PubMed Health⌕ Search

Biomedical subjects

U Pagotto

Publications and source records attributed to U Pagotto.

At least 19 recordsLinked to original sources
PubMed2007

Acyl ghrelin and metabolic hormones in pregnant and lactating sows.

Ghrelin, the endogenous ligand of the growth hormone (GH) secretagogue receptor, is considered a pleiotropic regulator involved in a large array of functions, including control of energy balance, regulation of food intake and, more recently, modulation of the reproductive axis. The present study was aimed at determining the changes in plasma concentrations of acyl-ghrelin in pregnant and lactating sows, with special emphasis on the relationship with the levels of GH, leptin, non-esterified fatty acids (NEFA) and insulin-like growth factor (IGF-1). Blood samples were collected via jugular venipuncture from 22 multiparous sow 30, 60 and 90 days after artificial insemination, 7 and 21 days after farrowing and at first oestrus post-weaning. Plasma concentrations of acyl-ghrelin, leptin, GH and IGF-1 were quantified by validated radioimmunoassay; NEFA were determined using a colorimetric procedure. Plasma acyl ghrelin levels were highest at 30 days of pregnancy and decreased thereafter and during lactation. At the beginning of lactation, GH, IGF-1 and NEFA concentrations significantly increased, while a significant reduction occurred in leptin. In conclusion, ghrelin concentrations in sow maternal circulation does not seem to play an important role in maintaining circulating GH levels during lactation; moreover, ghrelin is not associated with leptin, NEFA and IGF-1 levels.

Animals↗
PubMed2006

The impact of obesity on reproduction in women with polycystic ovary syndrome.

The polycystic ovary syndrome (PCOS) is one of the most common causes of infertility due to anovulation in women. The clinical features of PCOS are heterogeneous and may change throughout the lifespan, starting from adolescence to postmenopausal age. This is largely dependent on the influence of obesity and metabolic alterations, including an insulin-resistant state and the metabolic syndrome, which consistently affect most women with PCOS. Obesity does in fact have profound effects on both the pathophysiology and the clinical manifestation of PCOS, by different mechanisms leading to androgen excess and increased free androgen availability and to alterations of granulosa cell function and follicle development. Notably, simple obesity per se represents a functional hyperandrogenic state. These mechanisms involve early hormonal and metabolic factors during intrauterine life, leptin, insulin and the insulin growth factor system and, potentially, the endocannabinoid system. Compared with normal weight women with PCOS, those with obesity are characterised by a worsened hyperandrogenic and metabolic state, poorer menses and ovulatory performance and, ultimately, poorer pregnancy rates. The importance of obesity in the pathogenesis of PCOS is emphasised by the efficacy of lifestyle intervention and weight loss, not only on metabolic alterations but also on hyperandrogenism, ovulation and fertility. The increasing prevalence of obesity among adolescent and young women with PCOS may partly depend on the increasing worldwide epidemic of obesity, although this hypothesis should be supported by long-term prospective epidemiological trials. This may have great relevance in preventive medicine and offer the opportunity to expand our still limited knowledge of the genetic and environmental background favouring the development of the PCOS.

Adipose Tissue↗
PubMed2006

Central obestatin administration does not modify either spontaneous or ghrelin-induced food intake in rats.

The isolation of ghrelin unveiled a new system implicated in food intake regulation. The recently isolated hormone obestatin derives from the same precursor of ghrelin and seems to perform opposite actions. It could be part of a dual system connecting gut and brain to regulate energy homeostasis. The ability of intracerebroventricular administration of obestatin to modify food intake was evaluated. Obestatin had no effect on spontaneous food intake in both ad libitum and food restricted rats. The obestatin injection was not able to antagonize the ghrelin-stimulated increase in food intake either. In conclusion, the present work does not support a role for obestatin on the regulation of food intake in any model studied.

Animals↗
PubMed2006

How many sites of action for endocannabinoids to control energy metabolism?

