stream form of gH, prematurely switched gB to its down-stream form, and showed premature capsid release with poor infectivity. These data argue that gL plays a key role in regulating a gH and gB functional switch from cell binding to membrane fusion.

Effect of long-term administration of an analog of growth hormone-releasing factor on the GH response in rats.

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Karashima, T; Olsen, D; Schally, A V

1987-06-22

The effect of the repeated or continuous administration of an analog of GH releasing factor (GH-RF), D-Tyr-1, D-Ala-2, Nle-27, GH-RF(1-29)-NH2 (DBO-29), on the subsequent response to this peptide was investigated in pentobarbital-anesthetized male rats. A sc administration of this analog induced a greater and more prolonged GH release than doses 10 times larger of GH-RF(1-29). The GH increase after sc injection of 10 micrograms/kg bw of the analog was greater than that induced by iv administration of 2 micrograms/kg bw of GH-RF(1-44). Pretreatment with 10 micrograms/kg bw of the analog did not affect the pituitary response to a strong stimulus (20 micrograms/kg bw) of GH-RF(1-44), 24 h later. Pretreatment with the analog in doses of 10 micrograms/kg bw, sc twice a day, 5 days per week for 4 weeks, significantly diminished the GH release in response to a sc injection of the analog (10 micrograms/kg bw), as compared to vehicle-pretreated controls (P less than 0.01). On the other hand, a continuous sc administration of 0.4 micrograms/h of the analog to intact rats for 7 days did not result in a decrease in GH response to a sc injection of the analog (10 micrograms/kg bw). Since the rats injected repeatedly with the analog for 4 weeks still showed a marked, although somewhat reduced response, analogs of this type may be useful clinically.

Adjuvant Growth Hormone for Ovulation Induction with Gonadotropins in the Treatment of a Woman with Hypopituitarism

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Ariadne Daniel

2012-01-01

Full Text Available Objective. To report the prestimulation use of adjuvant GH for gonadotropin ovulation induction in a woman with hypopituitarism and GH deficiency who previously failed to respond. Design, Patients, and Measurements. A 31-year-old nulliparous woman presented with hypopituitarism and GH deficiency after failing ovulation induction with high dose gonadotropins. A trial of GH was undertaken for 5 months prior to ovulation induction resulting in normalization of IGF-I levels. Results. Women with hypopituitarism are known to have lower pregnancy rates after ovulation induction with need for higher doses of gonadotropins. A small subset of these patients do not ovulate. This patient had successful ovulation induction and pregnancy with prestimulation GH. Conclusions. This case suggests that the use of adjuvant GH in a GH-deficient patient several months before the use of human menopausal gonadotropin results in ovulation and pregnancy.

The cotton MAPK kinase GhMPK20 negatively regulates resistance to Fusarium oxysporum by mediating the MKK4-MPK20-WRKY40 cascade.

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Wang, Chen; He, Xiaowen; Li, Yuzhen; Wang, Lijun; Guo, Xulei; Guo, Xingqi

2017-11-02

Fusarium wilt is one of the most serious diseases affecting cotton. However, the pathogenesis and mechanism by which Fusarium oxysporum overcomes plant defence responses are unclear. Here, a new group D mitogen-activated protein kinase (MAPK) gene, GhMPK20, was identified and functionally analysed in cotton. GhMPK20 expression was significantly induced by F. oxysporum. Virus-induced gene silencing (VIGS) of GhMPK20 in cotton increased the tolerance to F. oxysporum, whereas ectopic GhMPK20 overexpression in Nicotiana benthamiana reduced F. oxysporum resistance via disruption of the salicylic acid (SA)-mediated defence pathway. More importantly, an F. oxysporum-induced MAPK cascade pathway composed of GhMKK4, GhMPK20 and GhWRKY40 was identified. VIGS of GhMKK4 and GhWRKY40 also enhanced F. oxysporum resistance in cotton, and the function of GhMKK4-GhMPK20 was shown to be essential for F. oxysporum-induced GhWRKY40 expression. Together, our results indicate that the GhMKK4-GhMPK20-GhWRKY40 cascade in cotton plays an important role in the pathogenesis of F. oxysporum. This research broadens our knowledge of the negative role of the MAPK cascade in disease resistance in cotton and provides an important scientific basis for the formulation of Fusarium wilt prevention strategies. © 2017 BSPP AND JOHN WILEY & SONS LTD.

Serum levels of free and total insulin-link growth factor (IGF)-1 and (IGF) binding protein-3 in normal and growth hormone deficient children

International Nuclear Information System (INIS)

Shousha, M.A.; Soliman, S.E.T.; Hafez, H.M.

2008-01-01

Serum levels of total insulin-like growth factor- 1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) reflect endogenous GH secretion in healthy children, which makes them good diagnostic markers for screening GH deficiency (GHD) in short children, although some controversy still exists. Only a minor fraction of the total IGF-1 circulates in its free form, which is believed to be the biologically active form. Serum levels of free IGF-1, total IGF-I and IGFBP-3 were measured in 144 healthy children (72 boys and 72 girls, aged from 0 to 16 years) and in 12 prepubertal GH. deficient (GHD) children to study correlation between the age and free IGF-1, total IGF-1 and IGFBP-3 levels. In healthy subjects (both sexes), serum free IGF-1, total IGF-1 and IGFBP-3 levels were low in infancy, increasing during puberty and declining thereafter. Free IGF-1 in serum occupied about 0.97. 1.45 % of the total IGF-1 values, and the ratios of free IGF-1 to total IGF-1 were significantly increased in the pubertal age groups than in the prepubertal age groups. Serum levels of free IGF-1 showed significant positive correlation with those of total IGF-I and IGFBP-3. Serum free IGF-1, total IGF-1 and IGFBP-3 levels in patients with GHD decreased significantly with increasing degree of hypopituitarism. These observations suggest that the increase in serum free IGF-1 level during puberty was caused by a dramatic increase in total IGF-1 rather than IGFBP-3. Also, high levels of these hormones may play an important role in pubertal growth spurt and may become a useful tool for diagnosing GHD and predicting growth response to long term GH therapy

