神经肽Y在惊厥性疾病患儿血浆和脑脊液中质量浓度变化及临床意义

目的观察血浆、脑脊液中神经肽Y(NPY)的质量浓度变化，探讨NPY在惊厥性疾病中的作用及临床意义。 方法选取2002 09—2003 08在陕西省人民医院儿科住院的惊厥性疾病患儿,采用放射免疫分析方法检测血浆和脑脊液中NPY的质量浓度。 结果(1)惊厥组血浆中NPY质量浓度第7天较第1天增高，差异有显著性(t=5366,P<001)，惊厥组各组第7天与第1天自身比较差异有显著性(t=3509,3480,3379,P<005)；脑炎无惊厥组第7天较第1天增高，但差异无显著性(t=1056,P=0309)；惊厥组与脑炎无惊厥组、对照组相比,差异有显著性(t=5728,P<001；t=6990,P<0001)，脑炎无惊厥组与对照组比较差异无显著性意义(t=0987,P>005)，惊厥组各组之间差异也有显著性(F=34674,P<001)。(2)惊厥组脑脊液中NPY质量浓度与脑炎无惊厥组、对照组比较差异有显著性(t=7830，5699，P<0001)，脑炎无惊厥组与对照组比较差异无显著性(t=0112，P=0911)，惊厥组各组之间差异也有显著性(F=68931，P<001)。(3)血浆和脑脊液中NPY质量浓度与惊厥发作次数有关(P<005),与性别、年龄、体重无显着相关，P均大于005;第1、7天血浆NPY质量浓度与第1天脑脊液NPY质量浓度有显着正相关性(r=0954，P<0001;r=0950，P<0001)。 结论(1)惊厥性疾病患儿血浆、脑脊液中NPY质量浓度均增高，与惊厥发作次数有关，但在惊厥发生的不同阶段质量浓度不同。(2)血浆与脑脊液中NPY质量浓度呈正相关性，血浆中的质量浓度能间接反映脑脊液质量浓度。提示动态监测NPY质量浓度可能有助于对惊厥的临床诊断、治疗及预后的判断。     

Body composition and concentrations of leptin, neuropeptide Y, beta-endorphin, growth hormone, insulin-like growth factor-I and insulin at menarche in girls with constitutional delay of puberty.

AIM: Constitutional delay of puberty (CDP), a rare condition among girls, manifests as retarded sexual maturity past the 13th year of life. The clinical and endocrinological aspects of this interesting problem appear to have escaped attention in the literature. The purpose of the present study was to compare body composition and concentrations of leptin, neuropeptide Y (NPY), beta-endorphin, growth hormone (GH), insulin growth factor-I (IGF-I) and insulin at menarche in CDP girls and girls with normal pubertal development (NP). MATERIALS AND METHODS: We enrolled 11 girls with CDP and 40 girls with NP. All participants were studied at or within 3 months of menarche. Age, height and weight were recorded. Body composition was established with a body composition analyzer. Radioimmunoassays were performed to measure concentrations of NPY, beta-endorphin, leptin, GH, IGF-I and insulin. RESULTS: The mean age at menarche in the CDP and NP groups was 16.1 and 12.5 years, respectively (p = 0.0001). CDP girls at menarche were taller (1.64 vs. 1.57 m; p = 0.012). The difference between groups in body weight (57.5 vs. 50.4 kg; p = 0.1), body mass index (BMI), fat mass, fat percentage (BF%) and lean mass was not significant, and nor was the difference in leptin, GH and insulin levels. However, CDP girls demonstrated significantly higher NPY concentrations (199.4+/-105.1 vs. 56.9+/-26.3 pg/ml; p = 0.001). NPY correlated with BF% (r = 0.60) in this group. IGF-I concentrations were significantly lower in CDP girls (524.8+/-50.6 ng/ml) than in NP girls (744.5+/-56.1 ng/ml; p = 0.024). CONCLUSION: Girls with CDP differed from NP girls only in age at menarche and height; they did not differ significantly with respect to BMI and body composition parameters. Higher concentrations of NPY in CDP girls may be responsible for CDP and reduced levels of IGF-I. Correlation of NPY with BF% suggests an involvement of this neuropeptide in the process of fat accumulation associated with CDP.     

