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BACKGROUND: Despite the marked increase in cardiovascular risk factors in Spain in recent years, the prevalence and incidence of cardiovascular diseases have not risen as expected. Our objective is to examine the association between consumption of olive oil and the presence of cardiometabolic risk factors in the context of a large study representative of the Spanish population. SUBJECTS AND METHODS: A population-based, cross-sectional, cluster sampling study was conducted. The target population was the whole Spanish population. A total of 4572 individuals aged ≥ 18 years in 100 clusters (health centers) were randomly selected with a probability proportional to population size. The main outcome measures were clinical and demographic structured survey, lifestyle survey, physical examination (weight, height, body mass index, waist, hip and blood pressure) and oral glucose tolerance test (OGTT) (75 g). RESULTS: Around 90% of the Spanish population use olive oil, at least for dressing, and slightly fewer for cooking or frying. The preference for olive oil is related to age, educational level, alcohol intake, body mass index and serum glucose, insulin and lipids. People who consume olive oil (vs sunflower oil) had a lower risk of obesity (odds ratio (OR) = 0.62 (95% confidence interval (CI) = 0.41-0.93, P = 0.02)), impaired glucose regulation (OR = 0.49 (95% CI = 0.28-0.86, P = 0.04)), hypertriglyceridemia (OR = 0.53 (95% CI = 0.33-0.84, P = 0.03)) and low HDL cholesterol levels (OR = 0.40 (95% CI = 0.26-0.59, P = 0.0001)). CONCLUSIONS: The results show that consumption of olive oil has a beneficial effect on different cardiovascular risk factors, particularly in the presence of obesity, impaired glucose tolerance or a sedentary lifestyle. European Journal of Clinical Nutrition (2013) 67, 911-916; doi:10.1038/ejcn.2013.130; published online 17 July 2013 Keywords: olive oil; diabetes; impaired glucose regulation; obesity; population-based study; cardiovascular risk, INTRODUCTION The high rates of morbidity and mortality due to cardiovascular diseases represent one of the greatest social and health care problems in developed countries, as well as in many [...]

The intracellular mechanisms that mediate the modulatory effects of glucose on islet amyloid polypeptide (IAPP) were analyzed in cultured rat pancreatic islets (PIs). Rat PIs cultured with high concentrations of glucose exhibited elevated IAPP and insulin messenger RNAs compared to PIs cultured in basal concentrations of glucose. Furthermore, the regulation of IAPP levels in PIs was dependent on the intracellular metabolism of glucose including the regulatory effects of calcium and adenosine 3',5'-cyclic monophosphate.