Jointly Amplified Basal and Pulsatile Growth Hormone (GH) Secretion and Increased Process Irregularity in Women with Anorexia Nervosa

DEFF Research Database (Denmark)

Støving, R K; Veldhuis, J D; Flyvbjerg, A

1999-01-01

Anorexia nervosa (AN) is associated with multiple endocrine alterations. In the majority of AN patients, basal and GHRH-stimulated serum GH levels are increased. The metabolic effects of GH are known to be related to its pulsatile secretory pattern. The present study was performed to examine GH...

Growth hormone therapy: emerging dilemmas.

Science.gov (United States)

Laron, Zvi

2011-06-01

The history of pituitary growth hormone (GH) started 100 years ago but the isolation purification and determination of the chemical structure of the human GH (hGH) took another 50 years. Starting in 1957 hGH was extracted from cadaver pituitaries and its clinical use was restricted to severe GH deficient patient. With the invention of recombinant biosynthetic hGH in 1985; the indications for its use were extended. The major approved medications are GH deficiency and short statured children of various etiologies. This is a critical review of present and future use of human GH. To evaluate the effectiveness of the hGH treatment several pharmaceutical companies established postmarketing follow-up programs which are based on the reliability and cooperation of the treating physicians. Unfortunately they stop when the treatment is terminated and most studies refer to growth stimulation effectiveness during initial years but do not follow the children until final height. The long-term experience enabled to evaluate adverse effects (AE), the majority being due to large dosage. The most serious AE reported are increases in malignancies and early or late mortality in adult age. There is consensus that GH deficient children need replacement therapy. As long-term hGH treatment is expensive and the final height gains in non-GH deficient children small the cost-benefit indications to treat short children without a disease has been questioned. To avoid the need of daily injections, long-acting hGH preparations undergo clinical trials. The future will show their effectiveness and eventual adverse effects.

Evaluation of growth hormone release and human growth hormone treatment in children with cranial irradiation-associated short stature

International Nuclear Information System (INIS)

Romshe, C.A.; Zipf, W.B.; Miser, A.; Miser, J.; Sotos, J.F.; Newton, W.A.

1984-01-01

We studied nine children who had received cranial irradiation for various malignancies and subsequently experienced decreased growth velocity. Their response to standard growth hormone stimulation and release tests were compared with that in seven children with classic GH deficiency and in 24 short normal control subjects. With arginine and L-dopa stimulation, six of nine patients who received radiation had a normal GH response (greater than 7 ng/ml), whereas by design none of the GH deficient and all of the normal children had a positive response. Only two of nine patients had a normal response to insulin hypoglycemia, with no significant differences in the mean maximal response of the radiation and the GH-deficient groups. Pulsatile secretion was not significantly different in the radiation and GH-deficient groups, but was different in the radiation and normal groups. All subjects in the GH-deficient and radiation groups were given human growth hormone for 1 year. Growth velocity increased in all, with no significant difference in the response of the two groups when comparing the z scores for growth velocity of each subject's bone age. We recommend a 6-month trial of hGH in children who have had cranial radiation and are in prolonged remission with a decreased growth velocity, as there is no completely reliable combination of GH stimulation or release tests to determine their response

Quality of porcine blastocysts produced in vitro in the presence of absence of GH

NARCIS (Netherlands)

Kidson, A.; Rubio-Pomar, F.J.; Knegsel, van A.; Tol, van H.T.A.; Hazeleger, W.; Ducro-Steverink, D.W.B.; Colenbrander, B.; Dieleman, S.J.; Bevers, M.M.

2004-01-01

GH receptor (GHR) mRNA is expressed in bovine in vitro produced embryos up to the blastocyst stage and GH improves the quality of bovine embryos by increasing blastocyst cell numbers and reducing the incidence of apoptosis as evaluated by DNA strand-break labelling. Porcine in vitro produced

Muscular dystrophy-related quantitative and chemical changes in adenohypophysis GH-cells in golden retrievers

DEFF Research Database (Denmark)

de Lima, A R; Nyengaard, Jens Randel; Jorge, A A L

2007-01-01

investigated the morphological aspects of the adenohypophysis as well as the total number and size of GH-granulated cells using design-based stereological methods in a limited number of dystrophic and healthy golden retrievers. GH-cells were larger (32.4%) in dystrophic dogs than in healthy animals (p=0...

Health Alert: Adrenal Crisis Causes Death in Some People Who Were Treated with hGH

Science.gov (United States)

... Were Treated with hGH Health Alert: Adrenal Crisis Causes Death in Some People Who Were Treated with hGH ... Adrenal crisis is a serious condition that can cause death in people who lack the pituitary hormone ACTH. ...

Regulation of skeletal growth and mineral acquisition by the GH/IGF-1 axis: Lessons from mouse models.