Neuropeptide Y, leptin, galanin and insulin in women with polycystic ovary syndrome.

It has been reported that polycystic ovary syndrome (PCOS) is very frequently associated with obesity, insulin resistance and hyperinsulinemia. However, metabolic disorders may lead to suppression of reproductive hormone secretion during undernutrition and in obesity. Some neuropeptides, such as neuropeptide Y (NPY) and galanin, modulate the control of appetite and play an important role in the mechanism of luteinizing hormone-releasing hormone (LHRH) secretion. NPY and galanin regulate appetite via both central and peripheral mechanisms. The interaction between central and peripheral signals for the control of food intake is due to leptin. Leptin can modulate the activity of NPY and other peptides in the hypothalamus that are known to affect eating behavior. In order to evaluate the relationship between NPY, galanin and leptin, 28 women with PCOS, 32 obese women (non-PCOS) and 19 lean healthy women (control group) were investigated. Obese women with PCOS were divided into two groups: PCOS (A) overweight (body mass index, BMI 26-30 kg/m2), and PCOS (B) obese (BMI 31-40 kg/m2). Plasma NPY, galanin and leptin concentrations were measured by radioimmunoassay. Plasma leptin levels in obese women with PCOS (groups A and B) were significantly higher than those in the control group (p < 0.05, p < 0.05, respectively). A significant positive correlation between plasma leptin and BMI in women with PCOS was found (r = 0.427, p < 0.01). A positive correlation was demonstrated between leptin and testosterone in PCOS (r = 0.461, p < 0.01). Plasma galanin concentrations in PCOS were higher than in the control group but the differences were not significant. Plasma NPY levels were significantly elevated in both non-obese (normal) and obese women with PCOS (group A) (p < 0.01, p < 0.005, respectively). However, in obese non-PCOS women plasma NPY levels gradually increased with increase in BMI. No significant correlations were found between galanin, NPY and percentage change in response of LH to LHRH, as well as between NPY and insulin, and galanin and testosterone. Plasma insulin concentrations in women with PCOS (group B) were significantly higher than in the control group (p < 0.001). Increased plasma NPY levels are found in both obese and non-obese women with PCOS. The increase in NPY is independent of the increase in BMI. In obese women with PCOS, plasma leptin is increased compared with control lean women. Serum insulin concentration is increased in obese women with PCOS. A positive correlation exists between leptin and BMI as well as between leptin and testosterone in women with PCOS. These results may suggest that the feedback system in the interaction between leptin and NPY is disturbed in PCOS.     

妊高征患者血液中内皮细胞因子的表达

目的　探讨妊高征患者血液中内皮细胞因子的表达与妊高征发病和病情严重程度的关系。方法　1999年 1月至 2 0 0 1年 4月采用放射免疫法检测 6 5例不同组别的研究对象血浆中内皮细胞因子水平。结果　内皮素 1(ET 1)在重度妊高征组中显著升高 ,血管内皮生长因子 (VEGF)在各组间无差异 ,神经肽Y(NPY)在妊高征各组中较正常组升高 ,中、重度妊高征组降钙素基因肽 (CGRP)较正常组为低 ,胰岛素样生长因子 (IGF 1)在重度妊高征组显著低于正常组 ,胰岛素样生长因子结合蛋白 (IGFBP 3)水平在各组间差异无显著性意义。各细胞因子间关联性分析发现ET 1与VEGF、NPY及CGRP相关联 (r分别为 - 0 2 87P <0 0 5 ,0 2 6 5P <0 0 5 ,0 5 4 4P <0 0 1)。结论　ET 1和IGF 1在妊高征的发病机制中起重要的作用。ET 1与NPY呈正相关 ,提示妊高征的病理过程与ET 1及NPY等缩血管神经肽有关     

Structural imaging of the brain reveals decreased total brain and total gray matter volumes in obese but not in lean women with polycystic ovary syndrome compared to body mass index-matched counterparts

Purpose: To detect differences in global brain volumes and identify relations between brain volume and appetite-related hormones in women with polycystic ovary syndrome (PCOS) compared to body mass index-matched controls.

Methods: Forty subjects participated in this study. Cranial magnetic resonance imaging and measurements of fasting ghrelin, leptin and glucagon-like peptide 1 (GLP-1), as well as GLP-1 levels during mixed-meal tolerance test (MTT), were performed.

