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Biomedical subjects

C S Mantzoros

Publications and source records attributed to C S Mantzoros.

At least 55 records · Page 3Linked to original sources
PubMed1998

Predictors of sex hormone levels among the elderly: a study in Greece.

This study examines the relationship between a series of epidemiologic parameters (age, height, body mass index (BMI), smoking, alcohol consumption, and coffee drinking) and serum concentrations of testosterone, estradiol, sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS). Among 52 healthy, elderly Greek men, we observed that serum levels of DHEAS decreased with increasing age [19% decline per 5-year increase in age, 95% CI, -2.1-(-33.5)], obesity [48% decline for BMI >30 kg/m2 compared to <27 kg/m2, CI, -15.7-(-68.7)], and current smoking [37% decline compared to nonsmokers, CI, -9.5-(-57.2)]. Estradiol concentrations increased with increasing BMI [77.1% increase for BMI >30 kg/m2 compared to <27 kg/m2, CI, -12.0-256.3], alcohol drinking [66% increase for > or = 7 glasses/week compared to <7 glasses/week, CI, 4.4-164.4], and coffee drinking [59% increase for > or = 14 cups/week compared to > or = 14 cups/ week, CI, -0.5-155.9], and decreased among current smokers [40% decline compared to nonsmokers, CI, -64.9-0.8]. SHBG was marginally positively associated with increasing age [13% increase per 5 years, CI, -0.5-29.6]. Testosterone was significantly related only to current smoking [27% decline compared to nonsmokers, CI, -45.4-(-3.1)]. These findings suggest that several variables appear to be associated with sex steroid levels and the influence of these findings on the occurrence of hormone-related conditions warrants further exploration.

Age Factors↗
PubMed1998

Leptin in relation to resumption of menses in women with anorexia nervosa.

Serum levels of leptin are decreased in underweight AN patients and increase with weight restoration. To assess the relationship of decreased leptin levels with other hormonal abnormalities in AN and to evaluate the possible role of increasing leptin levels, alone or in combination with other hormones, in the resumption of menses that accompanies weight gain, we studied cross-sectionally sixty-five consecutively enrolled AN patients. Subjects were divided in three groups: (I) underweight and amenorrheic; (II) weight-recovered but still amenorrheic; and (III) weight-recovered and eumenorrheic women. Patients in group I had decreased BMI, serum leptin, estradiol (E2), insulin-like growth factor 1 (IGF-1) and urinary growth hormone (GH) levels and increased sex hormone-binding globulin (SHBG) levels, compared to AN patients in groups II and III. Moreover, although no differences in leptin levels or BMI were observed between amenorrheic and eumenorrheic weight-recovered patients (groups II and III), free E2 and GH levels were higher (P<0.02) in weight-recovered, eumenorrheic women. Thus, it appears that leptin is a necessary, but not a sufficient, factor for the resumption of menses in AN patients.

Adult↗
PubMed1998

Zinc may regulate serum leptin concentrations in humans.

OBJECTIVE: Leptin, the product of the ob gene, plays a key role in a feedback loop that maintains energy balance by signaling the state of energy stores to the brain and by influencing the regulation of appetite and energy metabolism. Zinc also plays an important role in appetite regulation. Thus, we evaluated the relationship between zinc status and the leptin system in humans. METHODS: We studied nine healthy men with marginal zinc deficiency, induced by dietary means, before and after zinc supplementation. RESULTS: Zinc restriction decreased leptin levels while zinc supplementation of zinc-depleted subjects increased circulating leptin levels. In addition, zinc supplementation increased IL-2 and TNF-alpha production that could be responsible for the observed increase in leptin concentrations. CONCLUSIONS: Zinc may influence serum leptin levels, possibly by increasing the production of IL-2 and TNF-alpha.

Adult↗
PubMed1998

Gender differences in leptin levels during puberty are related to the subcutaneous fat depot and sex steroids.

Little is known about the influence of adiposity and hormone release on leptin levels in children and adolescents. We utilized criterion methods to examine the relationships among sex steroids, body composition (4 compartment), abdominal visceral and subcutaneous fat (magnetic resonance imagery), total subcutaneous fat (sum of 9 skinfolds), energy expenditure (doubly labeled water), aerobic fitness, and serum leptin levels in prepubertal and pubertal boys (n = 16; n = 13) and girls (n = 12; n = 15). The sum of skinfolds accounted for more variance in leptin levels of all girls [coefficient of determination (R2) = 0.70, P < 0.001] and all boys (R2 = 0.60, P < 0.001) than the total fat mass (girls, R2 = 0.52, P < 0.001; boys, R2 = 0.23, P < 0.001). Total energy expenditure, corrected for the influence of fat-free mass, correlated inversely with leptin (R2 = 0.18, P = 0.02). Gender differences in leptin disappeared when corrected for sex steroid levels or the combination of adiposity and energy expenditure. In multiple regression, the sum of skinfolds and free testosterone and estrogen levels accounted for 74% of the variance in leptin levels. We conclude that serum leptin levels are positively related to subcutaneous adiposity but negatively related to androgen levels. Energy expenditure may be negatively related to leptin levels by reduction of the adiposity, or a common genetic factor may influence both the activity and serum leptin levels.