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Yakar, Shoshana; Isaksson, Olle

2016-06-01

The growth hormone (GH) and its downstream mediator, the insulin-like growth factor-1 (IGF-1), construct a pleotropic axis affecting growth, metabolism, and organ function. Serum levels of GH/IGF-1 rise during pubertal growth and associate with peak bone acquisition, while during aging their levels decline and associate with bone loss. The GH/IGF-1 axis was extensively studied in numerous biological systems including rodent models and cell cultures. Both hormones act in an endocrine and autocrine/paracrine fashion and understanding their distinct and overlapping contributions to skeletal acquisition is still a matter of debate. GH and IGF-1 exert their effects on osteogenic cells via binding to their cognate receptor, leading to activation of an array of genes that mediate cellular differentiation and function. Both hormones interact with other skeletal regulators, such as sex-steroids, thyroid hormone, and parathyroid hormone, to facilitate skeletal growth and metabolism. In this review we summarized several rodent models of the GH/IGF-1 axis and described key experiments that shed new light on the regulation of skeletal growth by the GH/IGF-1 axis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Deficiency of Thrombospondin-4 in Mice Does Not Affect Skeletal Growth or Bone Mass Acquisition, but Causes a Transient Reduction of Articular Cartilage Thickness.

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Anke Jeschke

Full Text Available Although articular cartilage degeneration represents a major public health problem, the underlying molecular mechanisms are still poorly characterized. We have previously utilized genome-wide expression analysis to identify specific markers of porcine articular cartilage, one of them being Thrombospondin-4 (Thbs4. In the present study we analyzed Thbs4 expression in mice, thereby confirming its predominant expression in articular cartilage, but also identifying expression in other tissues, including bone. To study the role of Thbs4 in skeletal development and integrity we took advantage of a Thbs4-deficient mouse model that was analyzed by undecalcified bone histology. We found that Thbs4-deficient mice do not display phenotypic differences towards wildtype littermates in terms of skeletal growth or bone mass acquisition. Since Thbs4 has previously been found over-expressed in bones of Phex-deficient Hyp mice, we additionally generated Thbs4-deficient Hyp mice, but failed to detect phenotypic differences towards Hyp littermates. With respect to articular cartilage we found that Thbs4-deficient mice display transient thinning of articular cartilage, suggesting a protective role of Thbs4 for joint integrity. Gene expression analysis using porcine primary cells revealed that Thbs4 is not expressed by synovial fibroblasts and that it represents the only member of the Thbs gene family with specific expression in articular, but not in growth plate chondrocytes. In an attempt to identify specific molecular effects of Thbs4 we treated porcine articular chondrocytes with human THBS4 in the absence or presence of conditioned medium from porcine synovial fibroblasts. Here we did not observe a significant influence of THBS4 on proliferation, metabolic activity, apoptosis or gene expression, suggesting that it does not act as a signaling molecule. Taken together, our data demonstrate that Thbs4 is highly expressed in articular chondrocytes, where its

GH/IGF-I Transgene Expression on Muscle Homeostasis

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Schwartz, Robert J.

1999-01-01

We propose to test the hypothesis that the growth hormone/ insulin like growth factor-I axis through autocrine/paracrine mechanisms may provide long term muscle homeostasis under conditions of prolonged weightlessness. As a key alternative to hormone replacement therapy, ectopic production of hGH, growth hormone releasing hormone (GHRH), and IGF-I will be studied for its potential on muscle mass impact in transgenic mice under simulated microgravity. Expression of either hGH or IGF-I would provide a chronic source of a growth-promoting protein whose biosynthesis or secretion is shut down in space. Muscle expression of the IGF-I transgene has demonstrated about a 20% increase in hind limb muscle mass over control nontransgenic litter mates. These recent experiments, also establish the utility of hind-limb suspension in mice as a workable model to study atrophy in weight bearing muscles. Thus, transgenic mice will be used in hind-limb suspension models to determine the role of GH/IGF-I on maintenance of muscle mass and whether concentric exercises might act in synergy with hormone treatment. As a means to engineer and ensure long-term protein production that would be workable in humans, gene therapy technology will be used by to monitor muscle mass preservation during hind-limb suspension, after direct intramuscular injection of a genetically engineered muscle-specific vector expressing GHRH. Effects of this gene-based therapy will be assessed in both fast twitch (medial gastrocnemius) and slow twitch muscle (soleus). End-points include muscle size, ultrastructure, fiber type, and contractile function, in normal animals, hind limb suspension, and reambutation.

RNA interference of GhPEPC2 enhanced seed oil accumulation and salt tolerance in Upland cotton.

Science.gov (United States)

Zhao, Yanpeng; Huang, Yi; Wang, Yumei; Cui, Yupeng; Liu, Zhengjie; Hua, Jinping

2018-06-01

Phosphoenolpyruvate carboxylase (PEPCase) mainly produces oxaloacetic acid for tricarboxylic acid (TCA) cycle. Here we reported that GhPEPC2 silencing with PEPC2-RNAi vector could regulate oil and protein accumulation in cottonseeds. In GhPEPC2 transgenic plants, PEPCase activities in immature embryos were significantly reduced, and the oil content in seed kernel was increased 7.3 percentages, whereas total proteins decreased 5.65 percentages. Compared to wild type, agronomical traits of transgenic plant were obviously unaffected. Furthermore, gene expression profile of GhPEPC2 transgenic seeds were investigated using RNA-seq, most lipid synthesis related genes were up-regulated, but amino acid metabolic related genes were down-regulated. In addition, the GhPEPC2 transgenic cotton seedlings were stressed using sodium salts at seedling stage, and the salt tolerance was significantly enhanced. Our observations of GhPEPC2 in cotton would shade light on understanding the regulation of oil content, protein accumulation and salt tolerance enhancement in other plants. Copyright © 2018 Elsevier B.V. All rights reserved.

