Growth Hormone & Igf Research最新文献

The purpose of this study was to examine the responses of growth hormone (GH) and insulin-like growth factor-I (IGFI) to intense heavy resistance exercise in highly trained men and women to determine what sex-dependent responses may exist. Subjects were highly resistance trained men (N = 8, Mean ± SD; age, yrs., 21 ± 1, height, cm, 175.3 ± 6.7, body mass, kg, 87.0 ± 18.5, % body fat, 15.2 ± 5.4, squat X body mass, 2.1 ± 0.4; and women (N = 7; Mean ± SD, age, yrs. 24 ± 5, height, cm 164.6 ± 6.7, body mass, kg 76.4 ± 8.8, % body fat, 26.9 ± 5.3, squat X body mass, 1.7 ± 0.6). An acute resistance exercise test protocol (ARET) consisted of 6 sets of 10 repetitions at 80% of the 1 RM with 2 min rest between sets was used as the stressor. Blood samples were obtained pre-exercise, after 3 sets, and then immediately after exercise (IP), 5, 15, 30, and 70 min post-exercise for determination of blood lactate (HLa), and plasma glucose, insulin, cortisol, and GH. Determination of plasma concentrations of IGFI, IGF binding proteins 1, 2, and 3 along with molecular weight isoform factions were determined at pre, IP and 70 min. GH significantly (P ≤ 0.05) increased at all time points with resting concentrations significantly higher in women. Significant increases were observed for HLa, glucose, insulin, and cortisol with exercise and into recovery with no sex-dependent observations. Women showed IGF-I values that were higher than men at all times points with both seeing exercise increases. IGFBP-1 and 2 showed increase with exercise with no sex-dependent differences. IGFBP-3 concentrations were higher in women at all-time points with no exercise induced changes. Both women and men saw an exercise induced increase with significantly higher values in GH in only the mid-range (30-60 kD) isoform.  Only women saw an exercise induced increase with significantly higher values for IGF fractions only in the mid-range (30–60 kD) isoform, which were significantly greater than the men at the IP and 70 min post-exercise time points. In conclusion, the salient findings of this investigation were that in highly resistance trained men and women, sexual dimorphisms exist but appear different from our prior work in untrained men and women and appear to support a sexual dimorphism related to compensatory aspects in women for anabolic mediating mechanisms in cellular interactions.

Aims/hypothesis

Although IGF-1 is known to promote organ growth, including exocrine pancreas, the association between plasma IGF-1 levels and pancreatic size remains unclear in diabetic patients.

Methods

This cross-sectional study was designed to investigate the correlations among pancreatic volume (PV) based on computed tomography, IGF-1 levels, age- and sex-adjusted IGF-1 levels (IGF-1 Z-score), and C-peptide levels in patients with type 1 diabetes (T1D) (n = 51) and type 2 diabetes (T2D) (n = 104) in a Japanese population.

Results

PV was significantly correlated with body weight (BW) in both types of diabetes. PV adjusted for BW (PV/BW), IGF-1 Z-score and C-peptide levels were significantly lower in patients with T1D than T2D. There was a significant positive correlation between C-peptide levels and PV/BW in both subtypes of diabetes. IGF-1 Z-scores were significantly correlated with PV/BW in patients with T1D (r = 0.37, P = 0.007), but not T2D. Although IGF-1 Z-scores were not correlated with age, age of disease onset, disease duration, HbA1c, or C-peptide levels in both types of diabetes, a multivariable liner regression analysis revealed that IGF-1 Z-score and C-peptide levels were independent correlates of PV/BW in T1D patients, while C-peptide levels were a sole correlate in T2D.

Conclusions/interpretation

Decreased IGF-1 levels might be one causal factor for smaller pancreas in patients with T1D.

Objective

Acromegaly is a rare, pituitary hormonal disorder that requires improved awareness worldwide. The objective of this analysis was to quantify the clinical and economic burden of comorbidities for patients with acromegaly and examine the influence of biochemical control on these outcomes.

Study design

Markov cohort decision analytic model consisting of two states, including alive (with and without comorbidity) and dead.

Methods

A cohort of patients with acromegaly who had achieved biochemical control, a cohort of patients with acromegaly who had not achieved biochemical control, and a cohort of individuals from the general US population were tracked over a lifetime time horizon. The model tracked the proportion of the alive population that had each comorbidity based on age, sex, presence of acromegaly, and biochemical control status. The proportion of patients with each acromegaly-associated comorbidity were assigned comorbidity-associated costs, disutilities, and increased risk of mortality.

Results

Compared with the general population, controlled acromegaly resulted in $192,000 additional comorbidity-related costs, 0.7 fewer years of life, 2.9 fewer quality-adjusted life years, and 1.1 more comorbidities across the remaining lifespan. Compared with the general population, uncontrolled acromegaly resulted in $285,000 additional comorbidity-related costs, 0.9 fewer years of life, 4.2 fewer quality-adjusted life years, and 1.6 more comorbidities across the remaining lifespan.