Results: Total brain volume and total gray matter volume (GMV) were decreased in obese PCOS compared to obese controls (p?p?p?Conclusion: This study, investigating structural brain alterations in PCOS, suggests volumetric reductions in global brain areas in obese women with PCOS. Functional studies with larger sample size are needed to determine physiopathological roles of these changes and potential effects of long-term medical management on brain structure of PCOS.     

Normal secretion of the incretin hormones glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 during gestational diabetes mellitus.

BACKGROUND AND AIM: Gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (DM2) are suggested to be caused by the same metabolic disorder. Defects in gut hormone-dependent regulation of beta-cell function (entero-insular axis) have been proposed to contribute to the pathogenesis of DM2. The aim of study was to evaluate whether an impaired secretion of glucagon-like peptide-1 (GLP-1) and/or glucose-dependent insulinotropic polypeptide (GIP) could play a role in the development of carbohydrate disorders during pregnancy. SUBJECTS AND METHODS: The study group (GDM) consisted of 13 gestational women with diabetes mellitus in whom GDM was diagnosed according to the World Health Organization criteria (75-g oral glucose tolerance test (OGTT)). The control group consisted of 13 pregnant women with normal glucose tolerance (NGT), matched according to age and duration of pregnancy. For all patients, plasma glucose, insulin, GLP-1 and GIP concentrations were evaluated after an OGTT, i.e. at 0, 30, 60, 90 and 120 min after glucose load. RESULTS: Fasting plasma glucose concentrations were similar in both groups, but the 0-120 min area under the curve (AUC) for glucose was significantly greater in the GDM group than in the NGT group (p < 0.0005). Fasting insulin concentration was higher (p < 0.05) and the 2-h insulin response (AUCtotal) was significantly greater (p = 0.01) in the GDM group than in the NGT group. Insulin resistance was significantly higher in GDM compared with control women (homeostasis model assessment, p = 0.003). Fasting GLP-1 concentrations were higher in the GDM group (p = 0.05), but no differences were observed in GLP-1 response (AUC) between the studied groups. Fasting and stimulated GIP response did not differ between groups at any time of the study (p > 0.05). Positive correlations were observed between fasting GLP-1 and insulin concentration (r = 0.56, p < 0.004) and between fasting GLP-1 and insulin resistance (r = 0.43, p < 0.029). CONCLUSION: An impaired secretion of GLP-1 and GIP does not seem to play a major role in the pathogenesis of GDM.     

Association between ghrelin levels and BMD: a cross sectional trial

Objective: Our aim was to determine whether the level of plasma total ghrelin varies with the menopause stage (pre-, peri-, and postmenopause). Participants and interventions: women were divided in three groups: premenopausal, perimenopausal and postmenopausal. All participants had bone mineral densitometry and blood assay of plasma ghrelin, estradiol E₂. Correlation between plasma ghrelin levels, their reproductive status and BMD was done. Results: The mean plasma level of ghrelin was significantly decreased in the perimenopausal and postmenopausal groups in comparison to the premenopausal group. A significant positive correlation was found between ghrelin and each of E₂ and BMD (at one or more of the three sites assessed) in all subjects, as well as, in peri- and postmenopausal women, whereas a significant negative correlation was found between ghrelin and FSH. Conclusion: It may be assumed that ghrelin can affect BMD. Whether ghrelin and estrogen work independent or through convergent mechanisms needs further studies.     

妊娠高血压综合征患者血浆神经肽Y水平变化的相关性研究

目的　探讨妊娠高血压综合征(妊高征)患者血浆神经肽Y(NPY)水平的变化及其与妊高征发病的关系。方法　采用放射免疫分析法测定了30例妊高征患者(妊高征组)产前及产后、23例正常妊娠妇女(正常妊娠组)和20例正常育龄未孕妇女(正常非孕组)血浆NPY水平。结果　妊高征组产前血浆NPY水平［(164.16±68.32)ng/L］明显高于正常非孕组［(86.60±20.65)ng/L］和正常妊娠组［(82.42±12.46)ng/L］(P<0.01)。妊高征组轻、中、重患者之间,产前血浆NPY水平有显著差异,分别为(88.66±25.69)ng/L、(145.15±18.72)ng/L、(235.05±33.60)ng/L(P<0.01)。妊高征组中、重度患者产前与产后血浆NPY水平分别为(80.04±28.70)ng/L及(130.43±37.38)ng/L,两者比较,差异有显著性(P<0.01);重度患者产后NPY水平仍明显高于正常妊娠组(P<0.01)。结论　妊高征患者血浆NPY水平增高,NPY参与了妊高征的发生和发展。     

Influence of obesity and menopausal status on serum leptin, cholecystokinin, galanin and neuropeptide Y levels.