PCR-RFLP analyses for studying the diversity of GH and Pit-1 genes in Slovak Simmental cattle

Directory of Open Access Journals (Sweden)

Anna Trakovická

2013-10-01

Full Text Available The aim of this study was evaluation of growth hormone (GH and specific pituitary transcription factor (Pit-1 genes diversity in population of 353 Slovak Simmental cows. The analyses were based on single nucleotide polymorphisms GH/AluI and Pit-1/HinfI detections. A polymorphic site of GH gene (AluI has been linked to differences in circulating metabolites, metabolic hormones and milk yield. Bovine Pit-1 is responsible for pituitary development and hormone secreting gene expression, including GH gene. The Pit-1/HinfI locus was associated with growth, milk production and reproduction performance in cattle. Samples of genomic DNA were analyzed by PCR-RFLP method. Digestion of GH gene PCR products with restriction enzyme AluI revealed allele L and V with frequency 0.695 and 0.305, respectively. The digested Pit-1 gene PCR products with enzyme HinfI revealed alleles A (0.249 and B (0.751. Dominant genotypes were for GH gene heterozygous LV (0.47 and for Pit-1 gene homozygous BB (0.56 animals. The observed heterozygosity, effective allele numbers and polymorphism information content of GH/AluI and Pit-1/HinfI bovine loci population were 0.42/0.37, 1.73/1.59 and 0.33/0.30, respectively. The median polymorphic information content of loci was also transferred to the higher observed homozygosity in population (0.58/0.63. Keywords: cattle, growth hormone, leptin, PCR, Pit-1, polymorphism.

Transcriptional regulation of the gltA and tlc genes in Rickettsia prowazekii growing in a respiration-deficient host cell

International Nuclear Information System (INIS)

Cai, J.; Winkler, H.H.

1997-01-01

The regulation of the citrate synthase (gltA) and ATP/ADP translocase (tlc) genes of the obligate intracellular bacterium, Rickettsia prowazekii, was analyzed in rickettsia-infected respiration-deficient G14 cells. The level of the gltA mRNAII and the tlc mRNA was much lower in the total RNA isolated from the infected G 14 cells grown in 1 g/1 glucose (low glucose, GL) medium than in that from infected G 14 cells grown in 4.5 g/l glucose (high glucose, GH) medium. However, the level of the gltA mRNAI relative to 16 S rRNA was the same in GL and GH media. An increase in the level of the gltA mRNAII and the tlc mRNA could be observed as early as 2 hrs after shifting from GL to GH medium. We conclude that, under these experimental conditions, the tlc promoter and the gltA promoter P2, but not gltA promoter P1, were transcriptionally regulated. Key words: Rickettsia prowazekii; gltA gene; tlC gene; transcriptional regulation; G 14 cells (authors)

Beneficial effects of GH/IGF-1 on skeletal muscle atrophy and function in experimental heart failure.

Science.gov (United States)

Dalla Libera, Luciano; Ravara, Barbara; Volterrani, Maurizio; Gobbo, Valerio; Della Barbera, Mila; Angelini, Annalisa; Danieli Betto, Daniela; Germinario, Elena; Vescovo, Giorgio

2004-01-01

Muscle atrophy is a determinant of exercise capacity in heart failure (CHF). Myocyte apoptosis, triggered by tumor necrosis factor-alpha (TNF-alpha) or its second messenger sphingosine (SPH), is one of the causes of atrophy. Growth hormone (GH) improves hemodynamic and cardiac trophism in several experimental models of CHF, but its effect on skeletal muscle in CHF is not yet clear. We tested the hypothesis that GH can prevent skeletal muscle apoptosis in rats with CHF. CHF was induced by injecting monocrotaline. After 2 wk, 2 groups of rats were treated with GH (0.2 mg.kg(-1).day(-1) and 1.0 mg.kg(-1).day(-1)) subcutaneously. A third group of controls had saline. After 2 additional weeks, rats were killed. Tibialis anterior cross-sectional area, myosin heavy chain (MHC) composition, and a study on myocyte apoptosis and serum levels of TNF-alpha and SPH were carried out. The number of apoptotic nuclei, muscle atrophy, and serum levels of TNF-alpha and SPH were decreased with GH at high but not at low doses compared with CHF rats. Bcl-2 was increased, whereas activated caspases and bax were decreased. The MHC pattern in GH-treated animals was similar to that of controls. Monocrotaline slowed down both contraction and relaxation but did not affect specific tetanic force, whereas absolute force was decreased. GH treatment restored contraction and relaxation to control values and brought muscle mass and absolute twitch and tetanic tension to normal levels. These findings may provide an insight into the therapeutic strategy of GH given to patients with CHF to improve exercise capacity.

Hypothalamo-pituitary function after therapy for cancer

International Nuclear Information System (INIS)

Brauner, R.

1995-01-01

Cranial irradiation may result in altered hypothalamo-pituitary function in patients treated for cancer distant from this area. Growth hormone (GH) deficiency is the most frequent complication. The frequency, delay of occurrence and severity of GH deficiency depend on the irradiation dose delivered to this area. The other factors influencing the frequency are the age at irradiations and the fractionation schedule. The frequency of other hypothalamo-pituitary changes is also dose-dependent: thyrotropin and gonadotropin deficiencies occur in 50-60% of cases after 50 Gray, and corticotrophin deficiency in 30%. Low dose cranial irradiations may also induce precocious puberty (onset < 8 yr in girls and < 10 yr in boys). The radiation-induced lesions seem to occur in the hypothalamus rather than in the pituitary. There is generally a good correlation between the GH peak and the growth velocity, but there may be normal growth in spite of GH deficiency after low dose or due to precocious puberty, decreased growth velocity in spite of normal GH peak, due to bone irradiation. Results on final height have been optimized by a better indication of GH therapy and by its association with treatment of precocious puberty. (author). 19 refs

Hypothalamo-pituitary function after therapy for cancer; Retentissement hypothalamo-hypophysaire des traitements des cancers

Energy Technology Data Exchange (ETDEWEB)