Aims/hypothesis: The Di@bet.es Study is the first national study in Spain to examine the prevalence of diabetes and impaired glucose regulation. Methods: A population-based, cross-sectional, cluster sampling study was carried out, with target population being the entire Spanish population. Five thousand and seventy-two participants in 100 clusters (health centres or the equivalent in each region) were randomly selected with a probability proportional to population size. Participation rate was 55.8%. Study variables were a clinical and demographic structured survey, lifestyle survey, physical examination (weight, height, BMI, waist and hip circumference, blood pressure) and OGTT (75 g). Results: Almost 30% of the study population had some carbohydrate disturbance. The overall prevalence of diabetes mellitus adjusted for age and sex was 13.8% (95% CI 12.8, 14.7%), of which about half had unknown diabetes: 6.0% (95% CI 5.4, 6.7%). The age- and sex-adjusted prevalence rates of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined IFG-IGT were 3.4% (95% CI 2.9, 4.0%), 9.2% (95% CI 8.2, 10.2%) and 2.2% (95% CI 1.7, 2.7%), respectively. The prevalence of diabetes and impaired glucose regulation increased significantly with age ( p < 0.0001), and was higher in men than in women ( p < 0.001). Conclusions/interpretation: The Di@bet.es Study shows, for the first time, the prevalence rates of diabetes and impaired glucose regulation in a representative sample of the Spanish population. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the association between diabetes mellitus and health-related quality of life (HRQOL) controlled for several sociodemographic and anthropometric variables, in a representative sample of the Spanish population. Methods. A population based, cross-sectional, and cluster sampling study, with the entire Spanish population as the target population. Five thousand and forty-seven participants (2162/2885 men/women) answered the HRQOL short form 12-questionnaire (SF-12). The physical (PCS-12) and the mental component summary (MCS-12) scores were assessed. Subjects were divided into four groups according to carbohydrate metabolism status: normal, prediabetes, unknown diabetes (UNKDM), and known diabetes (KDM). Logistic regression analyses were conducted. Results. Mean PCS-12/MCS-12 values were 50.9 ±8.5/47.6 ±10.2, respectively. Men had higher scores than women in both PCS-12 (51.8 ±7.2 versus 50.3 ±9.2; P < 0.001) and MCS-12 (50.2 ±8.5 versus 45.5 ±10.8; P < 0.001). Increasing age and obesity were associated with a poorer PCS-12 score. In women lower PCS-12 and MCS-12 scores were associated with a higher level of glucose metabolism abnormality (prediabetes and diabetes), (P < 0.0001 for trend), but only the PCS-12 score was associated with altered glucose levels in men (P < 0.001 for trend). The Odds Ratio adjusted for age, body mass index (BMI) and educational level, for a PCS-12 score below the median was 1.62 (CI 95%: 1.2-2.19; P < 0.002) for men with KDM and 1.75 for women with KDM (CI 95%: 1.26-2.43; P < 0.001), respectively. Conclusion. Current study indicates that increasing levels of altered carbohydrate metabolism are accompanied by a trend towards decreasing quality of life, mainly in women, in a representative sample of Spanish population. [ABSTRACT FROM AUTHOR]

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Visfatin has shown to be increased in type 2 diabetes but to be unrelated to insulin sensitivity. We hypothesized that visfatin is associated with insulin secretion in humans. To this aim, a cross-sectional study was conducted in 118 nondiabetic men and 64 (35 men and 29 women) type 2 diabetic patients. Type 1 diabetic patients with long-standing disease (n = 58; 31 men and 27 women) were also studied. In nondiabetic subjects, circulating visfatin (enzyme immunoassay) was independently associated with insulin secretion (acute insulin response to glucose [AIRg] from intravenous glucose tolerance tests) but not with insulin sensitivity (S(i)) or other metabolic or anthropometric parameters, and AIRg alone explained 8% of visfatin variance (beta = -0.29, P = 0.001). Circulating visfatin was increased in type 2 diabetes (mean 18 [95% CI 16-21] vs. 15 ng/ml [13-17] for type 2 diabetic and nondiabetic subjects, respectively; P = 0.017, adjusted for sex, age, and BMI), although this association was largely attenuated after accounting for HbA(1c) (A1C). Finally, circulating visfatin was found to be increased in patients with long-standing type 1 diabetes, even after adjusting for A1C values (37 ng/ml [34-40]; P < 0.0001, adjusted for sex, age, BMI, and A1C compared with either type 2 diabetic or nondiabetic subjects). In summary, circulating visfatin is increased with progressive beta-cell deterioration. The study of the regulation and role of visfatin in diabetes merits further consideration. [ABSTRACT FROM AUTHOR]