The promising results obtained by clinical trials using Rimonabant to tackle visceral obesity and related disorders recently promoted a remarkable impulse to carry out detailed investigations into the mechanisms of action of endocannabinoids in regulating food intake and energy metabolism. The endocannabinoid system has been known for many years to play an important role in the modulation of the neuronal pathways mediating the rewarding properties of food. However, in the last few years, with the advanced understanding of the crucial role of the hypothalamic neuronal network in the regulation of appetite, several studies have also directed attention to the orexigenic role of the endocannabinoid system, substantiating the well known appetite stimulating properties of derivatives of Cannabis sativa. Furthermore, the last 2 years have seen a number of relevant publications emphasizing the role of endocannabinoids as significant players in various peripheral metabolic processes. To date, the roles of the endocannabinoid system in influencing energy metabolism have proved to be more complex than was formerly believed. However, the diverse ability to modulate both central and peripheral processes highlights the pivotal involvement of the endocannabinoid system in the control of metabolic processes. This review describes the roles of endocannabinoids and the cannabinoid type 1 receptor (CB1) in the control of energy balance.

Adipose Tissue↗
PubMed2006

Somatostatin receptor subtypes mediate contractility on human colonic smooth muscle cells.

This study demonstrates the expression of functional somatostatin receptor (sstr) subtypes in human circular and longitudinal colonic smooth muscle cells (SMC). Native somatostatin (SS) and sstr subtype-specific analogues were used to characterize the sstr subtypes present in both cell types by contraction/relaxation studies. Qualitative and quantitative mRNA analysis and immunohistochemistry of sstr subtypes were also carried out. sstr subtype 2 mRNA was expressed in circular SMC, and various levels of subtypes 1, 2 and 3 mRNA were expressed in longitudinal colonic SMC. Native SS and each subtype-specific analogue exerted a modest, but significant, contraction, although inhibition of carbachol-induced contraction (relaxation) was the main effect on SMC from both layers. CH-288, a sstr subtype 1-specific analogue, and octreotide, a sstr subtype 2-specific analogue, were the most effective relaxant analogues on longitudinal and circular SMC, respectively. sstr subtypes display a distinct expression pattern on human colonic SMC; on circular SMC, subtype 2 is the only sstr, whereas sstr subtypes 1, 2 and 3 are expressed on human SMC isolated from the longitudinal layer. The contractile effects of SS are mediated through sstr subtype 2 and sstr subtype 1 on circular and longitudinal human colonic SMC, respectively.

Cells, Cultured↗
PubMed2006

Endocannabinoids and energy metabolism.

Although adjustments to nutritional lifestyle and increased physical activity remain the milestones of weight loss therapy, it is evident from the exponential increase of the number of obese subjects in Western countries that these two approaches alone are no longer able to limit this progression. This alarming phenomenon occurs in spite of a great effort exerted in the last 10 yr to shed light on the pathogenetic mechanisms inducing obesity, although many inconclusive hopes have been generated in the field of pharmacotherapeutics to tackle obesity. Among the several targets exploited in recent years, the endocannabinoid system nowadays constitutes the most promising and the most intriguing proposed so far. On one hand, our aim is to provide an overview on the role of the endocannabinoid system in the physiology of energy metabolism, on the other hand a further aim is to summarize how the system also controls food intake and energy balance by acting at both cerebral and peripheral level.

Animals↗
PubMed2005

Short-term modification of sex hormones is associated with changes in ghrelin circulating levels in healthy normal-weight men.

