Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the hypothesis that endocrine profiles change with aging independently of specific disease states, we examined the age trends of 17 major sex hormones, metabolites, and related serum proteins in 2 large groups of adult males drawn from the Massachusetts Male Aging Study, a population-based cross-sectional survey of men aged 39-70 yr conducted in 1986-89. Group 1 consisted of 415 men who were free of obesity, alcoholism, all prescription medication, prostate problems, and chronic illness (cancer, coronary heart disease, hypertension, diabetes, and ulcer). Group 2 consisted of 1294 men who reported 1 or more of the above conditions. Each age trend was satisfactorily described by a constant percent change per yr between ages 39-70 yr. Free testosterone declined by 1.2%/yr, and albumin-bound testosterone by 1.0%/yr. Sex hormone-binding globulin (SHBG), the major serum carrier of testosterone, increased by 1.2%/yr, with the net effect that total serum testosterone declined more slowly (0.4%/yr) than the free or albumin-bound pools alone. Among the major androgens and metabolites, androstane-3 alpha,17 beta-diol (androstanediol; 0.8%/yr) and androstanediol glucuronide (0.6%/yr) declined less rapidly than free testosterone, while 5 alpha-dihydrotestosterone remained essentially constant between ages 39-70 yr. Androstenedione declined at 1.3%/yr, a rate comparable to that of free testosterone, while the adrenal androgen dehydroepiandrosterone (3.1%/yr) and its sulfate (2.2%/yr) declined 2-3 times more rapidly. The levels of testosterone, SHBG, and several androgen metabolites followed a parallel course in groups 1 and 2, remaining consistently 10-15% lower in group 2 across the age range of the study. Subgroup analyses suggested that obese subjects might be responsible for much of the group difference in androgen level. Serum concentrations of estrogens and cortisol did not change significantly with age or differ between groups. Of the pituitary gonadotropins, FSH increased at 1.9%/yr, LH increased at 1.3%/yr, and PRL declined at 0.4%/yr, with no significant difference between groups 1 and 2.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. 171 16

To study the effect of obesity on the metabolism of adrenal androgens not bound to testosterone-estradiol-binding globulin, the MCRs of delta 4-androstenedione (A) and dehydroepiandrosterone (DHEA) were determined using constant infusion of unlabeled steroids to steady state in 8 normal weight and 19 obese nonhirsute eumenorrheic women. The blood production rates (PR) were calculated as the product of the MCR and the 24-h integrated serum concentrations (IC). The mean MCR and PR of A and DHEA were significantly higher in the obese women than in the normal weight women. There was, however, no difference in the mean IC of each androgen in the 2 groups. The MCR and PR of A and DHEA were each correlated with the body mass index (BMI; kilograms per m2). The MCR and PR of A and the MCR of DHEA were also correlated with the ratio of waist circumference to hip circumference (WHR). However, the PR of DHEA was not correlated with WHR. There was no correlation between the IC of either androgen and BMI or WHR. However, partial correlation analysis revealed that correction of the BMI for WHR resulted in a significant negative correlation between BMI and IC of A. We conclude that the MCR and PR of A and DHEA were increased in obese nonhirsute eumenorrheic women; there was a strong correlation between BMI and the MCR and PR of A and DHEA; upper segment obesity, as measured by WHR, was correlated with the MCR and PR of A and the MCR of DHEA, but not with the PR of DHEA; and circulating DHEA and A were maintained at normal levels in the obese eumenorrheic women despite an increase in the MCR, which suggests that a servo-mechanism is operative which registers the body size and adjusts the PR according to the MCR.
 ...
PMID:Maintenance of normal circulating levels of delta 4-androstenedione and dehydroepiandrosterone in simple obesity despite increased metabolic clearance rates: evidence for a servo-control mechanism. 295 65

