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R Rosmond

Publications and source records attributed to R Rosmond.

At least 37 records · Page 2Linked to original sources

G-308A polymorphism of the tumor necrosis factor alpha gene promoter and salivary cortisol secretion.

The objective of the current study was to examine the potential impact of the G-->A substitution at position -308 of the tumor necrosis factor alpha (TNF-alpha) gene promoter on obesity and estimates of insulin, glucose, and lipid metabolism as well as circulating hormones including salivary cortisol in 284 unrelated Swedish men born in 1944. The subjects were genotyped by using PCR amplification of the 5' untranslated region of the TNF-alpha gene followed by digestion with the restriction enzyme NcoI. The frequencies were 0.77 for allele G and 0.23 for allele A. Tests for differences in salivary cortisol levels between the TNF-alpha genotypes revealed that there were significantly higher cortisol levels in the morning, before as well as 30 and 60 min after stimulation by a standardized lunch in homozygotes for the rare allele in comparison with the other genotypes. In addition, homozygotes for the rare allele had a tendency toward higher mean values of body mass index, waist to hip ratio, and abdominal sagittal diameter compared with the other genotype groups. The results also indicated a weak trend toward elevated insulin and glucose levels among men with the A/A genotype. In conclusion, a G-->A polymorphism in the 5' untranslated region of the TNF-alpha gene is associated with elevated morning cortisol levels as well as elevated postprandial cortisol secretion. This increase in cortisol secretion might be the endocrine mechanism underlying the previously observed associations between the NcoI TNF-alpha polymorphism and obesity as well as insulin resistance. However, to what extent this polymorphism is associated with these conditions is uncertain from the present data.

Alleles↗

Polymorphisms of the androgen receptor gene and the estrogen receptor beta gene are associated with androgen levels in women.

To elucidate the possible role of genetic variation in androgen receptor (AR), estrogen receptor alpha (ER alpha), and ER beta on serum androgen levels in premenopausal women, the CAG repeat polymorphism of the AR gene, the TA repeat polymorphism of the ER alpha gene, and the CA repeat polymorphism of the ER beta gene were studied in a population-based cohort of 270 women. Total testosterone, free testosterone, dehydroepiandrosterone sulfate, androstenedione, 17-hydroxyprogesterone, 3 alpha-androstanediol glucuronide, 17 beta-estradiol, LH, FSH, and sex steroid hormone-binding globulin (SHBG) were measured in serum samples obtained in the follicular phase of the menstrual cycle. Women with relatively few CAG repeats in the AR gene, resulting in higher transcriptional activity of the receptor, displayed higher levels of serum androgens, but lower levels of LH, than women with longer CAG repeat sequences. The CA repeat of the ER beta gene also was associated with androgen and SHBG levels; women with relatively short repeat regions hence displayed higher hormone levels and lower SHBG levels than those with many CA repeats. In contrast, the TA repeat of the ER alpha gene was not associated with the levels of any of the hormones measured. Our results suggest that the serum levels of androgens in premenopausal women may be influenced by variants of the AR gene and the ER beta gene, respectively.

Adult↗

[Low cortisol production in chronic stress. The connection stress-somatic disease is a challenge for future research].

There is a general assumption that distressing events or situations (stress) evoke the hypothalamic-pituitary-adrenal (HPA) system, with a resulting increase in cortisol secretion. However, our increasing understanding of the complexity of the HPA axis physiology raises questions as to the validity of this model. An increasing number of studies imply that after long-term exposure to stress, the HPA axis will eventually become dishabituated, resulting in a disruption of central regulatory systems and a net decrease of cortisol output. These findings have major implications for the interpretation of stress-induced neuroendocrine response patterns.

Acute Disease↗

Obesity and cortisol.