The aim of this study was to evaluate the effect of selective and short-term sex hormone modifications on ghrelin levels in normal-weight eugonadal men undergoing hormonal contraceptive treatments. Seven men received an oral progestin [cyproterone acetate (CPA) or dienogest (DNG)] 10 mg/day for 3 weeks (CPA-DNG group), 7 CPA orally 5 mg/day in association with testosterone enanthate (TE) im 200 mg/week for 8 weeks (CPA-TE group), and 7 placebo (PLAC) for 8 weeks (PLAC group). Anthropometry and blood levels of LH, FSH, testosterone, estradiol, glucose, insulin and total ghrelin were evaluated. At baseline, no parameters differed among the three groups. After treatment, LH and FSH decreased in both CPA-DNG and CPA-TE groups, whereas they did not change in the PLAC group. Testosterone and estradiol decreased in the CPA-DNG group to the hypogonadal range, increased in the CPA-TE group to supraphysiological concentrations and, as expected, remained unchanged in the PLAC group. Total ghrelin levels increased in the CPA-DNG, decreased in the CPA-TE and did not change in the PLAC group. Ns modifications in the other parameters were observed in any group, demonstrating that the short-term changes of circulating sex hormones are able to modify ghrelin levels. These data, therefore, suggest that sex steroids are important regulators of ghrelin in normal-weight healthy men too.

Adult↗
PubMed2005

Gastric immunolocalization and plasma profiles of acyl-ghrelin in fasted and fasted-refed prepuberal gilts.

Ghrelin is a peripheral circulating hormone, mainly released from the stomach, which can stimulate food intake. We studied fed, fasted and fasted-refed prepuberal gilts in order to outline possible changes in gastric mucosal ghrelin cells and in plasma ghrelin profiles in response to food deprivation. Acyl-ghrelin-immunoreactive cells were numerous in oxyntic glands, less abundant in cardiac glands and least frequent in pyloric glands, with the addition of a minor population of labelled cells in the gastric pit mucosa. When fed and fasted animals were compared (72-h fast versus fed; n = 4 each), no clear-cut differences were revealed in labelled cell numbers, nor in their staining intensity. An RIA for plasma porcine acyl-ghrelin (n-octanoylated at Ser-3), not recognizing des-acyl-ghrelin, was validated. Plasma acyl-ghrelin progressively increased upon fasting (over 6, 12, 24 and 48 h); ghrelin levels significantly (P<0.05) higher than those prefast were reached at 72 h. After refeeding, plasma ghrelin was rapidly restored to basal values by 6 h. In the same animals, plasma insulin was significantly reduced throughout the fasting period (6-72 h), while rapidly increasing after refeeding. Non-esterified fatty acid levels increased during fasting (12-72 h) and rapidly returned to low values after refeeding. In conclusion, the present study demonstrates that starvation and refeeding influence ghrelin plasma level in prepuberal gilts. The absence of detectable changes in ghrelin cells, as seen in immunohistochemistry, could be due to a large intracellular storage of potentially releasable acylghrelin.

Animals↗
PubMed2005

Metabolic alterations and cardiovascular risk factors in the polycystic ovary syndrome.

Available literature indicates that polycystic ovary syndrome (PCOS) represents a condition with a high prevalence of the metabolic syndrome, a greater and precocious appearance of glucose intolerance states, including type 2 diabetes mellitus, and a potentially greater risk for cardiovascular diseases. With respect to metabolic disorders, however, there is also emerging evidence that they are more prevalent in PCOS rather than in the general population, and that there are regional differences in the world, depending on lifestyle and other environmental factors. This evidence should be taken into consideration in future strategies focusing on prevention of metabolic and cardiovascular disorders in PCOS, not only on treatment of infertility and signs of androgen excess.

Cardiovascular Diseases↗
PubMed2004

Response of the hypothalamic-pituitary-adrenal axis to small dose arginine-vasopressin and daily urinary free cortisol before and after alprazolam pre-treatment differs in obesity.