Abdomen↗
PubMed1998

Severe leptin resistance in brown fat-deficient uncoupling protein promoter-driven diphtheria toxin A mice despite suppression of hypothalamic neuropeptide Y and circulating corticosterone concentrations.

Brown adipose tissue (BAT) has the capacity for uncoupled mitochondrial respiration and is proposed to be a key site for regulating energy expenditure in rodents. To better define the role of BAT in energy homeostasis, we previously created a line of transgenic mice with deficiency of BAT (UCP promoter-driven diphtheria toxin A transgenic mice [UCP-DTA]) mice. These mice develop obesity that initially is due to decreased energy expenditure and later accompanied by hyperphagia despite increased levels of circulating leptin. In addition, the obesity of these mice is accompanied by severe insulin-resistant diabetes and hyperlipidemia. To better define the basis for leptin resistance in this model, we treated UCP-DTA mice with leptin (300 microg i.p., b.i.d.) and compared their response with that of leptin-treated ob/ob and FVB control mice (30 microg i.p., b.i.d.). Leptin treatment of FVB and ob/ob mice decreased their body weight and food intake and improved their glucose homeostasis. In contrast, tenfold higher dosages of leptin had no effect on body weight, food intake, or circulating insulin or glucose concentrations of UCP-DTA mice. Hypothalamic neuropeptide Y (NPY) mRNA expression was lower in UCP-DTA mice than in littermate control FVB mice in the fed state, and increased progressively in response to food restriction as leptin levels fell. In parallel to the levels of hypothalamic NPY, corticosterone levels were initially suppressed and rose with food restriction. Thus food intake, body weight, and insulin and glucose homeostasis of UCP-DTA mice are all extraordinarily resistant to leptin, whereas hypothalamic NPY and the hypothalamopituitary adrenal (HPA) axis may remain under leptin control. Further elucidation of the mechanisms underlying leptin resistance in UCP-DTA mice may provide valuable insights into the basis for leptin resistance in human obesity.

Adipose Tissue, Brown↗
PubMed1998

Insulin-like growth factor-I in relation to premenopausal ductal carcinoma in situ of the breast.

We evaluated the association of plasma insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) with risk of breast cancer in a study of 94 cases of premenopausal ductal carcinoma in situ and 76 controls. Compared with women in the lowest tertile of IGF-I, women in the upper two tertiles of IGF-I had an elevated risk for ductal carcinoma in situ. Conversely, compared with women in the lowest tertile of IGFBP-3, women in the upper two tertiles of IGFBP-3 had a decreased risk for ductal carcinoma in situ. After grouping women on the basis of both IGF-I and IGFBP-3, women in the highest two tertiles of IGF-I and the lowest tertile of IGFBP-3 were at notably higher risk than women in the lowest tertile of IGF-I and the highest two tertiles of IGFBP-3 (odds ratio = 3.7; 95% confidence interval = 1.1-12.2). We conclude that the combination of high IGF-I and low IGFBP-3 may increase the risk of premenopausal ductal carcinoma in situ.

Adult↗
PubMed1997

Serum steroids in relation to prostate cancer risk in a case-control study (Greece).

Blood samples were collected from 52 incident cases of histologically confirmed prostate cancer and 52 age- and town of residence-matched healthy controls in Athens, Greece. Samples were analyzed blindly in Boston, Massachusetts (USA) for testosterone (T), estradiol (E2), sex hormone-binding globulin (SHBG), and dihydrotestosterone (DHT). The data were modeled using multiple logistic regression with adjustment for age, height, body mass index (wt/ht2), years of schooling, and mutually among hormones. DHT was associated inversely, significantly, and strongly with the risk of prostate cancer, whereas T was associated marginally positively, and E2 was associated nonsignificantly inversely with the disease. No association was observed in this study with respect to SHBG.

Aged↗
PubMed1997

Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia.