A patient with Cushing's syndrome due to ectopic ACTH secretion was treated successfully with the new glucocorticoid antagonist RU 486 [17 beta-hydroxy-11 beta-(4-dimethylamino phenyl) 17 alpha-(1-propynyl)estra-4,9-dien-3-one]. This compound is a 19-nor steroid with substitutions at positions C11 and C17 which antagonizes cortisol action competitively at the receptor level. Oral RU 486 was given in increasing doses of 5, 10, 15, and 20 mg/kg . day for a 9-week period. Treatment efficacy was monitored by assessment of clinical status and by measuring several glucocorticoid-sensitive variables, including fasting blood sugar, blood sugar 120 min after oral glucose administration, and plasma concentrations of TSH, corticosteroid-binding globulin, LH, testosterone-estradiol-binding globulin, and total and free testosterone. With therapy, the somatic features of Cushing's syndrome (buffalo hump, central obesity, and moon facies) ameliorated, mean arterial blood pressure normalized, suicidal depression resolved, and libido returned. All biochemical glucocorticoid-sensitive parameters normalized. No side-effects of drug toxicity were observed. We conclude that RU 486 may provide a safe, well tolerated, and effective medical treatment for hypercortisolism.
 ...
PMID:Successful treatment of Cushing's syndrome with the glucocorticoid antagonist RU 486. 299 27

10 examine the relationship between obesity and chronic anovulation, we compared basal serum LH, FSH, and PRL levels, determined at 20-min intervals, and basal C21 [progesterone, 17- hydroxyprogesterone , pregnenolone, 17-hydroxypregnenolone ( 17Pe ), and cortisol], C19 [testosterone (T), delta 4-androstenedione (A), and dehydroepiandrosterone] and C18 (estrone and estradiol) steroid hormone concentrations measured at 1- to 2-h intervals for a 24-h period in five normal weight cycling women (NC) and in two groups of weight-matched obese women. Five of the obese women were regularly cycling (OC), and six were amenorrheic (OA). Sex hormone-binding globulin (SHBG) and non-SHBG-bound T and estradiol concentrations were also measured in each woman. Compared to NC women, OC women had normal basal protein and steroid hormone concentrations, except for reduced 17Pe levels (P less than 0.05). Mean SHBG concentrations were reduced by approximately 30%, and non-SHBG-bound T was increased by 70%, although the differences were not significant. In addition, when six precursors of testosterone (pregnenolone, 17Pe , dehydroepiandrosterone, progesterone, 17-hydroxyprogesterone, and A) were considered together as a group and the data analyzed by the kappa 2 test, a reduction in basal levels of these precursors was found in OC women relative to those in NC women (P less than 0.005). In OA women, mean concentrations of SHBG were markedly reduced and those of total T, A, estrone, and non-SHBG-bound T were significantly increased compared to those in both NC and OC women. Mean 24-h concentrations of LH tended to be greatest and FSH lowest in this group, but were not significantly different from those in the other groups. The mean LH pulse frequency was significantly greater in OA than in OC women (P less than 0.05). Mean 24-h PRL and cortisol levels were also reduced in OA women relative to those in NC women. These data suggest the possibility of a compensatory decline in total T production in OC women in an attempt to maintain normal hormonal homeostasis; as a consequence, ovulation continues in a cyclic fashion. In OA women, such compensatory mechanisms are no longer operative. Instead, a central and/or peripheral defect, resulting in overproduction of androgen, may also exist and lead to anovulation in OA women. In conclusion, our data imply that obesity is not a primary factor causing chronic anovulation. However, obesity may aggravate an already existing subtle defect in some women and result in amenorrhea.
 ...
PMID:Endocrine comparison of obese menstruating and amenorrheic women. 642 58

Serum testosterone-estradiol binding globulin levels (TEBG), total and free testosterone levels, were evaluated in 36 patients with polycystic ovarian syndrome (PCO), and nine volunteers with normal cycles. TEBG concentration was markedly reduced in all PCO patients in comparison to the controls. However, the difference between the means was statistically significant for the obese PCO patients only. The serum free testosterone levels were elevated in all PCO patients, although the total testosterone levels were normal in 42.8% of obese and 13.3% of nonobese patients. It is suggested that obesity is a factor in causing reduction of TEBG levels. Also, it might be a contributory factor in the etiology of PCO.
 ...
PMID:The relation between obesity and testosterone-estradiol binding globulin levels in polycystic ovarian syndrome (PCO). 719 60