OBJECTIVE: Arginine vasopressin (AVP) has a central role in the response of the hypothalamic-pituitary-adrenal (HPA) axis to stress conditions. A low dose of AVP has been shown to have a modest, but significant effect on ACTH response in normal weight subjects. The aim of this study was to test the response of the HPA axis in obese subjects in order to assess eventual primary neuroendocrine alterations, previously demonstrated by using AVP combined with corticotropin releasing hormone (CRH). In addition, given its central inhibitory action on the HPA axis, we investigated whether the suppressive capacity of alprazolam (APZ) pretreatment on the hormone response to low-dose AVP challenge and daily urinary free cortisol (UFC) excretion rate may be altered in the presence of obesity. DESIGN: Fifteen overweight or obese women and eight normal-weight controls randomly underwent two low-dose AVP tests (0.3 UI iv bolus), one without (AVP test) and the other preceded by APZ administration (0.5 mg at midnight and 0.5 mg 90 min before the test in the morning at 08:30 h) (APZ/AVP test). Blood samples for ACTH and cortisol assay were obtained at baseline and throughout each test. The day before each test, 24h-UFC/ creatinine was also mea-sured. RESULTS: Basal ACTH levels were similar in the two groups, whereas cortisol concentrations were significantly lower in the overweight/obese group. Overweight/obese women had higher ACTH and cortisol responses to the AVP tests and significantly greater hormone inhibition after APZ than controls. In both groups, AVP-induced delta-peak cortisol values before and after APZ pre-treatment were significantly correlated. Body fat distribution had no effect on the HPA axis response to AVP either before or after APZ. Moreover, APZ decreased 24h-UFC/creatinine values unsignificantly in controls and by approximately 50% in the overweight/obese subjects. These changes were unrelated to the cortisol response to the AVP test before and after APZ pretreatment. On the other hand, percent changes of 24h-UFC/creatinine after APZ were negatively related to the body mass index (BMI) but positively with waist circumference values, which indicates that the abdominal obesity phenotype may counteract the 24 h-UFC/creatinine that would be expected on the basis of BMI values. CONCLUSIONS: Our data further support the concept that in women obesity may represent a condition of hyperresponsiveness or hypersensitivity of the HPA axis to neuroendocrine stimuli, which appear to be independent of feedback control. In addition, the data on the inhibiting capacity of APZ on UFC excretion confirm that the alterations of the HPA axis in obesity is particularly evident in the abdominal phenotype.

Adult↗
PubMed2004

Differential expression of menin in sporadic pituitary adenomas.

Pituitary adenomas represent one of the key features of multiple endocrine neoplasia type 1. The gene involved in this syndrome (MEN1) is a putative tumor suppressor, that codes for a 610-amino acid nuclear protein termed 'menin'. Analyses of sporadic pituitary adenomas have so far failed to reveal MEN1 mutations or defects in MEN1 transcription in these tumors. In the present study we detected menin protein expression in a panel of normal and tumoral pituitary tissues, using a monoclonal antibody against the carboxy-terminus of menin. In the normal human pituitary gland, strong nuclear staining for menin was detectable in the majority of the endocrine cells of the anterior lobe, without a clear association with a particular hormone-producing type. In sporadic pituitary adenomas, menin expression was variable, with a high percentage of cases demonstrating a significant decrease in menin immunoreactivity when compared with the normal pituitary. Interestingly, metastatic tissues derived from one pituitary carcinoma had no detectable menin levels. Altogether, our data provide the first information regarding the status of menin expression in human normal and neoplastic pituitary as determined by immunohistochemistry (IHC).

Adenoma↗
PubMed2004

Expression of epidermal growth factor receptor in neoplastic pituitary cells: evidence for a role in corticotropinoma cells.