Obesity occurs in 60% of women after menopause and is characterized by an excess of adipose tissue that depends on several orexigenic (neuropeptide Y (NPY) stimulates carbohydrate ingestion, galanin stimulates fat intake) and anorectic (leptin, cholecystokinin (CCK)) factors. Both leptin and insulin can reduce hypothalamic NPY production and secretion. Behavior related to the consumption of food is probably attributed to the NPY-galanin signalling route. We investigated basal levels of serum leptin, CCK, galanin and NPY in 16 non-obese premenopausal women, in 15 obese premenopausal women (body mass index (BMI) 34.6 +/- 1.3 SD) and in ten obese postmenopausal women (BMI 34.7 +/- 1.5 SD) to determine the relationship between obesity, menopause and these neuropeptides. Obese premenopausal women had three-fold elevations of serum leptin (32.1 +/- 3.2 ng/ml) in comparison to non-obese premenopausal women (10.3 +/- 1.5 ng/ml), but similar levels to those in obese postmenopausal women (35.3 +/- 4.1 ng/ml). In all 44 patients and in both sub-groups of premenopausal and postmenopausal women, serum leptin exhibited a strong positive correlation with BMI (r = 0.8692, p < 0.0001; r = 0.8803, p = 0.0001; r = 0.8184, p = 0.0001, respectively). Serum galanin values showed a statistically significant increment in the obese postmenopausal group (51.1 +/- 8.1 pg/ml) compared to both premenopausal groups: the non-obese (34.9 +/- 5.8 pg/ml) and the obese (36.0 +/- 5.5 pg/ml). Non-obese menstruating women demonstrated NPY levels (175.0 +/- 12.8 pg/ml) significantly higher than those of obese premenopausal women (126.0 +/- 12.1 pg/ml) and obese postmenopausal women (138.1 +/- 15.4 pg/ml). CCK values showed no differences between non-obese and obese pre- and postmenopausal groups. Basal insulin values were elevated in both obese groups compared to non-obese premenopausal women. Significantly increased leptin and galanin levels in postmenopausal obese women coupled with decreased NPY levels revealed some changes in the neuropeptides regulating eating behavior, which may be the reason for the onset of postmenopausal obesity.     

Serum ghrelin, leptin and resistin levels in adolescent girls with polycystic ovary syndrome

Aim:  The aim of the present study was to investigate the levels of leptin, resistin and ghrelin in polycystic ovary syndrome (PCOS), and to assess their possible correlations with the hormonal and metabolic features of PCOS.
Methods:  Sixteen obese (ObPCOS) and 12 lean (LeanPCOS) subjects with PCOS and 19 obese control subjects were enrolled in the study.
Results:  Ghrelin, leptin and resistin concentrations were similar between groups when body mass index (BMI) was used as a covariate ( P  > 0.05). Mean androgen, SHBG, luteinizing hormone (LH) levels and luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio tended to be similar between polycystic ovary syndrome (PCOS) groups. However, when compared with the control group, SHBG was lower and androgen, LH levels and LH/FSH ratio were higher in the PCOS groups. Free testosterone levels significantly correlated with resistin (r = −0.38), SHBG correlated significantly with body mass index (BMI) (r = −0.45) and resistin (r = −0.67), LH/FSH ratio was significantly correlated with ghrelin (r = −0.52) and estradiol (E2) levels (r = 0.51).
Conclusion:  ObPCOS and LeanPCOS groups having higher LH/FSH ratios and lower SHBG levels suggest that there could be factors other than adiposity responsible for the clinical features of PCOS patients. In the light of our results, those factors can be suggested as ghrelin and E2 for the elevated LH/FSH ratio and resistin for the lowered SHBG.     