Cortisol in obesity is a much-studied problem. Previous information indicates that cortisol secretion is elevated but that circulatory concentrations are normal or low, suggesting that peripheral disappearance rate is elevated. These studies have usually not taken into account the difference between central and peripheral types of obesity. Recent studies using saliva cortisol have indicated that the problem is complex with both high and low secretion of cortisol, perhaps depending on the status of the function of the hypothalamic-pituitary-adrenal gland axis. A significant background factor seems to be environmental stress. The results also suggest that the pattern of cortisol secretion may be important. Other neuroendocrine pathways are also involved, including the central sympathetic nervous system, the gonadal and growth hormone axes, and the leptin system. In concert, these abnormalities seem to be responsible for the abnormal metabolism often seen in central obesity. Several associated polymorphisms of candidate genes may provide a genetic background. Cortisol conversion to inactive metabolites may be a factor increasing central signals to secretion and may add to the increased secretion of cortisol induced by centrally acting factors. Perinatal factors have been found to be involved in the pathogenesis of obesity and its complications. The mechanism involved is not known, but available information suggests that programming of the hypothalamic-pituitary-adrenal axis may be responsible.

Animals↗

The metabolic syndrome--a neuroendocrine disorder?

Central obesity is a powerful predictor for disease. By utilizing salivary cortisol measurements throughout the day, it has now been possible to show on a population basis that perceived stress-related cortisol secretion frequently is elevated in this condition. This is followed by insulin resistance, central accumulation of body fat, dyslipidaemia and hypertension (the metabolic syndrome). Socio-economic and psychosocial handicaps are probably central inducers of hyperactivity of the hypothalamic-pituitary adrenal (HPA) axis. Alcohol, smoking and traits of psychiatric disease are also involved. In a minor part of the population a dysregulated, depressed function of the HPA axis is present, associated with low secretion of sex steroid and growth hormones, and increased activity of the sympathetic nervous system. This condition is followed by consistent abnormalities indicating the metabolic syndrome. Such 'burned-out' function of the HPA axis has previously been seen in subjects exposed to environmental stress of long duration. The feedback control of the HPA axis by central glucocorticoid receptors (GR) seems inefficient, associated with a polymorphism in the 5' end of the GR gene locus. Homozygotes constitute about 14% of Swedish men (women to be examined). Such men have a poorly controlled cortisol secretion, abdominal obesity, insulin resistance and hypertension. Furthermore, polymorphisms have been identified in the regulatory domain of the GR gene that are associated with elevated cortisol secretion; polymorphisms in dopamine and leptin receptor genes are associated with sympathetic nervous system activity, with elevated and low blood pressure, respectively. These results suggest a complex neuroendocrine background to the metabolic syndrome, where the kinetics of the regulation of the HPA axis play a central role.

Animals↗

A glucocorticoid receptor gene marker is associated with abdominal obesity, leptin, and dysregulation of the hypothalamic-pituitary-adrenal axis.

OBJECTIVE: Abdominal obesity has a key role in the pathogenesis of prevalent and serious diseases and has been shown to be associated with an altered hypothalamic-pituitary-adrenal (HPA) axis function, which is regulated by endocrine feedback mediated via hippocampal glucocorticoid receptors (GR). RESEARCH METHODS AND PROCEDURES: We examined the HPA axis function by repeated salivary samples for the assessment of cortisol, as well as other endocrine, anthropometric, metabolic, and circulatory variables in middle-aged Swedish men (n = 284). With the restriction enzyme BclI, variants of the GR gene (GRL) locus were identified and two alleles with fragment lengths of 4.5 and 2.3 kilobases (kb) were detected. RESULTS: The observed frequencies were 40.1% for the 2.3- and 2.3-kb, 46.2% for the 4.5- and 2.3-kb, and 13.7% for the 4.5- and 4.5-kb genotypes. The larger allele (4.5 and 4.5 kb) was associated with elevated body mass index (BMI; p < 0.001), waist-to-hip circumference ratio (p = 0.015), abdominal sagittal diameter (p = 0.002), leptin (p < 0.001), and systolic blood pressure (borderline, p = 0.058). The 4.5- and 4.5-kb allele was associated with leptin after adjustment for BMI. Moreover, salivary cortisol values, particularly after stimulation by a standardized lunch (p = 0.040 to 0.086), were elevated in the men with the larger allele. DISCUSSION: These results indicate that there is an association between a deficient GR function, defined as a poor feedback regulation of the HPA axis activity, and a polymorphic restriction site at the GR gene locus. An abnormal control of HPA axis function due to genetic alterations may contribute to the pathogenesis of abdominal obesity.