Brauner, R. [Paris-5 Univ., 75 (France)]|[Hopital Necker-Enfants-Malades, 75 - Paris (France)

1995-12-31

Cranial irradiation may result in altered hypothalamo-pituitary function in patients treated for cancer distant from this area. Growth hormone (GH) deficiency is the most frequent complication. The frequency, delay of occurrence and severity of GH deficiency depend on the irradiation dose delivered to this area. The other factors influencing the frequency are the age at irradiations and the fractionation schedule. The frequency of other hypothalamo-pituitary changes is also dose-dependent: thyrotropin and gonadotropin deficiencies occur in 50-60% of cases after 50 Gray, and corticotrophin deficiency in 30%. Low dose cranial irradiations may also induce precocious puberty (onset < 8 yr in girls and < 10 yr in boys). The radiation-induced lesions seem to occur in the hypothalamus rather than in the pituitary. There is generally a good correlation between the GH peak and the growth velocity, but there may be normal growth in spite of GH deficiency after low dose or due to precocious puberty, decreased growth velocity in spite of normal GH peak, due to bone irradiation. Results on final height have been optimized by a better indication of GH therapy and by its association with treatment of precocious puberty. (author). 19 refs.

Regulation of His-dTrp-Ala-Trp-dPhe-Lys-NH2 (GHRP-6)-induced GH secretion in the rat.

Science.gov (United States)

Mallo, F; Alvarez, C V; Benitez, L; Burguera, B; Coya, R; Casanueva, F F; Dieguez, C

1993-01-01

His-dTrp-Ala-Trp-dPhe,Lys-NH2(GHRP-6) is a synthetic compound that releases GH in a dose-response and specific manner in several species and that may well be related to an endogenous compound of similar structure. The aim of this study was to investigate the in vivo GH responses to GHRP-6 in pentobarbital anesthetized rats. Specifically and in order to avoid the influence of endogenous GHRH and somatostatin secretion we studied the GH responses to GHRP-6 in animals with surgical ablation of the hypothalamus, confirmed by histological assessment, as well as in hypophysectomyzed-transplanted rats bearing two hypophyses under the renal capsule. Since it has been previously reported that rats pretreated with GHRH (10 micrograms/kg i.p. every 12 h for 15 days) rather than saline-treated rats have greater GH responses to acutely administered GHRH, we compared the self-potentiating effect of chronic GH pretreatment with GHRP-6 (10 micrograms/kg i.p. every 12 h). Furthermore we also studied the influence of estrogens, glucocorticoids, free fatty acids (FFA) and bombesin on somatotroph responsiveness to GHRP-6 in intact rats. We found a greater GH response to GHRP-6 in rats that underwent a surgical ablation of the hypothalamus 36 h prior to the test than in sham-operated rats. A direct stimulatory effect of GHRP-6 on in vivo GH secretion was demonstrated by a clear GH response to GHRP-6 in hypophysectomyzed-transplanted rats. In addition, we found a similar response whether the animals were pretreated with GHRH or GHRP-6 over the previous 2 weeks. Finally, we found that both estrogen- and testosterone-treated rats have greater GH responses to GHRP-6 than untreated rats. On the other hand, chronic dexamethasone administration, acute elevation of circulating FFA levels and bombesin administration markedly inhibited GH responses to GHRP-6. In contrast to the effects exerted on GH responses to GHRP-6 estrogen administration led to a decrease in GH responses to GHRH while

GH response to intravenous clonidine challenge correlates with history of childhood trauma in personality disorder.

Science.gov (United States)

Lee, Royce J; Fanning, Jennifer R; Coccaro, Emil F

2016-05-01

Childhood trauma is a risk factor for personality disorder. We have previously shown that childhood trauma is associated with increased central corticotrophin-releasing hormone concentration in adults with personality disorder. In the brain, the release of corticotrophin-releasing hormone can be stimulated by noradrenergic neuronal activity, raising the possibility that childhood trauma may affect the hypothalamic-pituitary adrenal (HPA) axis by altering brain noradrenergic function. In this study, we sought to test the hypothesis that childhood trauma is associated with blunted growth hormone response to the α-2 adrenergic autoreceptor agonist clonidine. All subjects provided written informed consent. Twenty personality disordered and twenty healthy controls (without personality disorder or Axis I psychopathology) underwent challenge with clonidine, while plasma Growth Hormone (GH) concentration was monitored by intravenous catheter. On a different study session, subjects completed the Childhood Trauma Questionnaire and underwent diagnostic interviews. Contrary to our a priori hypothesis, childhood trauma was associated with enhanced GH response to clonidine. This positive relationship was present in the group of 40 subjects and in the subgroup 20 personality disordered subjects, but was not detected in the healthy control subjects when analyzed separately. The presence of personality disorder was unrelated to the magnitude of GH response. Childhood trauma is positively correlated with GH response to clonidine challenge in adults with personality disorder. Enhanced rather that blunted GH response differentiates childhood trauma from previously identified negative predictors of GH response, such as anxiety or mood disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of the increase in GH and IGF-1 and effectiveness in the treatment on Zacatecas population

International Nuclear Information System (INIS)

Gallegos F, P. I.; Badillo A, V.