Neurochemical and cellular markers in human cervix of late pregnant, postpartal and non-pregnant women

BACKGROUND: The aim was to evaluate the peptidergic innervation and the dendritic cell content in the cervix uteri. METHODS: Cervical biopsies were obtained from late pregnant (n=5), postpartal (n=5) and non-pregnant (n=5) women. The samples were prepared for immunohistochemistry using antibodies to protein S-100 (S-100), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), human peptide histidine isoleucine amide (PHM 27), neuropeptide tyrosine (NPY), and human histocompatibility complex class II subregion DR (HLA-DR). RESULTS: Nerve fibers positive for protein S-100, and dendritic cells positive for S-100 and HLA-DR were abundant in the cervix, especially at late pregnancy. CGRP, VIP, PHM-27 and NPY positive nerve fibers were present in non-pregnant, short nerve fibers and scattered immunoreactivity at term, and further scattered immunoreactivity after parturition. NPY positive nerve fibers were decreased at term, and after parturition a scattered immunoreactivity was observed. CONCLUSIONS: The abundant protein S-100 positive nerve fibers implies an impact of myelinated nerves in the cervix uteri during pregnancy. The abundant dendritic cells, positive for HLA-DR and S-100, especially at term, indicates a general activation of the immune system until late pregnancy and parturition. The changed occurrence and distribution of immunoreactivity for CGRP, VIP and PHM-27 suggest a release of these neuropeptides until term. The changes in NPY immunoreactivity indicate a release of NPY around parturition.     

Relationship of systemic hemodynamics, left ventricular structure and function, and plasma natriuretic peptide concentrations during pregnancy complicated by preeclampsia

OBJECTIVE: This study was done to evaluate left ventricular structure and function among pregnant patients with preeclampsia and compare them with those of normotensive pregnant and nonpregnant subjects. It also tested the hypothesis that abnormalities in left ventricular structure and function are associated with elevated plasma levels of natriuretic peptides. STUDY DESIGN: The study compared 75 pregnant women (n = 40 with preeclampsia; n = 35 normotensive pregnant women) and 10 nonpregnant normotensive control subjects undergoing an echocardiographic and biohumoral (renin activity and aldosterone, atrial natriuretic peptide, and brain natriuretic peptide concentrations) evaluation. The statistical analysis was carried out by analysis of variance, and significance was set at P <.05. RESULTS: Comparison of pregnant patients with preeclampsia versus both normotensive pregnant women and nonpregnant women showed significant increases in left ventricular mass and left ventricular endsystolic and end-diastolic volumes and significant reductions in left ventricular ejection fraction and percentage of fractional shortening. These changes coincided with increases in plasma levels of atrial natriuretic peptide and brain natriuretic peptide that were linearly related to the left ventricular structural and functional changes observed in patients with preeclampsia. CONCLUSION: Pregnant patients with preeclampsia showed adaptation to the increase in systemic blood pressure, with significant modification of left ventricular structure and function related to the plasma levels of both atrial natriuretic peptide and brain natriuretic peptide. A simple evaluation of plasma natriuretic peptide concentrations could help to discriminate patients with preeclampsia who have a condition of mild left ventricular overload.     

Normal secretion of the incretin hormones glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 during gestational diabetes mellitus

Background and aim. Gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (DM2) are suggested to be caused by the same metabolic disorder. Defects in gut hormone-dependent regulation of β-cell function (entero-insular axis) have been proposed to contribute to the pathogenesis of DM2. The aim of study was to evaluate whether an impaired secretion of glucagon-like peptide-1 (GLP-1) and/or glucose-dependent insulinotropic polypeptide (GIP) could play a role in the development of carbohydrate disorders during pregnancy.

Subjects and methods. The study group (GDM) consisted of 13 gestational women with diabetes mellitus in whom GDM was diagnosed according to the World Health Organization criteria (75-g oral glucose tolerance test (OGTT)). The control group consisted of 13 pregnant women with normal glucose tolerance (NGT), matched according to age and duration of pregnancy. For all patients, plasma glucose, insulin, GLP-1 and GIP concentrations were evaluated after an OGTT, i.e. at 0, 30, 60, 90 and 120 min after glucose load.