Adipose Tissue↗

Occupational status, cortisol secretory pattern, and visceral obesity in middle-aged men.

OBJECTIVE: Despite several studies indicating that social gradients are predictive of cardiovascular mortality, the pathogenetic mechanisms remain incompletely understood. RESEARCH METHODS AND PROCEDURES: A population sample of 51-year-old men (N = 284) was divided into a socioeconomic gradient with manual laborers, civil servants, and university graduates. Anthropometric measurements were registered. Cortisol concentrations were measured in saliva, collected repeatedly during an ordinary working day, and a low-dose dexamethasone suppression test was performed. RESULTS: Lower socioeconomic status was associated with visceral obesity and higher cortisol values in relation to perceived stress. However, total cortisol secretion over the day of study was not elevated. The regulation of cortisol secretion showed less plasticity and dexamethasone inhibition was less efficient in the men in the lower socioeconomic status group than in those with a higher socioeconomic status. These are known consequences of long term stress. Longer duration in low socioeconomic conditions seemed to worsen these phenomena. DISCUSSION: It was concluded that a low socioeconomic status is associated with perturbed cortisol secretion, which is elevated in relation to perceived stress. When the hypothalamic-pituitary-adrenal axis is subjected to prolonged increases in cortisol elicited by chronic stress, the regulation of cortisol secretion is affected, indicating neuroendocrine dysregulations. These observations may provide a means for understanding the association of socioeconomic impairments with visceral obesity and the social inequality in risk for prevalent and serious diseases.

Anthropometry↗

Food-induced cortisol secretion in relation to anthropometric, metabolic and haemodynamic variables in men.

OBJECTIVE: To assess the relationships between the regulation of diurnal and food-induced cortisol secretion and anthropometric, metabolic and haemodynamic variables in middle-aged men. SUBJECTS AND METHOD: Salivary cortisols were collected repeatedly (n = 7) over an ordinary working day (8a.m. to 11 p.m.) in a randomly selected population of 284 men, aged 51 y. A standardized lunch was provided, and an overnight low-dose dexamethasone suppression test was performed. These measurements were correlate with the anthropometric factors-body mass index, BMI, (kg/m2), waist-to-hip ratio (WHR) and abdominal sagittal diameter; the metabolic factors-fasting insulin and glucose as well as their ratio, and triglycerides; and the haemodynamic factors-systolic and diastolic blood pressures and heart rate. RESULTS: As reported previously two principal types of salivary cortisol secretory patterns can be singled out, one characterized by high morning cortisol levels, a normal circadian rhythm and feedback regulation (dexamethasone) along with a brisk cortisol response to lunch, and another, found in a limited number of men, characterized by low morning cortisols, the absence of a circadian rhythm, a relative resistance to dexamethasone inhibition and a poor lunch-induced cortisol response. The normal cortisol secretory pattern showed negative associations with BMI (P< 0.05), WHR (P< 0.01), and blood pressures (P< 0.001). After stimulation by food intake, negative relationships were found with all obesity measurements, insulin, insulin/glucose ratio, triglycerides, blood pressures and heart rate (all P < 0.001). These results suggest that normally regulated cortisol is associated with a favourable somatic health. In contrast, after food intake cortisol secretion, based on an abnormal cortisol secretory pattern, showed consistent positive associations with obesity measurements, insulin, glucose and insulin/glucose ratio, triglycerides, blood pressures and heart rate (all P < 0.001). CONCLUSIONS: A normal HPA axis regulation is associated with excellent health anthropometric, metabolic and haemodynamic variables, particularly visible after the physiological stimulus of food intake. This is, however, not the case in men with perturbed HPA axis function where associations in these somatic variables become exaggerated by food intake. We have previously reported that perceived stress-related cortisol is associated with abnormalities in the variables mentioned above, both with a normal and, particularly, with an abnormal function of the HPA axis. It is thus apparent that perceived stress and food intake show separate associations to somatic variables with a normally functioning HPA axis, while with an abnormal regulation of this axis both perceived stress and food intake exaggerate associations to abnormal somatic variables.

Abdomen↗

Neuroendocrine abnormalities in visceral obesity.