Blood samples were collected from 52 incident cases of histologically confirmed prostate cancer, an equal number of cases of benign prostatic hyperplasia (BPH) and an equal number of apparently healthy control subjects. The three groups were matched for age and town of residence in the greater Athens area. Steroid hormones, sex hormone-binding globulin, and insulin-like growth factor 1 (IGF-1) were measured in duplicate by radioimmunoassay in a specialized US centre. Statistical analyses were performed using multiple logistical regression. The results for IGF-1 in relation to prostate cancer and BPH were adjusted for demographic and anthropometric factors, as well as for the other measured hormones. There was no relation between IGF-1 and BPH, but increased values of this hormone were associated with increased risk of prostate cancer; an increment of 60 ng ml(-1) corresponded to an odds ratio of 1.91 with a 95% confidence interval of 1.00-3.73. There was also some evidence for an interaction between high levels of testosterone and IGF-1 in relation to prostate cancer. This finding suggests that, in addition to testosterone, IGF-1 may increase the risk of prostate cancer in humans.

Aged↗
PubMed1997

Intractable hypercalcaemia due to parathyroid hormone-related peptide secretion by a carcinoid tumour.

Hypercalcaemia, a common complication of malignancy, may result from either the lytic effect of multiple osseous metastases or the effect of tumour-derived humoral factors. Excessive secretion of parathyroid hormone-related peptide (PTHrP), a major cause of humoral hypercalcaemia of malignancy, has been incriminated as the cause of hypercalcaemia in patients with lung, breast, renal, head and neck and, occasionally, haematological malignancies. Carcinoid tumours, while frequently the source of ectopic hormone secretion, are infrequently associated with hypercalcaemia. We report the case of a 59-year-old woman with fulminant hypercalcaemia due to excessive PTHrP secretion from a hepatic carcinoid and we present the change in her serum PTHrP concentrations during infusion of a somatostatin analogue.

Antineoplastic Agents, Hormonal↗
PubMed1997

Leptin concentrations in relation to body mass index and the tumor necrosis factor-alpha system in humans.

The expression of leptin, an adipocyte-derived protein whose circulating levels reflect energy stores, can be induced by tumor necrosis factor (TNF)alpha in rodents, but an association between the TNF alpha system and leptin levels has not been reported in humans. To evaluate the potential association between serum leptin and the TNF alpha system, we measured the levels of soluble TNF alpha-receptor (sTNF alpha-R55), which has been validated as a sensitive indicator of activation of the TNF alpha system. We studied two groups: 1) 82 young healthy normal controls and 2) 48 patients with noninsulin dependent diabetes mellitus (NIDDM) and 24 appropriately matched controls. By simple regression analysis in controls, there was a strong positive association between leptin and 3 parameters: body mass index, sTNF alpha-R55, and insulin levels. In a multiple regression analysis model, leptin remained significantly and strongly associated with body mass index, and the association of leptin with both insulin and sTNF alpha-R55, although weakened, remained significant. Patients with NIDDM had leptin concentrations similar to controls of similar weight. Importantly, serum levels of sTNF alpha-R55 were also positively and independently associated with leptin in this group of diabetic subjects and matched controls. These data are consistent with the hypothesis that the TNF alpha system plays a role in regulating leptin levels in humans. Further elucidation of a possible role of the TNF alpha system in leptin expression and circulating levels may have important implications for our understanding of obesity and cachexia in humans.

Adolescent↗
PubMed1997

Short-term hyperthyroidism has no effect on leptin levels in man.

Leptin, a 16-kDa adipocyte-derived protein whose circulating levels reflect energy stores, increases the resting metabolic rate and thermogenesis in rodents. Thyroid hormones also increase the basal metabolic rate, but nothing is known about possible interactions between leptin and thyroid hormone. Activation of beta-adrenergic receptors decreases leptin levels in rodents. To test the hypothesis that thyroid hormones, by causing a "functional hyperadrenergic" state, result in decreased leptin concentrations in humans, we studied 22 normal healthy men before and after the administration of T3 for 1 week to induce moderate hyperthyroidism. Short term thyroid hormone excess does not alter circulating leptin concentrations despite a demonstrated effect on heart rate, systolic blood pressure, cholesterol levels, and metabolic indexes of bone turnover. Elucidation of the apparently separate pathways by which thyroid hormones, beta-agonists, and leptin regulate energy expenditure and food intake may have important implications for our understanding of the mechanisms for regulating energy homeostasis in health and disease.

Adolescent↗
PubMed1997

A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. V. Rising leptin levels may signal the onset of puberty.

