Effects of growth hormone administration in human obesity

OBJECTIVE: To summarize the reports in the literature regarding the effect of growth hormone (GH) treatment of obesity. RESEARCH METHODS AND PROCEDURES: Clinical trials of GH treatment of obese adults were reviewed and summarized. Specifically, information regarding the effects of GH on body fat and body fat distribution, glucose tolerance/insulin resistance, and adverse consequences of treatment were recorded. RESULTS: GH administered together with hypocaloric diets did not enhance fat loss or preserve lean tissue mass. No studies provided strong evidence for an independent beneficial effect of GH on visceral adiposity. In all but one study, glucose tolerance during GH treatment suffered relative to placebo. CONCLUSION: The bulk of studies indicate little or no beneficial effects of GH treatment of obesity despite the low serum GH concentrations associated with obesity.     

卵泡刺激素受体基因失活突变导致卵巢功能减退的研究进展

卵泡刺激素（follicle-stimulating hormone,FSH）通过激活靶细胞上特定的FSH受体（FSH receptor,FSHR）而发挥作用。FSHR对女性卵泡的发育和雌二醇生成,以及对男性睾丸支持细胞的功能维持和精子形成具有至关重要的作用。在过去的二十余年中,已通过较多的病例鉴定了 FS...     

Antimullerian hormone and obesity: insights in oral contraceptive users

Background

The study was conducted to examine the impact of oral contraceptives (OCs) on serum antimullerian hormone (AMH) levels by obesity status in reproductive-age women.

Study Design

Ovulatory women, ages 18-35 years, of normal (<25 kg/m²; n=10) and obese (>30 kg/m²; n=10) body mass index (BMI) received a low-dose OC (20 mcg ethinyl estradiol/100 mcg levonorgestrel) for two cycles. Serum samples obtained at several time points during active pill use and hormone-free intervals were analyzed for AMH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and inhibin B.

Results

AMH levels did not differ by OC cycle day in either BMI group. On average, AMH levels were 34% lower in the obese group (2.9±2.1 vs. 4.4±1.8 ng/mL, p<.05). Modeling to determine differences in AMH throughout the cycle based on obesity status demonstrated significantly lower levels (p<.05), whereas serum AMH, FSH, LH, estradiol and inhibin B levels revealed no correlations when all time points were included.

Conclusions

In reproductive-age women, serum AMH levels do not appear to fluctuate during OC use, but AMH levels are significantly lower in obese women. Lower levels do not appear to be due to differences in gonadotropin levels or ovarian activity.     

重组人生长激素体外干预人肝癌细胞生长及受体表达

目的研究体外环境下重组人生长激素（rhGH）对生长激素受体（GHR）不同表达状态的人肝癌细胞株增殖、凋亡及其细胞膜表面GHR密度的影响。方法体外培养人肝癌细胞株HepG-2、SMMC7721和QGY-7701,采用免疫细胞化学方法检测这3种肝癌细胞GHR的表达。每种肝癌细胞根据不同处理分为4组：未处理组、50ng／mlrhGH干预组、100ng／mlrhGH干预组、200ng／mlrhGH干预组。采用四甲基偶氮唑蓝比色法、羟基荧光素二醋酸盐琥珀酰亚胺脂（CFSE）荧光染色法、酶联免疫吸附法分析不同浓度rhGH对人肝癌细胞系的细胞生长、增殖、胰岛素样生长因子-1（IGF-1）分泌等的影响。流式、放射性受体分析方法检测rhGH处理后细胞膜表面GHR表达情况。结果细胞株HepG-2高表达GHR;与未处理组相比,50、100、200ng／mlrhGH干预24h后生长率明显增高为：107．705％、114．181％、107．406％（P〈0．05）,48h后生长率明显增高为：109．594％、114．156％、109．292％（P〈0．05）;CFSE荧光强度明显减弱（P〈0．05）;50、100、200ng／mlrhGH干预组24h后下游蛋白IGF-1分别为（236．94±19．07）、（247．16±14．56）、（217．94±33．61）pg／ml,明显高于未处理组的（173．86±27．46）pg/ml（P〈0．05）;50、100、200ng／mlrhGH干预后,流式细胞术检测胞膜表面GHR表达情况,荧光强度较未处理组明显增加（P〈0．05）;放射性受体分析法检测50、100、200ng／mlrhGH干预后胞膜表面GHR位点数（10^3／细胞）分别为：8．44±0．24、9．40±0．51、8．33±0．31,明显多于空白对照组的7．51±0．54（P〈0．05）。细胞株SMMC7721弱表达GHR,细胞株QGY-7701未表达GHR,与未处理组比,rhGH干预组生长率、CFSE荧光强度、下游蛋白IGF-1、GHR表达差异均无统计学意义（P〉0．05）。结论体外环境下,rhGH可以促进GHR高表达人肝癌细胞株HepG-2增殖,提高其IGF-1的表达量和增加其胞膜GHR密度;但不促进人肝癌细胞株QGY-7701、SMMC7721增殖,不能使其GHR表达状态发生改变。     