Central obesity is the subfraction which carries most of the risks for comorbidities. In this overview we suggest that this is due to neuroendocrine perturbations, where the hypothalamic-pituitary-adrenal (HPA) axis assumes a central role. The HPA axis is stimulated by central factors, which are often called stress. This is followed by discrete, periodical elevations of cortisol secretion during every day conditions. Such observations require diurnal measurements under undisturbed conditions. Saliva cortisol is useful for such purposes. It seems likely, based on cross-sectional observations in men and longitudinal studies in animals that a prolonged period of HPA axis stimulation is followed by a continuous degradation of the regulatory mechanisms. An end stage is a rigid cortisol secretion with low morning values. In parallel with this is a diminished function of the feed-back control as well as an inhibition of growth and sex steroid hormones. Evidence also suggests that the sympathetic nervous centers become activated in parallel. The net effects of this cascade of neuroendocrine-endocrine pertubations will be insulin resistance as well as visceral accumulation of body fat. These are effects of cortisol in combination with the diminished secretion of growth and sex steroid secretions, which in normal concentrations antagonize the cortisol effects. Blood pressure will also be elevated, which might be a consequence of central stimulation of the sympathetic nervous system, with added effects of insulin. What has developed is a hypothalamic arousal with the Metabolic Syndrome as a consequence. The feed-back regulation of the HPA axis has a key position in this chain of events. This control is mediated via glucocorticoid receptors in the lower parts of the brain. The gene for this receptor has shown polymorphisms which are associated with poorly regulated cortisol secretion, central obesity, insulin resistance and hypertension.

Adrenal Glands↗

Psychiatric ill health and distribution of body fat mass among female immigrants in Sweden.

Given the association between psychiatric factors and obesity, the aims of the present study were to identify these variables among native Swedish as well as immigrant women, and to compare the prevalence of psychiatric ill health in women of foreign ethnicity with Swedish women. Information on melancholia, life satisfaction, sleeping problems, and use of psychoactive drugs as well as alcohol and smoking habits was obtained from questionnaires in a randomly selected population (n = 1464, participation rate 78%, aged 40 y). Height, body weight and circumferences of waist and hip were self-measured, so allowing calculations of the body mass index (BMI) and the waist to hip ratio (WHR) to be made. Among those who responded 246 (21.9%) were immigrants, divided into the following demographic clusters Nordic countries; Rest of Europe; and Non-European. Among native Swedes, use of psychoactive drugs and melancholy were associated with both BMI and WHR. BMI-associated with use of antidepressants in women from Nordic countries with a short duration of stay, and in subjects with a long duration of residence, was related to life satisfaction. Among subjects from the Rest of Europe, the use of hypnotics was negatively related to BMI, and life satisfaction was positively associated with WHR. Among Non-Europeans with a long duration of residence, BMI was positively connected to the use of anxiolytics and, negatively, to life satisfaction. Furthermore, melancholy was positively associated with WHR (borderline, P=0.086) in Non-Europeans. Subjects from Nordic countries were characterised by a relatively low use of psychoactive drugs and infrequent insomnia. In contrast, subjects from the Rest of Europe with short duration of stay showed a relatively extensive use of psychoactive drugs, and the Non-European group with short duration of stay experienced frequent insomnia, and a low degree of life satisfaction as well as high degree of melancholy. The association between psychiatric factors and obesity is not uniform across ethnic groups, suggesting a combination of genetic predisposition and psychosocial vulnerability. The high prevalence of psychiatric ill health among some ethnic groups should be a matter of public health concern.

Adipose Tissue↗

The hypothalamic-pituitary-adrenal axis activity as a predictor of cardiovascular disease, type 2 diabetes and stroke.