Leptin, the product of the ob gene, is an adipocyte-derived hormone that signals the amount of adipose tissue energy stores to the brain and exerts major effects on energy homeostasis and neuroendocrine function. Leptin has recently been shown to affect reproductive function in leptin-deficient and normal rodents. As puberty, the process of sexual maturation and acquisition of reproductive competence, has been proposed to be triggered by the attainment of a critical amount and/or distribution of fat, we examined whether changes in circulating leptin levels could represent the hormonal signal responsible for triggering the onset of puberty in humans. Eight prepubertal boys (Tanner genital stage 1 or early stage 2 at the initiation of the study) were evaluated longitudinally for 2.5-5.1 yr depending on when Tanner stage 5 of genital development was achieved. Sera for the determination of leptin, testosterone, and dehydroepiandrosterone sulfate were obtained every 4 months during the period of the study. Compared to baseline prepubertal levels (8 months before the onset of puberty, as defined by the initial rise in testosterone above the detection limit of the assay), leptin levels rose by approximately 50% just before the onset of puberty and decreased to approximately baseline values after the initiation of puberty (P < 0.01, by ANOVA), remaining stable for more than 2 yr. These changes occurred despite constantly increasing body mass index (P < 0.05, by ANOVA). No significant association between leptin and dehydroepiandrosterone sulfate concentrations was detected. In conclusion, the levels of circulating leptin are consistent with the hypothesis that this molecule is an important signal responsible for triggering the onset of puberty. The stimulus for a surge in leptin levels just before the onset of puberty is currently unknown.

Body Mass Index↗
PubMed1997

Leptin concentrations in the polycystic ovary syndrome.

The polycystic ovary syndrome (PCOS) is characterized by menstrual disturbances, chronic anovulation and hyperandrogenism and is associated with insulin resistance and hyperinsulinemia. Leptin, the product of the ob gene, is an adipocyte-secreted molecule that signals the magnitude of energy stores to the brain and has been recently shown to have important effects on the reproductive axis of rodents. To assess the potential contribution of leptin to the pathogenesis of PCOS, we measured leptin levels in 24 obese women with PCOS and 12 weight- and age-matched controls and determined whether alterations in hyperinsulinemia produced by administration of the insulin-sensitizing agent troglitazone had an effect on serum leptin levels. Leptin concentrations at baseline were not different in women with PCOS (38.1 +/- 2.15 ng/mL) and controls (33.12 +/- 2.39 ng/mL). Moreover, leptin concentrations remained unchanged after treatment with troglitazone (38.1 +/- 2.15 vs. 39.21 +/- 2.65 ng/mL). Baseline leptin correlated strongly with body mass index in both controls (r = 0.59; P < 0.05) and women with PCOS (r = 0.70; P = 0.0004). Leptin levels were not associated with baseline insulin, testosterone, non-sex hormone-binding globulin (SHBG)-bound testosterone, dehydroepiandrosterone sulfate, estradiol, or SHBG. Finally, despite significantly reduced insulin, non-SHBG-bound testosterone, and estradiol levels after troglitazone treatment of women with PCOS, their leptin levels remained unchanged. We conclude that circulating leptin levels in patients with PCOS do not differ from those in age- and weight-matched controls. Furthermore, increased circulating insulin due to insulin resistance does not appear to alter circulating leptin levels in women with PCOS.

Adult↗
PubMed1997

Effect of birth weight and maternal smoking on cord blood leptin concentrations of full-term and preterm newborns.

Prematurity, maternal smoking, and low birth weight each result in neuroendocrine dysfunction and increased perinatal morbidity and mortality. Leptin, an adipocyte-secreted protein, has provided the first physiological link to the regulatory system controlling starvation-induced neuroendocrine changes in rodents. This study investigated whether leptin concentrations were detectable in cord blood of newborns, and assessed the effect of birth weight, prematurity, and maternal smoking on cord blood leptin concentrations. Fifty consecutively enrolled full-term and 12 preterm newborns born to mothers who smoked during pregnancy were compared to 50 full-term and 12 preterm newborns born to parents who were nonsmokers. RIA for leptin was performed using cord blood samples collected immediately after birth. Leptin concentrations were detectable in newborns and correlated positively with obesity (full-term, r = 0.30, P < 0.01; preterm, r = 0.47, P < 0.05). Maternal smoking during pregnancy was associated with decreased leptin concentrations in the cord blood of both full-term and preterm newborns. This effect was independent of obesity (full-term newborns: 5.25 +/- 2.48 vs. 4.21 +/- 2.71 ng/ml, P = 0.01) and was more pronounced in premature newborns (5.67 +/- 3.6 vs. 2.46 +/- 2.03, P = 0.02), and its magnitude in full-term newborns was directly related to the reported number of cigarettes the mothers of the full-term newborns smoked per day (r = -0.438, P < 0.001). Thus, low birth weight and maternal smoking are both associated with decreased leptin concentrations, and these effects are more pronounced in premature newborns. Future studies will be needed to determine whether administration of leptin might reverse the neuroendocrine dysfunction caused by maternal smoking.

Birth Weight↗