Sex hormone-binding globulin (SHBG) is an important regulator of plasma sex steroids as well as a sensitive indicator of insulin resistance. SHBG may be an important diagnostic measure of risk for pathologies associated with insulin resistance syndrome (IRS) such as non-insulin-dependent diabetes mellitus (NIDDM), obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. In women, SHBG is also implicated in diverse pathologies such as cancers of steroid-sensitive tissues and hirsutism. Data from an ongoing ecological study linking diet and health in rural China were analyzed to determine the relation of selected plasma variables and diet to plasma concentrations of SHBG. All data represent county mean values, pooled by age and sex, to assess the relation between biochemical and lifestyle characteristics and disease-specific mortality rates at the county level. The study sample consisted of 3250 Chinese women between the ages of 35 and 64 y living in 65 widely dispersed rural counties. Consumption patterns for 21 different food groups were derived from a food-frequency questionnaire and a 3-d dietary survey and subsequently compared. Correlation analyses of county mean values demonstrated a significant association between SHBG and insulin, testosterone, triacylglycerols, body mass index, age at menarche, and several foods. In regression analyses, after adjustments, the strongest predictors of SHBG concentrations were the dietary intake of rice (beta = 0.42, P < 0.01), fish (beta = 0.34, P < 0.05), millet (beta = -0.27, P < 0.01), and wheat (beta = -0.34, P < 0.01). When insulin, testosterone, and triacylglycerols were added to the model only triacylglycerols (beta = -0.26, P < 0.05) remained a significant independent predictor of SHBG. Additional analyses suggested that the consumption of green vegetables was modestly positively correlated with SHBG and negatively with insulin values. Consumption of rice and fish in particular appeared to favorably influence the principle plasma variables associated with a reduction in the risk for IRS pathologies.
 ...
PMID:Association of dietary factors and selected plasma variables with sex hormone-binding globulin in rural Chinese women. 860 65

Sex hormone-binding globulin (SHBG) binds testosterone, determining the level of free, biologically active hormone, and is a sensitive indicator of androgen status in women. SHBG is strongly correlated with high-density lipoprotein (HDL), central obesity, and insulin sensitivity in Caucasian and Mexican-American women, thereby acting as a biologic marker for cardiovascular disease risk. The purpose of this study was to determine if SHBG was a significant correlate of metabolic cardiovascular risk factors in African-American women. Eighty-one nondiabetic, normotensive African-American women were enrolled (mean age, 30 years). After excluding women on oral contraceptives (n = 19), 62 women were examined during the follicular phase of the menstrual cycle. All subjects underwent an oral glucose tolerance test (OGTT) and a euglycemic-hyperinsulinemic insulin clamp, and the lipid and sex hormone levels were measured. Correlation analyses showed a significant correlation between SHBG and the following variables in women: central obesity, body mass index (BMI), HDL cholesterol, apolipoprotein B (apoB), insulin sensitivity adjusted for lean mass (M'), and the sum of insulin during the OGTT. The strongest correlates of SHBG in women were measures of insulin resistance (r = .421, P < .001). SHBG appears to be a biologic marker for insulin resistance, which is linked to cardiovascular risk, in African-American women.
 ...
PMID:Sex hormone-binding globulin and insulin resistance in African-American women. 944 Apr 80