IGF-binding protein (IGFBP)-related protein 1 (IGFBP-rP1) has been shown to bind both IGFs and insulin, albeit with low affinity, and to inhibit insulin signaling. We hypothesized that IGFBP-rP1 is associated with insulin resistance and components of the IGF system in humans. To this aim, a cross-sectional study was conducted in 113 nondiabetic and 43 type 2 diabetic men. Insulin sensitivity (insulin sensitivity index [S(i)] from intravenous glucose tolerance tests in nondiabetic subjects, or the rate constant for disappearance of glucose [K(ITT)] from insulin tolerance tests in type 2 diabetic subjects), circulating IGFBP-rP1 (from enzyme-linked immunosorbent assay), adiponectin (from radioimmunoassay), C-reactive protein (CRP; from immunoturbidimetry), soluble tumor necrosis factor receptor 2 (sTNFR2; from enzyme-amplified sensitivity immunoassay), and IGF system parameters (IGF-I, free IGF-I, and IGFBP-1 from immunoradiometric assay) were assessed in all subjects. Among nondiabetic men, those in the highest quartile for circulating IGFBP-rP1 exhibited decreased S(i) and adiponectin (both P < 0.01) as well as increased CRP and sTNFR2 (both P < 0.05). Circulating IGFBP-rP1 was also found to be increased in previously undiagnosed type 2 diabetic patients (P = 0.01) but not in known type 2 diabetic patients receiving pharmacological therapy. Although no changes in IGF system components were evident by IGFBP-rP1 quartiles in nondiabetic subjects, independent positive associations of IGFBP-rP1 with circulating fasting IGFBP-1 were evident after adjustment for insulin resistance parameters in both nondiabetic and type 2 diabetic subjects, with IGFBP-rP1 explaining 2 and 11% of IGFBP-1 variance, respectively. In additional multivariate analyses, S(i), sTNFR2, and age stood as independent predictive variables of IGFBP-rP1 (together explaining 18% of its variance) in nondiabetic subjects, and BMI became the only independent predictive variable of IGFBP-rP1 (explaining 26% of its variance) in type 2 diabetic men. These findings show for the first time that circulating IGFBP-rP1 is increased with insulin resistance, and they also suggest novel interactions between IGFBP-rP1 and the IGF system in humans. [ABSTRACT FROM AUTHOR]

Objective: There is growing evidence to indicate that somatostatin could be added to the list of natural antiangiogenic factors that exist in the vitreous fluid. In addition, a deficit of intravitreous somatostatin-like immunoreactivity (SLI) has been found in diabetic patients with proliferative diabetic retinopathy (PDR). In the present study, we have determined the main molecular variants of somatostatin (somatostatin-14 and somatostatin-28) in the vitreous fluid and plasma of nondiabetic control subjects and diabetic patients with PDR. In addition, the contribution of cortistatin, a neuropeptide with strong structural similarities to somatostatin, to SLI and its levels in vitreous and plasma in both nondiabetic and diabetic patients has also been measured. RESERCH DESIGN AND METHODS: Plasma and vitreous fluid from 22 diabetic patients with PDR and 22 nondiabetic control subjects were analyzed. Somatostatin-14, somatostatin-28 and cortistatin were measured by radioimmunoassay but separation by high-performance liquid chromatography was required to measure somatostatin-14.Results: The predominant molecular form of somatostatin within the vitreous fluid was somatostatin-28 (fivefold higher than somatostatin-14 in control subjects and threefold higher in patients with PDR). Cortistatin significantly contributed to SLI and its intravitreous levels were higher than those detected in plasma (nondiabetic control subjects: 147 [102-837] vs. 78 [24-32] pg/ml; patients with PDR: 187 [87-998] vs. 62 [24-472] pg/ml; P = 0.01 for both). Intravitreous somatostatin-14 was similar in both subjects with PDR and the control group (P = 0.87). By contrast, somatostatin-28 concentration was lower in patients with PDR than in nondiabetic control subjects (350 +/- 32 vs. 595 +/- 66 pg/ml; P = 0.004).Conclusions: Somatostatin-28 is the main molecular variant in the vitreous fluid. The intravitreous SLI deficit detected in patients with PDR is mainly due to somatostatin-28. Cortistatin is abundant in the vitreous fluid and significantly contributes to SLI. These findings could open up new strategies for PDR treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To study clinical characteristics, beta-cell function, HLA typing and mutations in the hepatocyte nuclear factor (HNF)-1alpha and HNF-4alpha genes in Type 1 diabetes mellitus (T1D) patients without pancreatic autoantibodies. DESIGN AND METHODS: Twenty patients without pancreatic autoantibodies (Ab neg) and 20 with autoantibodies (Ab pos), age/gender matched, were included (age 17-34 years). Islet cell, glutamic acid decarboxylase, tyrosine phosphatase and insulin autoantibodies, basal and stimulated C-peptide were measured. HLA-DRB1-DQA1-DQB1 typing and screening for mutations in the HNF-1alpha and HNF-4alpha genes were performed. RESULTS: No differences were found in clinical presentation, metabolic control and beta-cell function in the two groups (onset or after 12 months). DRB1*0301-DQA1*0501-DQB1*0201 was the most frequent haplotype in both groups but we found a higher proportion of protective T1D haplotypes and Asp(beta57) in the Ab neg group, but in all the cases in combination with susceptible T1D haplotypes. We found two previously reported polymorphisms (HNF-1alpha, Ala98Val; HNF-4alpha, Thr130Ile) in Ab neg and a new variant (Ser165Gly) in the HNF-4alpha gene in an Ab pos subject. Conclusions In a non-paediatric population with newly diagnosed T1D, the absence of islet antibodies does not imply clinical or metabolic differences when compared with those cases with islet antibodies. Despite a similar HLA-DR/DQ typing, the presence of protective alleles and molecular properties in a higher proportion in the Ab neg group suggests that these factors could modulate the presence or absence of islet antibodies. Variants in HNF-1alpha and HNF-4alpha are unlikely to be major contributors to the pathogenesis of diabetes in antibody-negative T1D. [ABSTRACT FROM AUTHOR]