OBJECTIVES: The hypothalamic-pituitary-adrenal (HPA) axis, the mediator of cortisol, plays a central role in the homeostatic processes. In this study, we addressed the potential impact of HPA axis activity on established anthropometric, metabolic and haemodynamic risk factors for cardiovascular disease (CVD), type 2 diabetes mellitus and stroke. DESIGN: A cross-sectional study. SUBJECTS: A subgroup of 284 men from a population sample of 1040 at the age of 51 years. MAIN OUTCOME MEASURES: Anthropometric measurements included body mass index (BMI, kg m-2), waist/hip circumference ratio (WHR) and abdominal sagittal diameter (D). Overnight fasting values of blood glucose, serum insulin, triglycerides, total, low (LDL) and high density (HDL) lipoprotein cholesterol, as well as resting heart rate and blood pressure, were also determined. By using repeated diurnal salivary cortisol measurements during everyday conditions, methods were developed to characterize the status of the HPA axis, and set in relation to the anthropometric, metabolic and haemodynamic measurements. RESULTS: In bivariate analyses, risk factors intercorrelated in clusters of anthropometric (BMI, WHR, D), metabolic (insulin, glucose and their ratio, triglycerides, cholesterol [total and LDL], HDL cholesterol [negative]) and haemodynamic (systolic and diastolic blood pressure and heart rate) measurements. This was also the case in the two-dimensional scaling analysis, where, however, HDL separated out. A normal HPA axis status, characterized by high variability and morning cortisol values, as well as a clear response to a standardized lunch and dexamethasone suppression test, was then introduced by a statistical weighting procedure. This did not essentially change the results of either the bivariate correlation matrix or the two-dimensional scaling analysis. A similar introduction of a pathological HPA axis, characterized by low variability and morning cortisol values, a poor lunch-induced cortisol response and a blunted dexamethasone suppression of cortisol, changed the results markedly. Now strong and consistent correlations were found not only within but also between different clusters of risk factors, which also congregated into one distinct cluster, again except for HDL cholesterol. CONCLUSIONS: These results disclose the prospect of an overriding function of a pathological HPA axis on other, established risk factors for CVD, type 2 diabetes and stroke. Its close association to HPA axis dysfunction may explain the previously reported powerful risk indication of abdominal obesity for the diseases mentioned. The HPA axis abnormality has been reported to be a characteristic consequence of frequently repeated or chronic environmental stress challenges.

Adipose Tissue↗

Polymorphisms of the beta2-adrenergic receptor gene (ADRB2) in relation to cardiovascular risk factors in men.

OBJECTIVE: To investigate the effect of polymorphisms in codon 16 (Arg16Gly) and codon 27 (Gln27Glu) of the beta2-adrenergic receptor gene (ADRB2) on anthropometric, endocrine, metabolic and haemodynamic variables. DESIGN: A cross-sectional study. SUBJECTS: A subgroup of 284 Swedish men from a population sample of 1040 at the age of 51 years. MAIN OUTCOME MEASURES: Genotype examination of ADRB2 polymorphisms in codon 16 and codon 27 with polymerase chain reaction and restriction fragment length polymorphism. Anthropometric measurements included body mass index, waist-to-hip ratio and abdominal sagittal diameter. Endocrine measurements included blood levels of testosterone, insulin-like growth factor I, and leptin plus salivary cortisol. Overnight fasting values of serum insulin, blood glucose, triglycerides, total, low and high density lipoprotein cholesterol, as well as blood pressure and resting heart rate, were also determined. RESULTS: Polymorphisms were frequent in both codon 16 and codon 27. The Arg16Gly genotype showed significant relationships to elevated central distribution of body fat and to systolic blood pressure, whilst the Glu27Glu genotype was associated with elevated leptin and triglyceride levels but not to other measurements, including obesity variables. CONCLUSIONS: We conclude that only a few cardiovascular risk factors are associated with DNA sequence variation in the ADRB2 in Swedish men.

Alleles↗

A polymorphism of the 5'-flanking region of the glucocorticoid receptor gene locus is associated with basal cortisol secretion in men.

There is growing evidence that cortisol secretion and/or metabolism is associated with cardiovascular risk factors. Previous studies have shown that cardiovascular risk factors are associated with stimulated cortisol secretion and not with basal cortisol secretion. With the restriction enzyme Tth111I, a variant of the 5'-flanking region of the glucocorticoid receptor gene locus (GRL) was identified. The genotypes were compared for measurements of cortisol secretion and cardiovascular risk factors in a cohort (N = 284) of randomly selected middle-aged men. The frequency of the 3.4/3.4-, 3.4/3.8-, and 3.8/3.8-kilobase (kb) genotypes was 49.6%, 41.4%, and 9.0% respectively. The 3.8-kb homozygotes showed higher total and evening cortisol levels with a trend for elevated levels over the day. Neither stimulated or suppressed cortisol secretion nor anthropometric, endocrine, metabolic, and hemodynamic cardiovascular risk factors were significantly different among the genotypes. Since the polymorphism studied herein is localized at the 5'-flanking region of the GRL, the results suggest that elevated basal cortisol secretion is associated with a polymorphism of the promoter region.