重组人生长激素体外干预人肝癌细胞生长及受体表达

24、9.40±0.51、8.33±0.31,明显多于空白对照组的7.51±0.54(P＜0.05).细胞株SMMC7721弱表达GHR,细胞株QGY-7701未表达GHR,与未处理组比,rhGH干预组生长率、CFSE荧光强度、下游蛋白IGF-1、GHR表达差异均无统计学意义(P＞0.05).结论 体外环境下,rhGH可以促进GHR高表达人肝癌细胞株HepG-2增殖,提高其IGF-1的表达量和增加其胞膜GHR密度;但不促进人肝癌细胞株QGY-7701、SMMC7721增殖,不能使其GHR表达状态发生改变.     

人Nrf2蛋白的结构与功能分析

目的氧化应激与多种急性或慢性疾病相关,核因子红血球相关因子2(nuclear factor erythroid 2-related factor 2,Nrf2)作为细胞感受氧化还原状态的关键转录调控因子,是细胞抗氧化系统中的关键调控蛋白,深入了解该蛋白的结构与生物学功能,对防治相关疾病具有重要意义.方法利用NCBI、E...     

Biomarkers and functional foods for obesity and diabetes

Obesity has reached epidemic proportions in many countries around the world. Because of the close relationship between obesity and type 2 diabetes, an epidemic of diabetes is close behind the obesity epidemic. Preventing and treating obesity is becoming an increasing priority. In the United States, over 60 % of the adult population is overweight or obese and thus at increased risk of developing diabetes and cardiovascular disease. While the aetiology of obesity and diabetes is complex, diet clearly plays an important role both in the development and management of these diseases. There is interest in functional foods that could help in prevention and/or management of obesity and type 2 diabetes. This could involve food products that help management of 'hunger' or that increase 'satiety'. It could also involve foods that contribute to more inefficient use of ingested energy (i.e. foods that stimulate energy expenditure more than would be expected from their energy content). As the concept of insulin sensitivity becomes generally more accepted by health care professionals and the public, foods may be targeted towards maximizing insulin sensitivity and towards 'prevention' of diabetes. In addition to foods that impact upon body weight, these may include foods that affect the glucose and/or insulin levels that are seen either following the ingestion of food or later in the day. The present paper reviews the complex aetiology of obesity and diabetes and considers a potential role for functional foods in prevention and treatment of obesity and diabetes.     

Growth hormone receptor antagonists: potential indications

Pegvisomant is a mutated human growth hormone molecule, which binds to the growth hormone receptor. This binding, however, does not lead to signal transduction. Therefore, in high concentrations pegvisomant acts as a growth hormone receptor antagonist. In a short term study (3 months) pegvisomant was shown to be an effective treatment for acromegaly. On theoretical grounds decreasing the biological effects of growth hormone in patients with diabetes mellitus could have a favourable impact on the severity of the secondary complications associated with this disease. Animal models for diabetic retino- and nephropathy are in accordance with this concept. Human data are lacking but clinical studies investigating the effect of pegvisomant in diabetes mellitus are in preparation. Growth hormone, either directly or via its downstream effector insulin-like growth factor-I (IGF-I) has been implicated as an important factor in the growth of malignant tumours. Animal studies in which human colon and breast cancer models were used showed that pegvisomant can powerfully decrease tumour growth. Studies in cancer patients have not yet started.     

D2 dopamine receptor gene and obesity

The prevalence of Taql A D₂ dopamine receptor (DRD2) alleles was determined in 73 obese women and men. In this sample with a mean body mass index of 35.1, the A1 (minor) allele of the DRD2 gene was present in 45.2% of these nonalcohol, nondrug abusing subjects. The DRD2 A1 allele was not associated with a number of cardiovascular risk factors examined, including blood lipids (cholesterol, high-density lipoprotein [HDL]- and low-density lipoprotein [LDL]-cholesterol, and triglycerides). However, phenotypic factors characterized by the presence of parental history and postpuberty onset of obesity as well as carbohydrate preference were associated with obese subjects carrying the A1 allele. The cumulative number of these three factors was positively and significantly (p < .0002) related to A1 allelic prevalence. The data showing an association of the minor allele of the DRD2 gene with phenotypic characteristics suggest that this gene, located on q22–q23 region of chromosome 11, confers susceptibility to a subtype of this disorder. © 1994 by John Wiley & Sons, Inc.     