To study clinical characteristics,β-cell function, HLA typing and mutations in the hepatocyte nuclear factor (HNF)-1α andHNF-4α genes in Type 1 diabetes mellitus (T1D) patients without pancreatic autoantibodies.Twenty patients without pancreatic autoantibodies (Ab neg) and 20 with autoantibodies (Ab pos), age/gender matched, were included (age 17–34 years). Islet cell, glutamic acid decarboxylase, tyrosine phosphatase and insulin autoantibodies, basal and stimulated C-peptide were measured. HLA-DRB1-DQA1-DQB1 typing and screening for mutations in theHNF-1α andHNF-4α genes were performed.No differences were found in clinical presentation, metabolic control andβ-cell function in the two groups (onset or after 12 months). DRB1*0301-DQA1*0501-DQB1*0201 was the most frequent haplotype in both groups but we found a higher proportion of protective T1D haplotypes and Aspβ57 in the Ab neg group, but in all the cases in combination with susceptible T1D haplotypes. We found two previously reported polymorphisms (HNF-1α, Ala98Val;HNF-4α, Thr130Ile) in Ab neg and a new variant (Ser165Gly) in theHNF-4α gene in an Ab pos subject.In a non-paediatric population with newly diagnosed T1D, the absence of islet antibodies does not imply clinical or metabolic differences when compared with those cases with islet antibodies. Despite a similar HLA-DR/DQ typing, the presence of protective alleles and molecular properties in a higher proportion in the Ab neg group suggests that these factors could modulate the presence or absence of islet antibodies. Variants in HNF-1α and HNF-4α are unlikely to be major contributors to the pathogenesis of diabetes in antibody-negative T1D.Diabet. Med. (2004) [ABSTRACT FROM AUTHOR]