Results. Fasting plasma glucose concentrations were similar in both groups, but the 0–120 min area under the curve (AUC) for glucose was significantly greater in the GDM group than in the NGT group (p < 0.0005). Fasting insulin concentration was higher (p < 0.05) and the 2-h insulin response (AUC_total) was significantly greater (p = 0.01) in the GDM group than in the NGT group. Insulin resistance was significantly higher in GDM compared with control women (homeostasis model assessment, p = 0.003). Fasting GLP-1 concentrations were higher in the GDM group (p = 0.05), but no differences were observed in GLP-1 response (AUC) between the studied groups. Fasting and stimulated GIP response did not differ between groups at any time of the study (p > 0.05). Positive correlations were observed between fasting GLP-1 and insulin concentration (r = 0.56, p < 0.004) and between fasting GLP-1 and insulin resistance (r = 0.43, p < 0.029).

Conclusion. An impaired secretion of GLP-1 and GIP does not seem to play a major role in the pathogenesis of GDM.     

Circulating ghrelin levels and the polycystic ovary syndrome: correlation with the clinical, hormonal and metabolic features

Objectives

Dysregulation of ghrelin levels may lead to physiological problems including obesity and polycystic ovary syndrome (PCOS). The aim of the study was to compare ghrelin levels in women with and without PCOS.

Study design

Serum ghrelin levels (pre- and post-prandial) were compared between 30 Saudi women suffering from PCOS and 30 healthy controls. The relationship between circulating ghrelin levels and other hormones was investigated. Anthropometric measurements were made for all subjects. Biochemical and hormonal investigations included plasma glucose, insulin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17β-estradiol (E2), progesterone, testosterone and sex hormone binding globulin (SHGB), and serum ghrelin levels. The data were statistically analyzed using independent T-test and ANOVA. Correlation studies were performed between ghrelin levels and other variables.

Results

No differences were observed in the levels of ghrelin during fasting and the postprandial period in the PCOS (p = 0.487) and control groups (p = 0.378). A significant inverse correlation was observed in ghrelin levels (fasting and postprandial) levels and BMI (PCOS: r = −0.529; p = 0.009, controls: r = −0.670; p = 0.005); PCOS: r = −0.421; p = 0.007, controls: r = −0.491; p = 0.004 respectively). No correlations between ghrelin levels and other parameters were observed.

Conclusion

The findings of the study suggest that circulating plasma ghrelin levels were found to be normal and were inversely related to BMI in women with PCOS. No relationship between circulating ghrelin levels and the abnormal hormonal pattern of the PCOS were observed.     

The relationship between metabolic status and levels of adiponectin and ghrelin in lean women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is commonly associated with insulin resistance, obesity, dyslipidemia and hypertension. Adiponectin, an adipocyte-specific protein with important roles in glucose and lipid homeostasis, possesses antidiabetic and insulin-sensitizing properties. Ghrelin, a protein ligand for the growth hormone secretagog receptor, has been shown to stimulate food intake and to influence energy balance, insulin signaling and glucose metabolism. We aimed to evaluate the relationships between metabolic alterations and adiponectin and ghrelin levels in lean PCOS women, compared with lean and obese women. The study was carried out on 20 non-obese PCOS women aged 20 – 48 years and age-matched groups of 45 healthy lean and 37 obese women. Hormonal and biochemical parameters, adiponectin and ghrelin concentrations and anthropometric data were determined. In PCOS subjects, we found increased homeostasis model assessment – insulin resistance index (HOMA-IR) with non-significant differences in adiponectin and ghrelin concentrations compared with healthy women, although the PCOS group showed a tendency to lower adiponectin levels. However, ghrelin levels in PCOS women were significantly higher than in obese women. Moreover, we observed a negative correlation between adiponectin and testosterone, cholesterol, triglycerides, glucose and diastolic blood pressure in PCOS. In conclusion, it can be suggested that higher values of HOMA-IR with lower adiponectin levels may indicate future development of metabolic syndrome or other metabolic disturbances in lean PCOS women.     