2013-10-01

The acromegaly and gigantism are dysfunctions that are caused by hyper-secretion of growth hormone (GH) and of production in liver of growth factor similar to the insulin type 1 (IGF-1) mediated by the GH secretion. The secretor pituitary adenomas of GH are the main cause of the hyper-secretion. The acromegaly and gigantism are manifested respectively by acral alterations and extremities increase, and an excessive growth of the bones. Although a world prevalence of 40-60 cases by inhabitants million is registered, very few formal studies exist that confirm this number. According to the program Epiacro in Mexico is considered a prevalence of 13 cases by inhabitants million. In the Zacatecas State official statistical numbers are not had for these pathologies. Due to the few registrations that exist, or to the cases reported in Mexico, is necessary to evaluate patients with suspicion and with hyper-secretion diagnostic of GH, to contribute and/or to reinforce the health state and national statistics. In this work the GH and IGF-1 concentrations were measured on Zacatecas population to estimate the age range and sex with more probability of suffering this illness, and to evaluate the patients that have received some treatment to check their effectiveness verifying the GH and IGF-1 decrease and being able to obtain normal values. We register 26 patient cases with suspicion of GH hyper-secretion, of these 9 were affected by the illness. The hyper-secretion cases were presented with more frequency in half age adults, being affected in a same way as much men as women. To the end of the study only an affected patient concludes with the pharmacological treatment for the GH hyper-secretion control of a group of 5. (Author)

Resolution of non-alcoholic steatohepatitis after growth hormone replacement in a pediatric liver transplant patient with panhypopituitarism.

Science.gov (United States)

Gilliland, Thomas; Dufour, Sylvie; Shulman, Gerald I; Petersen, Kitt Falk; Emre, Sukru H

2016-12-01

NAFLD is a common condition linked to obesity, type 2 diabetes, and metabolic syndrome. Simple hepatic steatosis is a risk factor for inflammatory reactions in the liver (NASH), which may lead to cirrhosis. While the mechanism is unclear, NAFLD and NASH are associated with panhypopituitarism, which in the pediatric population often results from craniopharyngioma or pituitary adenoma and the sequelae of treatment, causing hypothyroidism, adrenal insufficiency, hypogonadotropic hypogonadism, and GH deficiency. Refractory NAFLD in panhypopituitarism may be amenable to GH replacement. Here, we report a pediatric case of NASH secondary to panhypopituitarism from craniopharyngioma, which recurred by 11 months after LDLT. Despite low-dose GH replacement, the patient remained GH deficient. Pubertal dosed GH therapy led to rapid and complete resolution of hepatic steatosis, which we tracked using serial 1 H MRS. Pediatric patients with NASH cirrhosis secondary to panhypopituitarism can be good candidates for liver transplantation, but hormone deficiencies predispose to recurrence after transplant. High-dose GH replacement should be considered in pediatric patients with GH deficiency and recurrent disease. A multidisciplinary team approach is essential for successful outcomes. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Molecular engineering of fungal GH5 and GH26 beta-(1,4-mannanases toward improvement of enzyme activity.

Directory of Open Access Journals (Sweden)

Marie Couturier

Full Text Available Microbial mannanases are biotechnologically important enzymes since they target the hydrolysis of hemicellulosic polysaccharides of softwood biomass into simple molecules like manno-oligosaccharides and mannose. In this study, we have implemented a strategy of molecular engineering in the yeast Yarrowia lipolytica to improve the specific activity of two fungal endo-mannanases, PaMan5A and PaMan26A, which belong to the glycoside hydrolase (GH families GH5 and GH26, respectively. Following random mutagenesis and two steps of high-throughput enzymatic screening, we identified several PaMan5A and PaMan26A mutants that displayed improved kinetic constants for the hydrolysis of galactomannan. Examination of the three-dimensional structures of PaMan5A and PaMan26A revealed which of the mutated residues are potentially important for enzyme function. Among them, the PaMan5A-G311S single mutant, which displayed an impressive 8.2-fold increase in kcat /KM due to a significant decrease of KM, is located within the core of the enzyme. The PaMan5A-K139R/Y223H double mutant revealed modification of hydrolysis products probably in relation to an amino-acid substitution located nearby one of the positive subsites. The PaMan26A-P140L/D416G double mutant yielded a 30% increase in kcat /KM compared to the parental enzyme. It displayed a mutation in the linker region (P140L that may confer more flexibility to the linker and another mutation (D416G located at the entrance of the catalytic cleft that may promote the entrance of the substrate into the active site. Taken together, these results show that the directed evolution strategy implemented in this study was very pertinent since a straightforward round of random mutagenesis yielded significantly improved variants, in terms of catalytic efiiciency (kcat/KM.

Evaluation of the Role of the opgGH Operon in Yersinia pseudotuberculosis and Its Deletion during the Emergence of Yersinia pestis

Science.gov (United States)

Quintard, Kévin; Dewitte, Amélie; Reboul, Angéline; Madec, Edwige; Bontemps-Gallo, Sébastien; Dondeyne, Jacqueline; Marceau, Michaël; Simonet, Michel

2015-01-01

The opgGH operon encodes glucosyltransferases that synthesize osmoregulated periplasmic glucans (OPGs) from UDP-glucose, using acyl carrier protein (ACP) as a cofactor. OPGs are required for motility, biofilm formation, and virulence in various bacteria. OpgH also sequesters FtsZ in order to regulate cell size according to nutrient availability. Yersinia pestis (the agent of flea-borne plague) lost the opgGH operon during its emergence from the enteropathogen Yersinia pseudotuberculosis. When expressed in OPG-negative strains of Escherichia coli and Dickeya dadantii, opgGH from Y. pseudotuberculosis restored OPGs synthesis, motility, and virulence. However, Y. pseudotuberculosis did not produce OPGs (i) under various growth conditions or (ii) when overexpressing its opgGH operon, its galUF operon (governing UDP-glucose), or the opgGH operon or Acp from E. coli. A ΔopgGH Y. pseudotuberculosis strain showed normal motility, biofilm formation, resistance to polymyxin and macrophages, and virulence but was smaller. Consistently, Y. pestis was smaller than Y. pseudotuberculosis when cultured at ≥37°C, except when the plague bacillus expressed opgGH. Y. pestis expressing opgGH grew normally in serum and within macrophages and was fully virulent in mice, suggesting that small cell size was not advantageous in the mammalian host. Lastly, Y. pestis expressing opgGH was able to infect Xenopsylla cheopis fleas normally. Our results suggest an evolutionary scenario whereby an ancestral Yersinia strain lost a factor required for OPG biosynthesis but kept opgGH (to regulate cell size). The opgGH operon was presumably then lost because OpgH-dependent cell size control became unnecessary. PMID:26150539

Evaluation of the Role of the opgGH Operon in Yersinia pseudotuberculosis and Its Deletion during the Emergence of Yersinia pestis.