Background: It has been recently suggested that gonadotrophin-releasing hormone agonist down-regulation in some normogonadotrophic women may result in profound suppression of LH concentrations, impairing adequate oestradiol synthesis and IVF and pregnancy outcome. The aims of this study, where receiver-operating characteristic (ROC) analysis was used, were: (i) to assess the usefulness of serum LH measurement on stimulation day 7 (S7) as a predictor of ovarian response, IVF outcome, implantation, and the outcome of pregnancy in patients treated with recombinant FSH under pituitary suppression; and (ii) to define the best threshold value, if any, to discriminate between women with 'low' or 'normal' LH concentrations.Methods: A total of 144 infertile women undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment were included. Seventy-two consecutive patients having a positive pregnancy test (including 58 ongoing pregnancies and 14 early pregnancy losses) were initially selected. As a control non-pregnant group, the next non-conception IVF/ICSI cycle after each conceptual cycle in our assisted reproduction programme was used.Results: The median and range of LH values in non-conception cycles, conception cycles, ongoing pregnancies, and early pregnancy losses, clearly overlapped. ROC analysis showed that serum LH concentration on S7 was unable to discriminate between conception and non-conception cycles (AUC(ROC) = 0.52; 95% CI: 0.44 to 0.61) or ongoing pregnancy versus early pregnancy loss groups (AUC(ROC) = 0.59; 95% CI: 0.46 to 0.70). To assess further the potential impact of suppressed concentrations of circulating LH during ovarian stimulation on the outcome of IVF/ICSI treatment, the three threshold values of mid-follicular serum LH proposed in the literature (<1, < or =0.7, <0.5 IU/l) to discriminate between women with 'low' or 'normal' LH were applied to our study population. No significant differences were found with respect to ovarian response, IVF/ICSI outcome, implantation, and the outcome of pregnancy between 'low' and 'normal' S7 LH women as defined by those threshold values.Conclusions: Our results do not support the need for additional exogenous LH supplementation in down-regulated women receiving a recombinant FSH-only preparation. [ABSTRACT FROM AUTHOR]

Background: Recent studies have indicated that the corpus luteum is a major source of circulating inhibin-A and serum concentrations of inhibin-A may reflect the human luteal function. The present prospective study was undertaken to determine the usefulness of mid-luteal serum concentrations of inhibin-A as markers of endometrial receptivity (as assessed by histological dating and alphavbeta3 integrin expression) and whether they are better predictors of endometrial function than serum progesterone.Methods: Consecutive infertile women (experimental group, n = 50) with regular menstrual cycles, and fertile women who were requesting contraception and had regular menstrual patterns and normal secretory endometria (control group, n = 10) were included. In all women basal body temperature, luteal serum concentrations of oestradiol, progesterone, prolactin, and inhibin-A, and endometrial biopsies were used in the same cycle to assess luteal function.Results: Out-of-phase mid-secretory endometria were detected in 17 of the 50 infertile women. Lack of alphavbeta3 integrin expression was detected in 27 of the 50 mid-luteal endometrial biopsies. Thus, hormonal concentrations were compared in the mid-luteal phase between the following eight groups of women: group 1 (n = 10), control fertile women; group 2 (n = 50), infertile women (all); subdivided into group 3 (n = 33), with in-phase biopsies; group 4 (n = 17), with out-of-phase endometria; group 5 (n = 23), expressing alphavbeta3 integrin in endometria; group 6 (n = 27), whose endometria did not express alphavbeta3 integrin; group 7 (n = 18), with both in-phase endometrial biopsy and alphavbeta3 integrin expression; and finally group 8 (n = 12), whose endometria were out-of-phase and did not express alphavbeta3 integrin. Mid-luteal serum concentrations of oestradiol, progesterone, prolactin, and inhibin-A of the seven infertile groups were similar to those of the control group of fertile women. No statistically significant difference between the infertile groups was observed for any hormonal parameter considered.Conclusion: Mid-luteal serum inhibin-A determination does not accurately reflect endometrial function/maturation and it is not a better indicator of endometrial luteal phase dysfunction than mid-luteal serum progesterone. [ABSTRACT FROM AUTHOR]

Background: Malnutrition seen in chronic alcoholics is partly due to reduced energy intake. Leptin is a peptide hormone implicated in the regulation of appetite and expenditure of energy. The prevalence and significance of abnormal circulating leptin levels in alcoholics, as well as the relationship of these levels with nutritional status, liver disease, and ethanol consumption, remain uncertain. Methods: Serum leptin levels were measured in 60 active asymptomatic alcoholics, 20 active alcoholics with cirrhosis of the liver, 20 abstinent alcoholics, and 60 controls. Nutritional status and ethanol consumption also were assessed. Results: In the control group, circulating leptin levels (mean 4.7 ± 0.3 μg/liter) correlated with body fat stores. Despite showing a lower fat area of the arm, active alcoholics had significantly higher leptin levels than the controls ( p < 0.001), regardless of the presence of cirrhosis. By contrast, none of the abstinent alcoholics showed hyperleptinemia. In the multivariate regression analysis, the fat area of the arm ( p < 0.001), the lifetime ethanol consumption ( p= 0.007), and the number of cigarettes smoked per day ( p= 0.02) were found to be independent factors that influenced leptin levels in active alcoholics. After we adjusted for age, fat area of the arm, and tobacco consumption, a significant correlation was observed between lifetime consumption of ethanol and serum leptin concentrations ( r= 0.36, p < 0.001). Conclusions: Circulating leptin levels are increased in a dose-dependent manner in chronic alcoholism, regardless of nutritional status or the presence of compensated liver disease. [ABSTRACT FROM AUTHOR]