Alleles↗

The role of antidepressants in the treatment of abdominal obesity.

The pathophysiology of abdominal obesity is unclear and controversial. Recent evidence now suggests that inadequate cortisol secretion is associated with abnormalities in glucose, insulin and lipid metabolism, including hypertension, bringing the importance of the hypothalamic-pituitary-adrenal (HPA) axis in the pathogenesis of abdominal obesity to the forefront. In addition, abnormal gonadal steroid concentrations and impaired plasma growth hormone levels accompany the abdominally obese state. Since the reproductive and growth axes are inhibited at many levels by various components of the HPA axis, increasing cortisol levels results in further depression of testosterone and growth hormone concentrations. Over the last decade, antidepressant (serotoninergic) drugs have proved useful as equalizers of HPA axis hyperactivity. Such therapy may interrupt the vicious circle of a hyperactive HPA axis leading to increasing abdominal obesity and endocrine perturbations that, in turn, leads to progressive accumulation of abdominal fat. Additionally, preliminary results indicate that serotoninergic agents decrease abdominal fat mass with improvements in related risk factors.

Abdomen↗

Hypertension and the metabolic syndrome: closely related central origin?

In primary hypertension a mild hyperresponsiveness of hypothalamic, sympatho-hormonal centres to psychosocial stimuli forms a major pathogenetic element, although high salt intake in some subjects may contribute via volume expansion. Hypertension is often associated with another "civilisation" disorder, the metabolic syndrome, defined as abdominal obesity, insulin resistance and dyslipidaemia. According to recent research, the metabolic syndrome has in all likelihood a central neuroendocrine origin in the form of enhanced engagement of the hypothalamic-pituitary-adrenal (HPA) axis. Here the peripheral endocrine perturbations act as triggers for both central obesity and the metabolic abnormalities. The reaction pattern characterising early primary hypertension is identical with, or closely related to, the "defence reaction", while that leading to the metabolic syndrome is similar to that of the "defeat reaction". Both belong to the primitive survival reactions, common to all mammals, though man can control, or at least mask, his outward-behavioural part but not the neuro-hormonal expressions. Animal experiments show how frequent or chronic mental challenges are capable of engaging these limbic-hypothalamic centres, affecting blood pressure regulation as well as endocrine-metabolic regulation. Furthermore, these centres are tightly coupled functionally, and their signals to the periphery often combined. On a long-term basis their engagements appear to be decisive for the development of both primary hypertension and the metabolic syndrome, as suggested by intervention studies. In both these "disorders of civilisation", observations strongly indicate that psychosocial stress, socioeconomic handicaps, lack of exercise, abuse and also psychiatric traits are involved. Such factors, characteristic of current competitive society, probably cause mixed engagements of the two above-mentioned neuro-hormonal patterns, and thereby, with time, primary hypertension and the metabolic syndrome, with end-points such as coronary artery disease, diabetes mellitus type2 and stroke. Susceptibility to such developments is probably enhanced by genetic factors. This overview of recent developments therefore serves to emphasise how both primary hypertension and the metabolic syndrome seem to have a common central origin. Central regulatory factors are often overlooked, partly because it is not realised that limbic-hypothalamic centres are the major regulators of both circulatory and metabolic events, and partly because of the long period of time required before these disease end-points are reached.

Abdomen↗

Quality of life, overweight, and body fat distribution in middle-aged men.

Measurements of obesity [body mass index (BMI)] and body fat distribution [waist-to-hip ratio (WHR)] were analyzed in 284 51-year-old men in relation to items about social, mental, and physical well-being from the Göteborg Quality of Life Instrument. Overweight participants (BMI > or = 25) reported a better home-family situation, appetite, and self-esteem, but decreased physical fitness and more pain in the legs compared with their leaner counterparts. Men with abdominal obesity (WHR > or = 1.0) experienced impaired health and physical fitness and lower self-esteem compared with those with WHR < 1.0. The abdominally obese participants were more often exhausted and experienced depressive symptoms. Abdominal pain was more frequent among those with WHR > or = 1.0. Overweight and abdominal obesity seem differently associated with social, mental, and physical well-being in men. Impaired quality of life may be causally related to the development of abdominal obesity; the mechanism involved might be increased cortisol secretion, which can redistribute body fat to central adipose tissue depots.