Science.gov (United States)

Quintard, Kévin; Dewitte, Amélie; Reboul, Angéline; Madec, Edwige; Bontemps-Gallo, Sébastien; Dondeyne, Jacqueline; Marceau, Michaël; Simonet, Michel; Lacroix, Jean-Marie; Sebbane, Florent

2015-09-01

The opgGH operon encodes glucosyltransferases that synthesize osmoregulated periplasmic glucans (OPGs) from UDP-glucose, using acyl carrier protein (ACP) as a cofactor. OPGs are required for motility, biofilm formation, and virulence in various bacteria. OpgH also sequesters FtsZ in order to regulate cell size according to nutrient availability. Yersinia pestis (the agent of flea-borne plague) lost the opgGH operon during its emergence from the enteropathogen Yersinia pseudotuberculosis. When expressed in OPG-negative strains of Escherichia coli and Dickeya dadantii, opgGH from Y. pseudotuberculosis restored OPGs synthesis, motility, and virulence. However, Y. pseudotuberculosis did not produce OPGs (i) under various growth conditions or (ii) when overexpressing its opgGH operon, its galUF operon (governing UDP-glucose), or the opgGH operon or Acp from E. coli. A ΔopgGH Y. pseudotuberculosis strain showed normal motility, biofilm formation, resistance to polymyxin and macrophages, and virulence but was smaller. Consistently, Y. pestis was smaller than Y. pseudotuberculosis when cultured at ≥ 37°C, except when the plague bacillus expressed opgGH. Y. pestis expressing opgGH grew normally in serum and within macrophages and was fully virulent in mice, suggesting that small cell size was not advantageous in the mammalian host. Lastly, Y. pestis expressing opgGH was able to infect Xenopsylla cheopis fleas normally. Our results suggest an evolutionary scenario whereby an ancestral Yersinia strain lost a factor required for OPG biosynthesis but kept opgGH (to regulate cell size). The opgGH operon was presumably then lost because OpgH-dependent cell size control became unnecessary. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Small interfering RNAs from bidirectional transcripts of GhMML3_A12 regulate cotton fiber development.

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Wan, Qun; Guan, Xueying; Yang, Nannan; Wu, Huaitong; Pan, Mengqiao; Liu, Bingliang; Fang, Lei; Yang, Shouping; Hu, Yan; Ye, Wenxue; Zhang, Hua; Ma, Peiyong; Chen, Jiedan; Wang, Qiong; Mei, Gaofu; Cai, Caiping; Yang, Donglei; Wang, Jiawei; Guo, Wangzhen; Zhang, Wenhua; Chen, Xiaoya; Zhang, Tianzhen

2016-06-01

Natural antisense transcripts (NATs) are commonly observed in eukaryotic genomes, but only a limited number of such genes have been identified as being involved in gene regulation in plants. In this research, we investigated the function of small RNA derived from a NAT in fiber cell development. Using a map-based cloning strategy for the first time in tetraploid cotton, we cloned a naked seed mutant gene (N1 ) encoding a MYBMIXTA-like transcription factor 3 (MML3)/GhMYB25-like in chromosome A12, GhMML3_A12, that is associated with fuzz fiber development. The extremely low expression of GhMML3_A12 in N1 is associated with NAT production, driven by its 3' antisense promoter, as indicated by the promoter-driven histochemical staining assay. In addition, small RNA deep sequencing analysis suggested that the bidirectional transcriptions of GhMML3_A12 form double-stranded RNAs and generate 21-22 nt small RNAs. Therefore, in a fiber-specific manner, small RNA derived from the GhMML3_A12 locus can mediate GhMML3_A12 mRNA self-cleavage and result in the production of naked seeds followed by lint fiber inhibition in N1 plants. The present research reports the first observation of gene-mediated NATs and siRNA directly controlling fiber development in cotton. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Inflammation and linear bone growth: the inhibitory role of SOCS2 on GH/IGF-1 signaling.

Science.gov (United States)

Farquharson, Colin; Ahmed, S Faisal

2013-04-01

Linear bone growth is widely recognized to be adversely affected in children with chronic kidney disease (CKD) and other chronic inflammatory disorders. The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) pathway is anabolic to the skeleton and inflammatory cytokines compromise bone growth through a number of different mechanisms, which include interference with the systemic as well as the tissue-level GH/IGF-1 axis. Despite attempts to promote growth and control disease, there are an increasing number of reports of the persistence of poor growth in a substantial proportion of patients receiving rhGH and/or drugs that block cytokine action. Thus, there is an urgent need to consider better and alternative forms of therapy that are directed specifically at the mechanism of the insult which leads to abnormal bone health. Suppressor of cytokine signaling 2 (SOCS2) expression is increased in inflammatory conditions including CKD, and is a recognized inhibitor of GH signaling. Therefore, in this review, we will focus on the premise that SOCS2 signaling represents a critical pathway in growth plate chondrocytes through which pro-inflammatory cytokines alter both GH/IGF-1 signaling and cellular function.