Recent reports investigating the value of basal inhibin B determination as a predictor of ovarian reserve and assisted reproduction treatment have led to discordant results. This study was undertaken to further assess the relative power of day 3 inhibin B and follicle stimulating hormone (FSH) (defined before treatment) and the woman's age both as single and combined predictors of ovarian response and pregnancy in an in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) programme. A total of 120 women undergoing their first cycle of IVF or ICSI was included. Forty consecutive cycles cancelled because of poor follicular response were initially selected. As a control group, the nearest completed IVF/ICSI cycles before and after each cancelled cycle (i.e. the closest cycles in temporal relationship to the index cycle) were used. Mean age and basal FSH concentrations were significantly higher in the cancelled than in the control group (P: < 0.01 and P: < 0.001 respectively), whereas basal inhibin B was significantly higher in the latter (P: < 0.05). The association of basal FSH (with an accuracy or predictive value of ovarian response of 79%) with cancellation rate was significant, independent of, and stronger than the effects of age and inhibin B (P: < 0.05). Any two or all three of these variables studied did not improve the predictive value of FSH alone. Woman's age was the only variable independently associated with pregnancy rate. It is concluded that the stronger predictors of success in patients undergoing their first IVF/ICSI treatment cycle are age and basal FSH rather than inhibin B. Basal FSH concentration was a better predictor of cancellation rate than age, but age was a stronger predictor of pregnancy rate. [ABSTRACT FROM AUTHOR]

The present study investigates the usefulness of inhibin A, inhibin B and serum oestradiol concentrations obtained in the fifth day of gonadotrophin therapy in predicting ovarian response and assisted reproductive treatment outcome in women undergoing ovarian stimulation under pituitary desensitization. A total of 80 women undergoing their first cycle of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment were studied. Twenty consecutive cycles which were cancelled because of a poor follicular response were initially selected. As a control group, 60 women were randomly selected from our assisted reproductive treatment programme matching by race, age, body mass index, and indication for IVF/ICSI to those in the cancelled group. For each cancelled cycle, three IVF/ICSI women who met the matching criteria were included. Basal follicle stimulating hormone (FSH) concentrations were significantly higher in the cancelled than in the control group, whereas basal inhibin B was significantly higher in the latter. Basal oestradiol concentrations were similar in both groups of patients. On day 5 of gonadotrophin therapy serum concentrations of oestradiol, inhibin A and inhibin B were significantly lower in the cancelled group as compared with controls. Logistic regression analysis showed that the association for day 5 inhibin B (with a predictive value of ovarian response of 91.03%) with cancellation rate was significant, independent of, and stronger than, the effects of any other hormone variable investigated. In addition, day 5 inhibin B concentrations were correlated directly with parameters of ovarian response, ovum retrieval and oocyte and fertilization outcome. However, day 5 inhibin B was not a better predictor of pregnancy than the other hormone variables studied on this day. It is concluded that inhibin B concentrations obtained early in the follicular phase during ovarian stimulation under pituitary suppression for assisted reproductive treatment are highly predictive of ovarian response. [ABSTRACT FROM AUTHOR]