Body Constitution↗

Gender-related behavior during childhood and associations with adult abdominal obesity: a nested case-control study in women.

Abdominal obesity affects many aspects of women's health, and recent studies indicate that hyperandrogenicity (HA) may contribute to the excess of body fat in women. As hormone behavior research attributes male-like play patterns in childhood to the effects of androgens, the aim of the present study was to assess the potential association of such behavior with obesity in adult women. In a randomly selected sample of 40-year-old women (n = 1464), 78% volunteered to respond to a questionnaire collecting information on the effect of other variables on childhood behavior. Self-reported body weight, height, and waist and hip circumferences were used to calculate body mass index (BMI) and waist/hip ratio (WHR). Age at menarche showed an inverse association with overweight (BMI > or = 25) (odds ratio [OR] = 0.82). Reports of gender-related behavior as a child showed that playing with girls and girl toys was negatively related to both overweight and abdominal obesity (WHR > or = 0.85). Among respondents who were overweight, relationships were found for playing with boys (OR = 0.90) and fighting (OR = 1.70). The OR of playing with boy toys and fighting among respondents with abdominal obesity were increased 1.12 and 1.65, respectively. Interests in athletics as a child seemed to decrease the risk for overweight (OR = 0.89) and abdominal obesity (OR = 0.91). Furthermore, dose-response analysis between the individual exposure levels and the OR for overweight showed a negative trend for playing with girls (p = 0.002) and girl toys (p = 0.017) and a positive trend for playing with boys (p = 0.011) and fighting (p = 0.031). Among respondents with abdominal obesity, positive dose-response effects were found for playing with boys (p = 0.026) and boy toys (p = 0.036) and fighting (p = 0.008). Thus, women with an elevated WHR showed a preference to play with boys and boy toys and also fought frequently as children. This might be a sign of a relative HA in childhood ("tomboyism"). These preliminary observations suggest that HA may originate in childhood.

Abdomen↗

Hypertension in obesity and the leptin receptor gene locus.

Recent animal studies indicate that leptin is involved in the regulation of blood pressure through the leptin receptor. Therefore, 51-yr-old men (N = 284) were selected; and anthropometric, endocrine, metabolic, and hemodynamic variables were examined in relation to polymorphisms of the leptin receptor gene (LEPR), by restriction fragment length polymorphism technique. Three polymorphisms were examined: Lys109Arg in exon 4, Gln223Arg in exon 6, and Lys656Asn in exon 14. In comparison with Lys109 homozygotes, Arg109 homozygotes (9%) showed lower body mass index (BMI) and abdominal sagittal diameter, as well as lower systolic (10.0 mm Hg) and diastolic (7.8 mm Hg) blood pressure. Additionally, Arg223 homozygotes (26.8%) showed lower blood pressure (7.6/5.7 mm Hg) than Gln223 homozygotes. These lower blood pressure levels were independent of other variables. No differences were found with the Lys656Asn polymorphism. Measurements of body fat mass correlated with leptin concentration in Lys109 homozygotes and in Lys109 heterozygotes but not in Arg109 homozygotes. Blood pressure correlated with leptin only in men carrying the wild-type allele Lys109. With both elevated BMI and leptin, Lys109 homozygotes had higher blood pressure than the Arg109 homozygous men (12.4/6.9 mm Hg). Men with blood pressure > or = 140/90 mm Hg had, in comparison with normotensive men, increased BMI and leptin levels, and Lys109 homozygotes were significantly more prevalent. These results suggest that leptin is associated with blood pressure regulation in men through the leptin receptor. When BMI and leptin are elevated, increased blood pressure is found only with the most prevalent LEPR genotype at codons 109 and 223, whereas variants of this receptor seem to protect from hypertension. This might explain why not all obese men are hypertensive.

Adult↗