GH/IGF-I axis and matrix adaptation of the musculotendinous tissue to exercise in humans

DEFF Research Database (Denmark)

Heinemeier, K M; Mackey, Abigail; Doessing, S

2012-01-01

cells (satellite cells), as increased satellite cell numbers are found in human muscle with increased GH/IGF-I levels, despite no change in myofibrillar protein synthesis. Although advanced age is associated with both a reduction in the GH/IGF-I axis activity, and in skeletal muscle mass (sarcopenia...

Role of the new growth hormone-releasing secretagogues in the diagnosis of some hypothalamopituitary pathologies.

Science.gov (United States)

Casanueva, F F; Micic, D; Pombo, M; Leal, A; Bokser, L; Zugaza, J L; Dieguez, C

1996-08-01

Growth hormone (GH)-releasing hormone (GHRH) and somatostatin have a dominant role in regulating GH secretion. However, results of studies using the new class of GH secretogogues, particularly GHRP-6, indicate that there may also be other, as yet undefined, hypothalamic mechanisms involved. Studies in adults with hypothalamopituitary disconnection (functional pituitary stalk transection), show GHRP-6-mediated GH release to be completely blocked, indicating a main action at the hypothalamic rather than the pituitary level. The synergistic effect of GHRH plus GHRP-6 administration on GH release seen in normal adults (and virtually unaffected by age, obesity, or sex) is also absent in these patients, providing further support for this conclusion. Studies of the effects of GHRP-6 in children with GH deficiency due to perinatal pituitary stalk transection have produced similar findings. It is suggested that the combined GHRH plus GHRH-6 test should be a promising tool for diagnosing GH deficiency states in both children and adults, and may identify a subgroup of patients with GH deficiency caused by interruption of the hypothalamopituitary connection.

Effects of growth hormone (GH) treatment on body fluid distribution in patients undergoing elective abdominal surgery

DEFF Research Database (Denmark)

Møller, Jacob; Jensen, Martin Bach; Frandsen, E.

1998-01-01

OBJECTIVE: To investigate the possible beneficial effects of growth hormone (GH) in catabolic patients we examined the impact of GH on body fluid distribution in patients with ulcerative colitis undergoing elective abdominal surgery. DESIGN AND MEASUREMENTS: Twenty-four patients (14 female, 10 male...... at day -2 and at day 7, and body composition was estimated by dual X-ray absorptiometry and bioimpedance. Changes in body weight and fluid balance were recorded and hence intracellular volume was assessed. RESULTS: During placebo treatment body weight decreased 4.3 +/- 0.6 kg; during GH treatment body.......05). Plasma renin and aldosterone remained unchanged in both study groups. CONCLUSION: Body weight, plasma volume and intracellular volume is preserved during GH treatment in catabolic patients and ECV is increased. From a therapeutic point of view these effects may be desirable under conditions of surgical...

Adipokine zinc-α2-glycoprotein regulated by growth hormone and linked to insulin sensitivity.

Science.gov (United States)

Balaz, Miroslav; Ukropcova, Barbara; Kurdiova, Timea; Gajdosechova, Lucia; Vlcek, Miroslav; Janakova, Zuzana; Fedeles, Jozef; Pura, Mikulas; Gasperikova, Daniela; Smith, Steven R; Tkacova, Ruzena; Klimes, Iwar; Payer, Juraj; Wolfrum, Christian; Ukropec, Jozef

2015-02-01

Hypertrophic obesity is associated with impaired insulin sensitivity and lipid-mobilizing activity of zinc-α2-glycoprotein. Adipose tissue (AT) of growth hormone (GH) -deficient patients is characterized by extreme adipocyte hypertrophy due to defects in AT lipid metabolism. It was hypothesized that zinc-α2-glycoprotein is regulated by GH and mediates some of its beneficial effects in AT. AT from patients with GH deficiency and individuals with obesity-related GH deficit was obtained before and after 5-year and 24-month GH supplementation therapy. GH action was tested in primary human adipocytes. Relationships of GH and zinc-α2-glycoprotein with adipocyte size and insulin sensitivity were evaluated in nondiabetic patients with noncancerous cachexia and hypertrophic obesity. AT in GH-deficient adults displayed a substantial reduction of zinc-α2-glycoprotein. GH therapy normalized AT zinc-α2-glycoprotein. Obesity-related relative GH deficit was associated with almost 80% reduction of zinc-α2-glycoprotein mRNA in AT. GH increased zinc-α2-glycoprotein mRNA in both AT of obese men and primary human adipocytes. Interdependence of GH and zinc-α2-glycoprotein in regulating AT morphology and metabolic phenotype was evident from their relationship with adipocyte size and AT-specific and whole-body insulin sensitivity. The results demonstrate that GH is involved in regulation of AT zinc-α2-glycoprotein; however, the molecular mechanism linking GH and zinc-α2-glycoprotein in AT is yet unknown. © 2014 The Obesity Society.

Adenomas produtores de GH: Análise de 20 casos

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Tella Jr Oswaldo Inácio de

2002-01-01

Full Text Available Os adenomas produtores de GH podem ser mono, bi ou pluri-hormonais. A associação mais frequente do GH é com a sub unidade alfa ou com a prolactina. Apresentam-se com as alterações clássicas de acromegalia, mas quando produzem mais que um hormônio podem apresentar sintomas visuais. Os mono-hormonais são geralmente microadenomas e os outros dois grupos tendem a ser macroadenomas. Analisamos nossa experiência com 20 casos deste tipo de adenomas e mostramos o resultado cirúrgico, que foi bastante satisfatório para o grupo mono-hormonal. A radioterapia deve ser considerada quando a ressecção não foi total.

Suppression of prolactin gene expression in GH cells correlates with site-specific DNA methylation.