A growing body of information now supports the existence of a complete intraovarian insulin-like growth factor I (IGF-I) system. Although the precise role of IGF-I in the context of ovarian physiology remains to be determined, it is likely that IGF-I may engage in the amplification of gonadotrophin hormonal action. These facts and experiments with animals establishing the ovaries of multiple species as a site of growth hormone (GH) reception and action have led to the use of recombinant GH (rGH) as an adjunctive agent to potentiate ovulation induction by exogenous gonadotrophins. Whether intraovarian IGF-I plays an intermediary role in GH hormonal action at the ovarian level remains uncertain at present. The aim of this study was to evaluate whether rGH administration to pre-menopausal women could modify the expression of the IGF-I gene in the ovary. The expression of the IGF-I gene was examined in a time-dependent manner in normal pre-menopausal ovaries obtained from nine women treated with rGH and nine control women treated with placebo, using solution hybridization/RNase protection assays. Ovarian tissue samples were obtained 24 h (six women) and 7 days (12 women) following rGH/placebo injection. Total RNA (20 microg) from whole pre-menopausal ovaries (with or without rGH treatment) as well as from human granulosa cells was hybridized with a human IGF-I antisense RNA. IGF-I peptide, but not oestradiol, serum concentrations increased significantly 24 h after rGH injection. IGF-I gene, however, was not expressed in the luteinized granulosa cells and whole pre-menopausal ovaries irrespectively of rGH treatment in ovarian samples analysed both 1 and 7 days following rGH injection. On the contrary, IGF-II mRNA transcribed from the fetal or fetal-neonatal IGF-II promoter and IGF-I receptor mRNA (both used as hybridization control) were both found in whole pre-menopausal ovary and luteinized granulosa cells. Nevertheless, no changes in the hybridization patterns were seen in the absence or presence of rGH. These studies demonstrate that rGH administration to normal premenopausal women does not change the expression of insulin-like growth factors and their receptor genes in the pre-menopausal human ovary. Furthermore, these results provide further evidence against locally produced IGF-I as responsible for any ovarian effects seen in systemic rGH administration. [ABSTRACT FROM AUTHOR]

Marked granulosa cell proliferation along with important changes in the vascular bed of the ovary characterize IVF cycles associated with multiple follicular growth and maturation. The present report investigated follicular fluid (FF) and circulating concentrations of adrenomedullin, vascular endothelial growth factor (VEGF) and nitric oxide (NO) in 70 IVF patients (14 of whom became pregnant); these three vasoactive substances may be implicated in extensive ovarian tissue remodelling. Serum and FF concentrations of oestradiol and progesterone were also measured in the 70 IVF cycles studied. Follicular fluid concentrations of VEGF and adrenomedullin but not nitrite/nitrate (the two stable oxidation products of NO metabolism) were significantly higher (P < 0.0001) than the corresponding circulating concentrations. Follicular fluid concentrations of oestradiol and progesterone were not correlated with those of adrenomedullin, VEGF or nitrite/nitrate. No relationship existed between circulating concentrations of adrenomedullin, VEGF or nitrite/nitrate on the day of oocyte aspiration and parameters of ovarian response to gonadotrophin stimulation. In contrast, FF adrenomedullin concentration showed a direct relationship with day 3 FSH serum concentration (r = 0.53, P < 0.01) and the number of ampoules of gonadotrophin administered (r = 0.36, P < 0.005), but an inverse correlation with the total number of oocytes retrieved (r = -0.29, P < 0.01) and the number of mature oocytes (r = -0.25, P < 0. 05). A positive correlation was found for FF VEGF concentration and chronological age (r = 0.29, P < 0.05) and ampoules of gonadotrophins administered (r = 0.30, P < 0.05). There was no relationship between nitrite/nitrate FF concentrations and parameters of ovarian response. Neither serum concentrations nor FF concentrations of adrenomedullin, VEGF or nitrite/nitrate were correlated with IVF outcome. This study suggested for the first time that increased FF concentrations of adrenomedullin can be a marker of decreased ovarian response in IVF. Our results also provide further evidence favouring an association between FF VEGF and patient's age, while on the basis of our findings NO measurements are not a useful marker of ovarian response. [ABSTRACT FROM AUTHOR]