Insulin resistance and obesity: resistin, a hormone secreted by adipose tissue

A newly discovered hormone named adipocyte-secreted factor, or resistin, is secreted by adipocytes in mice. Expression of resistin is low during food deprivation and in diabetes, and increased greatly during refeeding and insulin treatment. It is found in serum in mice and humans, and is greatly increased in obesity. Resistin inhibits adipocyte differentiation and may function as a feedback regulator of adipogenesis. Administration of resistin to mice resulted in increased glucose production and blood glucose levels. Therefore, resistin also functions as a regulator of glucose homeostasis and a physiologic antagonist to hepatic insulin action.     

Growth hormone receptor polymorphism and growth hormone therapy response in children: a Bayesian meta-analysis

Recombinant human growth hormone (rhGH) therapy is used in the long-term treatment of children with growth disorders, but there is considerable treatment response variability. The exon 3-deleted growth hormone receptor polymorphism (GHR(d3)) may account for some of this variability. The authors performed a systematic review (to April 2011), including investigator-only data, to quantify the effects of the GHR(fl-d3) and GHR(d3-d3) genotypes on rhGH therapy response and used a recently established Bayesian inheritance model-free approach to meta-analyze the data. The primary outcome was the 1-year change-in-height standard-deviation score for the 2 genotypes. Eighteen data sets from 12 studies (1,527 children) were included. After several prior assumptions were tested, the most appropriate inheritance model was codominant (posterior probability = 0.93). Compared with noncarriers, carriers had median differences in 1-year change-in-height standard-deviation score of 0.09 (95% credible interval (CrI): 0.01, 0.17) for GHR(fl-d3) and of 0.14 (95% CrI: 0.02, 0.26) for GHR(d3-d3). However, the between-study standard deviation of 0.18 (95% CrI: 0.10, 0.33) was considerable. The authors tested by meta-regression for potential modifiers and found no substantial influence. They conclude that 1) the GHR(d3) polymorphism inheritance is codominant, contrasting with previous reports; 2) GHR(d3) genotypes account for modest increases in rhGH effects in children; and 3) considerable unexplained variability in responsiveness remains.     

Taste preferences in human obesity: environmental and familial factors

Taste-response profiles influence food selection and may help distinguish among potential subgroups of obese individuals. A representative community-based sample of 61 obese and 31 lean adults tasted five sucrose solutions and nine fat-containing solid stimuli resembling cake icings. Solid stimuli contained 15-35% fat and 20-70% sucrose (by weight). No significant differences in taste responsiveness were observed between obese and lean groups. Obese subjects were then divided into subgroups based on age at onset of obesity and past fluctuations in body weight. Obese subjects characterized by large weight fluctuations showed elevated preferences for sugar and fat mixtures compared with the stable subgroup. In contrast, early age at onset of obesity (less than 10 y), thought to be a measure of familial risk, had no significant effects on taste preferences. Environmental as opposed to familial factors may be more immediate determinants of taste preferences and food choice.     

Childhood obesity and human capital accumulation

The prevalence of childhood obesity has tripled in the United States over the last 25 years, and in addition to increased risks of many chronic diseases, obesity may also be linked to lower skill attainment, poor social competency, and poorer labor outcomes. Any causal links between obesity and human capital accumulation could have important consequences for both health and economic well-being over the life course. We investigate the association of obesity and cognitive and non-cognitive outcomes among US children and adolescents aged 5 to 19 using the Child Development Supplement of the Panel Survey of Income Dynamics. We perform OLS and individual fixed effects regressions to address unobserved time invariant heterogeneity in the relationship between overweight/obesity and abilities. Results provide limited support for the hypothesis that obesity negatively affects non-cognitive but not cognitive outcomes and suggest that discrimination rather than a biological mechanism contributes to negative outcomes found in the literature on adults.     

Characterizing daily urinary hormone profiles for women at midlife using functional data analysis

The availability of daily hormone values for entire menstrual cycles offers an opportunity to apply new analytic techniques that confirm current knowledge and provide new insights into patterns of changing hormone profiles in women as they transition to the menopause. The Study of Women's Health Across the Nation (SWAN) collected urine samples during 1997-1999 from one menstrual cycle or up to 50 days from 848 women who live in seven cities across the United States. These samples were assayed for the urinary forms of estrogen, progesterone, follicle-stimulating hormone, and luteinizing hormone. The authors used functional data analysis to study variability in the hormone patterns of 572 of the 848 pre- and early-perimenopausal women with evidence of a luteal transition. Functional data analysis enabled the authors to identify asymmetries in women's hormone patterns related to cycle length that are not captured with single hormone value comparisons. Longer cycles were characterized by increasing dyssynchrony between follicle-stimulating hormone and luteinizing hormone in the luteal phase.