The oncogenic effects of epidermal growth factor (EGF) have long been established. EGF receptor (EGFr) is overexpressed in many types of tumors and constitutes a target for cancer treatment. The pituitary gland is a target of EGF action and it is very likely that EGFr plays a role in pituitary tumor formation and progression. However, there is a controversy in the literature concerning EGFr expression in the different types of pituitary adenomas. In the present study we investigated the expression pattern of the wild type EGFr (EGFrWT) and the constitutively active variant III (EGFrvIII) at the mRNA and protein levels in a large series of pituitary tumors. EGFrWT was found in a high percentage of hormone-secreting tumors, but only in a small fraction of non-functioning pituitary adenomas, while no expression of the EGFrvIII could be detected by nested RT-PCR in any tumor. Among the hormone-secreting adenomas, the highest incidence of EGFr expression was found in Cushing's pituitary adenomas. Furthermore, immunohistochemistry for the phosphorylated EGFr revealed the presence of activated EGFr in most Cushing's adenomas, compared with most pituitary adenomas. Taking into account that downregulation of p27/Kip1 plays a significant role in corticotrope tumorigenesis and that EGFr mitogenic signaling results in decreased p27/Kip1, we searched for a correlation between EGFr expression and p27/Kip1 levels in corticotropinomas. Low p27/Kip1 immunoreactivity was observed in corticotropinomas expressing EGFr. On the other hand, somatotropinomas expressing EGFr had high p27/Kip1 immunoreactivity. These data suggest a corticotrope-specific phenomenon and indicate that EGFr may have a role in the unbalanced growth of corticotrope tumoral cells.

Adenoma↗
PubMed2003

Anti-androgen treatment increases circulating ghrelin levels in obese women with polycystic ovary syndrome.

In a previous study we were the first to describe a negative correlation between circulating ghrelin concentrations and androgen levels in human plasma, suggesting an interaction between ghrelin and the endocrine regulation of reproductive physiology. We now investigated a potential direct regulatory influence of circulating androgens on plasma ghrelin levels. Fourteen obese women with polycystic ovary syndrome (PCOS) on a hypocaloric diet were randomly assigned to treatment groups (open-labeled design), receiving either placebo (no.=7) or the antiandrogen flutamide (no.=7) for 6 months. Anthropometry, visceral (VAT) and subcutaneous (SAT) adipose tissue (quantified by computerized tomography), plasma hormone levels, insulin sensitivity indexes (Quantitative Insulin-Sensitivity Check Index-QUICKI) and Homeostatic Model Assessment applied to the oral glucose tolerance test (HOMA(OGTT)) were evaluated at baseline and at the end of the study. Body weight decreased and insulin resistance indexes improved in both groups. A tendency toward a greater loss of VAT was observed in the flutamide group. Only in the flutamide group was a significant reduction of androgens levels observed. Plasma ghrelin levels significantly increased following treatment with flutamide, while ghrelin remained unchanged in the placebo group. We observed a negative correlation between changes of ghrelin levels and changes of androgen plasma concentration in the flutamide-treated group. In the same group a positive correlation was found between plasma ghrelin changes and insulin sensitivity as expressed by HOMA(OGTT). Analysis in a multiple regression model, however, showed that plasma ghrelin changes were mainly due to changes of androgen levels rather than improved insulin sensitivity. We, therefore, conclude that androgens are independent modulators of circulating ghrelin concentrations.

Adult↗
PubMed2003

Endogenous cannabinoid system as a modulator of food intake.

The ability of Cannabis sativa (marijuana) to increase hunger has been noticed for centuries, although intensive research on its molecular mode of action started only after the characterization of its main psychoactive component Delta(9)-tetrahydrocannabinol in the late 1960s. Despite the public concern related to the abuse of marijuana and its derivatives, scientific studies have pointed to the therapeutic potentials of cannabinoid compounds and have highlighted their ability to stimulate appetite, especially for sweet and palatable food. Later, the discovery of specific receptors and their endogenous ligands (endocannabinoids) suggested the existence of an endogenous cannabinoid system, providing a physiological basis for biological effects induced by marijuana and other cannabinoids. Epidemiological reports describing the appetite-stimulating properties of cannabinoids and the recent insights into the molecular mechanisms underlying cannabinoid action have proposed a central role of the cannabinoid system in obesity. The aim of this review is to provide an extensive overview on the role of this neuromodulatory system in feeding behavior by summarizing the most relevant data obtained from human and animal studies and by elucidating the interactions of the cannabinoid system with the most important neuronal networks and metabolic pathways involved in the control of food intake. Finally, a critical evaluation of future potential therapeutical applications of cannabinoid antagonists in the therapy of obesity and eating disorders will be discussed.