The relationship between metabolic status and levels of adiponectin and ghrelin in lean women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is commonly associated with insulin resistance, obesity, dyslipidemia and hypertension. Adiponectin, an adipocyte-specific protein with important roles in glucose and lipid homeostasis, possesses antidiabetic and insulin-sensitizing properties. Ghrelin, a protein ligand for the growth hormone secretagog receptor, has been shown to stimulate food intake and to influence energy balance, insulin signaling and glucose metabolism. We aimed to evaluate the relationships between metabolic alterations and adiponectin and ghrelin levels in lean PCOS women, compared with lean and obese women. The study was carried out on 20 non-obese PCOS women aged 20 - 48 years and age-matched groups of 45 healthy lean and 37 obese women. Hormonal and biochemical parameters, adiponectin and ghrelin concentrations and anthropometric data were determined. In PCOS subjects, we found increased homeostasis model assessment - insulin resistance index (HOMA-IR) with non-significant differences in adiponectin and ghrelin concentrations compared with healthy women, although the PCOS group showed a tendency to lower adiponectin levels. However, ghrelin levels in PCOS women were significantly higher than in obese women. Moreover, we observed a negative correlation between adiponectin and testosterone, cholesterol, triglycerides, glucose and diastolic blood pressure in PCOS. In conclusion, it can be suggested that higher values of HOMA-IR with lower adiponectin levels may indicate future development of metabolic syndrome or other metabolic disturbances in lean PCOS women.     

Placental ghrelin and leptin expression and cord blood ghrelin,adiponectin, leptin,and C-peptide levels in severe maternal obesity

Purpose: The purpose of this study is to investigate placental ghrelin and leptin expression as well as cord blood ghrelin and adiponectin levels in maternal obesity and associations between placental ghrelin expression, cord blood ghrelin levels and maternal and infant variables.

Materials and methods: Placental ghrelin and leptin expression were analyzed by RT-PCR in 32 severely obese and 32 matched normal-weight women. Cord blood ghrelin, adiponectin, leptin, and C-peptide concentrations were analyzed by ELISA.

Results: Neither ghrelin nor leptin expression and neither cord blood ghrelin nor adiponectin levels differed between the groups. Placental ghrelin expression was associated with BMI at delivery in the obese women (r?=?0.424, p?=?.016) and in the infants born to normal-weight women with their weight z-scores at six (r?=??0.642, p?=?.010), nine (r?=??0.441, p?=?.015), and 12 months of age (r?=??0.402, p?=?.028).

Conclusions: Placental ghrelin and leptin expression as well as cord blood ghrelin and adiponectin levels do not seem to be altered in severe maternal obesity. Placenta-derived ghrelin may influence the infants’ postnatal weight gain, but possibly only when the mother has normal weight.     

Oral 17beta-estradiol and sequential progesterone in menopause: effects on insulin-like growth factors and their binding proteins.

OBJECTIVE: We evaluated the acute effects of low-dose oral estradiol and sequential progesterone on the insulin-like growth factor (IGF)/growth hormone (GH) axis, IGF-binding proteins (IGFBPs) 1 and 3, and plasma levels of sex hormone-binding globulin (SHBG) in postmenopausal subjects. STUDY DESIGN: Thirty healthy normal-weight women (mean age: 54.2 +/- 5.7 years) spontaneously postmenopausal for at least 6 months were enrolled. None had used hormone replacement therapy (HRT). Appropriate investigations excluded renal, glucose, lipid and coagulation abnormalities. Breast X-ray and endometrial ultrasound examinations excluded organic pathologies. They received oral cyclical HRT for 1 year, based on the administration of oral estradiol (1 mg/day) for 28 consecutive days plus progesterone (200 mg/day) from day 15 to day 28; out of the whole group, 15 subjects received progesterone orally (group A), while in 15 progesterone was administered transvaginally (group B). On the day before treatment (T0), on day 14 (T14) and on day 28 (T28) of the first cycle, plasma levels of estradiol, progesterone, SHBG, GH, IGF-I and -II, IGFBP-1 and -3, insulin and C-peptide were assayed in all patients. The same parameters were evaluated at T14 and T28 during the 12th month of treatment. RESULTS: At T14, we observed significant increases in the levels of estradiol (from 20 +/- 16 to 115 +/- 71 pg/ml, p < 0.001), SHBG (from 132 +/- 42 to 182 +/- 55 nmol/l, p < 0.001) and IGFBP-1 (from 92 +/- 57 to 127 +/- 87 ng/ml, p < 0.004), while the level of IGF-I decreased (from 197 +/- 138 to 129 +/- 85 ng/ml, p < 0.003). At T28, progesterone levels were significantly higher in the women receiving it orally than transvaginally (8.4 +/- 6.1 vs. 3.7 +/- 3.2 ng/ml, p < 0.025). However, while oral progesterone did not affect the estrogen-induced variations, transvaginal progesterone abrogated the increase in the levels of IGFBP-1. The levels of IGF-II, IGFBP-3, GH, glucose, C-peptide and insulin did not change at any time. At 1 year, the values maintained the same trends. The estrogen-induced variations of SHBG were correlated directly with those of estradiol (r = 0.48) and inversely with those of IGF-I (r = -0.424). CONCLUSIONS: Low-dose oral estradiol reduces plasma levels of IGF-I and increases IGFBP-1 and SHBG concentrations, while GH is unchanged. These effects, significant and immediate, lead us to hypothesize a direct action of estradiol on hepatocytes.     