Conclusions

Achieving biochemical control is associated with improvements in cost, quality of life, and mortality, albeit not to the level of the general population. A multimodal treatment strategy including biochemical control and management of comorbidities is necessary to improve patient outcomes.

Testosterone and estrogen concentrations progressively increase during puberty, and in association with growth hormone (GH), lead to the increase in height velocity known as the pubertal growth spurt. Very limited information is available however, regarding the possible effects of sex steroids over GH cellular sensitivity.

Objective

To investigate the effects of different concentrations of testosterone, estradiol and dihydrotestosterone over the GH intracellular signaling pathway.

Methods

We evaluated the effects of these sex steroids on the nuclear phosphorylation of STAT5b and IGF-1 expression, in HEPG2 human hepatoma cells. In addition, we studied whether Tamoxifen (TAM), can modulate these effects.

Results

The highest concentration of T tested (10 ng/mL) co-incubated with a fixed concentration of GH (40 ng/mL) increased nuclear STAT5b phosphorylation compared with GH alone (1.34 ± 0.2 vs 0.6 ± 0.09 AU; *p < 0.05), as well as IGF-1 expression (0.6 ± 0.03 vs 0.32 ± 0.05 AU; *p < 0.05). This effect was not observed with lower concentrations of T tested (1 and 5 ng/mL). A similar increase in nuclear STAT5b phosphorylation was observed with the lowest concentration of E₂ tested (20 pg/mL), co-incubated with the same fixed concentration of GH (3.6 ± 0.5 vs 1.28 ± 0.33 AU; *p < 0.05). This effect was also associated with an increase in IGF-1 expression (0.73 ± 0.02 vs 0.39 ± 0.04 AU; *p < 0.05). These results were not observed with higher concentrations of E₂ tested (75 and 200 pg/mL). DHT at concentrations of 0.1, 0.25 and 0.5 ng/mL, co-stimulated with GH, did not change cytoplasmic STAT5b phosphorylation, nuclear STAT5b or IGF-1 expression. In addition, the co-incubation of TAM with the highest concentration of T tested (10 ng/mL) and GH (40 ng/mL) did not change cytoplasmic, nuclear pSTAT5 levels or IGF-1 expression.

Conclusions

T and E₂ potentiate the GH signaling pathway in a concentration-dependent fashion. The observation that the non-aromatizable androgen dihydrotestosterone does not stimulate this pathway, and that the effects of T are blocked with TAM, suggests that the effects of T over the GH signaling pathway appear to be mediated by estrogen.

Objective

Acromegaly patients were reported to have an increased arterial stiffness that could contribute to the frequent cardiovascular complications in this population. The chronic excess of GH and IGF-1 may lead to arterial stiffening via different mechanisms, including hypertension, impaired glucose tolerance and dyslipidemia, however, it is not known whether the activation of GH/IGF-1 axis might influence arterial stiffening independently of cardiovascular risk factors. The objective of this prospective case-control study was to compare arterial stiffness assessed with pulse-wave velocity (PWV) in acromegaly versus non-acromegaly group with similar cardiovascular risk profile.

Design

This prospective case-control study included 27 patients with active acromegaly, who underwent the assessment of clinical, physiological, biochemical parameters and the evaluation of PWV with applanation tonometry. We used “The epidemiology of cardiovascular disease in different regions of the Russian Federation” study database (n = 522) to establish a non-acromegaly control group with similar cardiovascular risk profile (n = 54). Non-acromegaly control participants underwent the same assessment as acromegaly patients except for the measurement of serum GH and IGF-1 levels. We compared PWV in acromegaly patients to the general non-acromegaly cohort and its subset, matched with acromegaly patients for cardiovascular risk factors. We also investigated the associations of PWV with clinical, physiological and biochemical parameters in acromegaly and non-acromegaly group using correlation and regression analysis with adjustment for age and sex.

Results

Acromegaly patients had lower PWV (6.70 (5.75–7.65) m/s) compared to unmatched non-acromegaly control cohort (7.50 (6.70–8.57) m/s, p = 0.01) and to the non-acromegaly control group matched for cardiovascular risk factors (7.45 (6.73–8.60), p < 0.01). In non-acromegaly control group PWV was associated with BMI (ρ = 0.40, p < 0.01; β = 0.09, p < 0.01), obesity (r = 0.46, p < 0.01; β = 1.36, p < 0.01), systolic blood pressure (ρ = 0.60, p < 0.01; β = 0.05, p < 0.01), diastolic blood pressure (ρ = 0.62, p < 0.01; β = 0.07, p < 0.01), triglycerides (ρ = 0.55, p < 0.01; β = 0.58, p = 0.04), glucose (ρ = 0.54, p < 0.01; β = 0.70, p < 0.01) and diabetes (r = 0.40, p < 0.01; β = 1.10, p = 0.03), while in acromegaly group PWV was associated with IGF-1 expressed in mcg/ml (ρ = −0.49, p ≤0.01; β = −0.002, p ≤0.01) and in percentage of the upper limit of the normal (ρ = −0.47, p = 0.01; β = −0.005, p ≤0.01) as well as with diu