Animals↗
PubMed2003

Low ghrelin concentrations in nonalcoholic fatty liver disease are related to insulin resistance.

Several physiological and pathophysiological conditions, including changes in body fat, food intake, and insulin resistance, are known to be associated with variations in plasma ghrelin concentrations. We tested the hypothesis that insulin resistance exerts a primary role by measuring ghrelin in 86 patients with nonalcoholic fatty liver disease (NAFLD), a condition in which insulin resistance is relatively independent of obesity. Compared with 40 matched healthy subjects, patients with NAFLD had similar glucose levels and higher plasma insulin and insulin resistance [homeostasis model assessment (HOMA)-R index] by over 60%. Ghrelin was reduced (mean +/- SD, 226 +/- 72 pmol/liter in NAFLD vs. 303 +/- 123 in controls; P < 0.0001). In relation to quartiles of body mass index, ghrelin progressively decreased in controls (P = 0.003), but not in patients (P = 0.926). In relation to quartiles of HOMA-R, ghrelin decreased in both groups, and significantly correlated with HOMA-R. After adjustment for age and sex, HOMA-R was the sole factor significantly associated with low ghrelin in the whole group (odds ratio, 5.79; 95% confidence interval, 2.62-12.81; P < 0.0001) and specifically in NAFLD (2.96; 1.12-7.79; P = 0.028). The study suggests that insulin resistance is a major factor controlling ghrelin levels in subjects with and without NAFLD.

Adult↗
PubMed2002

Obesity and the polycystic ovary syndrome.

The polycystic ovary syndrome (PCOS) is a condition characterized by hyperandrogenism and chronic oligo-anovulation. However, many features of the metabolic syndrome are inconsistently present in the majority of women with PCOS. Approximately 50% of PCOS women are overweight or obese and most of them have the abdominal phenotype. Obesity may play a pathogenetic role in the development of the syndrome in susceptible individuals. In fact, insulin possesses true gonadotrophic function and an increased insulin availability at the level of ovarian tissue may favour excess androgen synthesis. Obesity, particularly the abdominal phenotype, may be partly responsible for insulin resistance and associated hyperinsulinemia in women with PCOS. Therefore, obesity-related hyperinsulinemia may play a key role in favouring hyperandrogenism in these women. Other factors such as increased estrogen production rate, increased activity of the opioid system and of the hypothalamic-pituitary-adrenal axis, decreased sex hormone binding globulin synthesis and, possibly, high dietary lipid intake, may be additional mechanisms by which obesity favours the development of hyperandrogenism in PCOS. Irrespective of the pathogenetic mechanism involved, obese PCOS women have more severe hyperandrogenism and related clinical features (such as hirsutism, menstrual abnormalities and anovulation) than normal-weight PCOS women. This picture tends to be more pronounced in obese PCOS women with the abdominal phenotype. Body weight loss is associated with beneficial effects on hormones, metabolism and clinical features. A further clinical and endocrinological improvement can also be achieved by adding insulin-sensitizing agents and/or antiandrogens to weight reduction programmes. These obviously emphasize the role of obesity in the pathophysiology of PCOS.

Androgens↗
PubMed2002

The role of endothelins in the regulation of pituitary function.

The different members of the endothelin peptide family exhibit potent, long-lasting vasoconstrictive effects and thus play a central role in blood pressure regulation. However, endothelins have also been shown to modulate renal, cardiac and immune functions under physiological and pathophysiological conditions. In addition, endothelins are thought to be involved in the progression of some types of tumours. Soon after their discovery in 1988, it was shown that endothelins affect hormone release in the pituitary. Moreover, the intrapituitary production and expression of both endothelins and endothelin receptors have been described. This review summarises the present day knowledge concerning the expression and regulation of intrapituitary endothelins and their receptors. In addition, the effects of endothelins on hormone production by anterior, intermediate and posterior pituitary cell types are reviewed and their importance for pituitary physiology and pathophysiology is discussed.

Animals↗