Growth hormone and somatomedin-C secretion in patients with polycystic ovarian disease. Their relationships with hyperinsulinism and hyperandrogenism

Nineteen women with polycystic ovarian disease (PCO; 9 obese) and 15 normal ovulatory women (7 obese) were studied at their follicular phase. All patients had an oral glucose tolerance test (OGTT) before and after treatment with gonadotropin-releasing hormone (GnRH) agonist (Buserelin 400 micrograms/die s.c. for 8 weeks) to investigate the relationship between ovarian steroidogenesis and insulin and growth hormone (GH) and insulin-like growth factor (SmC) secretion. Luteinizing hormone, follicle-stimulating, estradiol, androstenedione, testosterone, dehydroepiandrosterone sulfate, cortisol, insulin, GH and SmC were measured basally at the time of OGTT. PCO patients showed higher androgen basal levels than control patients. All subjects showed a normal glycemic response to OGTT. The mean fasting level and area under the curve of plasma insulin were also significantly greater in PCO than in control patients (p less than 0.05), while GH and SmC plasma concentrations did not differ between the groups. Despite a considerable decrease in androgens and the similar levels in both PCO and control women, buserelin treatment did not determine any significant changes of insulin and GH-SmC secretion. GH and SmC did not correlate with ideal body weight (IBW), insulin or androgens, whereas insulin correlated with both testosterone and androstenedione levels (p less than 0.05) and with IBW (p less than 0.01); after the buserelin regimen only IBW remained related to plasma insulin (p less than 0.01). In conclusion results of this study confirm that hyperinsulinism is a characteristic picture of PCO and is related in an unclear way with hyperandrogenism and obesity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Body composition modulates the effects of hormone replacement therapy on growth hormone and insulin-like growth factor-I levels in postmenopausal women

OBJECTIVE: To examine the relationships of body composition with basal serum estrone, estradiol, androstenedione, cortisol, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels in 73 postmenopausal women. DESIGN: Cross-sectional study of hormone levels and body composition determined by dual-energy X-ray absorptiometry and anthropometry in women who were not taking oral hormone replacement therapy (HRT) and women taking HRT. Because high adiposity may modify hormone levels, subjects were grouped by fatness into obese (BMI >25 kg/m(2) and waist circumference >80 cm) and lean groups, as well as by HRT use. RESULTS: Total levels of estrone, estradiol, GH and cortisol were significantly higher and IGF-1 was lower in HRT users. In HRT users, estradiol levels were higher and GH levels were lower in obese than lean women. IGF-1 levels were lower in obese HRT users than lean nonusers. Total cortisol levels were significantly higher in lean HRT users than lean nonusers and obese users. GH and IGF-1 were significantly inversely correlated with trunk fat and percent body fat. Multiple regression revealed that only trunk fat was a significant (negative) determinant of GH and IGF-1 levels, whereas HRT use positively and negatively predicted GH and IGF-1, respectively. Percent body fat significantly predicted estradiol levels. Body composition did not differ by HRT use. CONCLUSIONS: Our results suggest that trunk fat attenuates the HRT-induced increase on GH levels. In addition, trunk fat is a significant determinant of low IGF-1 levels in postmenopausal women, and IGF-1 levels decline more with HRT use.