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, chronic anovulation, and oligomenorrhea (O/M). PCOS has variable clinical phenotypes, biochemical features, and metabolic abnormalities. To determine the prevalence of PCOS in the Greek population as well as the metabolic parameters, we performed a cross-sectional study of 192 women of reproductive age (17-45 yr), living on the Greek island of Lesbos. They were divided into 4 groups according to the presence of hirsutism (defined as a Ferriman-Gallwey score > or = 6) and O/M: group N (n = 108), regular menses and absence of hirsutism; group 1 (n = 56), regular menses and hirsutism; group 2 (n = 10), O/M and absence of hirsutism; and group 3 (n = 18), O/M and hirsutism. Body mass index, waist to hip ratio, and mean blood pressure did not differ among the studied groups. Hormonal profile was assessed by measuring free testosterone (FT). The prevalence of PCOS, defined by the presence of O/M and biochemical hyperandrogenism (FT > or = 95th percentile of the normal women), was estimated to be 6.77% (13 women of 192). Higher FT levels were observed in group 3 (O/M and hirsutism) compared with groups N (P < 0.00001) and 1 (P < 0.0001) and in groups 1 (hirsutism) and 2 (O/M) compared with group N (P < 0.0001 and P < 0.005, respectively). Sex hormone-binding globulin levels were lower in women with PCOS and in groups 1 and 3 than those in group N (P < 0.002, P < 0.02, and P < 0.002, respectively) independently of the body mass index. The metabolic profile was investigated by measurements of fasting glucose (FG), fasting insulin (FI), and estimation of the fasting glucose to insulin ratio (FG:I ratio). After covariance adjusted for the BMI, FI levels were higher in group 3 and in women with PCOS than in the normal (P < 0.005 and P < 0.002, respectively) and the hirsute (P < 0.05 and P < 0.02, respectively) women, whereas FG levels did not differ among the studied groups. The FG:I ratio was lower in group 3, group 1, and in women with PCOS than in normal women (P < 0.05). Finally, a high incidence of family history of diabetes mellitus (P = 0.001) and menstrual disorders (P = 0.01) was observed in women with PCOS, in contrast to the normal and hirsute women. In conclusion, PCOS appears to be a particularly common endocrine disorder in the Greek population under study (prevalence, 6.77%); furthermore, it is associated with certain metabolic abnormalities. These data also suggest that the severity of the fasting hyperinsulinemia is associated with the severity of the clinical phenotype of hyperandrogenism independently of obesity.
 ...
PMID:A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. 1056 41

Sex hormone-binding globulin (SHBG) is a plasma glycoprotein with high binding affinity for testosterone and dihydrotestosterone and lower affinity for estradiol. SHBG is synthesized in the liver, and its plasma level is important in the regulation of plasma free and albumin-bound androgens and estrogens. Obesity and particularly excess visceral fat, known risk factors for cardiovascular and metabolic diseases, are associated with decreased testosterone levels in males and SHBG levels in both sexes. SHBG is usually positively correlated with high-density lipoprotein cholesterol and negatively correlated with triglyceride and insulin concentrations. A positive association between SHBG and various measures of insulin sensitivity has been demonstrated in both sexes, suggesting that decreased SHBG levels may be one of the components of the metabolic syndrome. We have examined pituitary-adrenocortical function, glucose tolerance, and lipoprotein and hormone levels in a large cohort of Finnish males. Abdominal obesity appears to be associated with slight hypocortisolemia and increased sensitivity to exogenous adrenocorticotropin stimulation, which may contribute to the hyperinsulinemia and related metabolic changes including decreased SHBG levels in males.
 ...
PMID:Synthesis and regulation of sex hormone-binding globulin in obesity. 1099 12

We used longitudinal data from the Massachusetts Male Aging Study, a large population-based random-sample cohort of men aged 40-70 yr at baseline, to establish normative age trends for serum level of T and related hormones in middle-aged men and to test whether general health status affected the age trends. Of 1,709 men enrolled in 1987-1989, 1,156 were followed up 7-10 yr afterward. By repeated-measures statistical analysis, we estimated simultaneously the cross-sectional age trend of each hormone between subjects within the baseline data, the cross-sectional trend between subjects within the follow-up data, and the longitudinal trend within subjects between baseline and follow-up. Total T declined cross-sectionally at 0.8%/yr of age within the follow-up data, whereas both free and albumin-bound T declined at about 2%/yr, all significantly more steeply than within the baseline data. Sex hormone-binding globulin increased cross-sectionally at 1.6%/yr in the follow-up data, similarly to baseline. The longitudinal decline within subjects between baseline and follow-up was considerably steeper than the cross-sectional trend within measurement times for total T (1.6%/yr) and bioavailable T (2-3%/yr). Dehydroepiandrosterone, dehydroepiandrosterone sulfate, cortisol, and estrone showed significant longitudinal declines, whereas dihydrotestosterone, pituitary gonadotropins, and PRL rose longitudinally. Apparent good health, defined as absence of chronic illness, prescription medication, obesity, or excessive drinking, added 10-15% to the level of several androgens and attenuated the cross-sectional trends in T and LH but did not otherwise affect longitudinal or cross-sectional trends. The paradoxical finding that longitudinal age trends were steeper than cross-sectional trends suggests that incident poor health may accelerate the age-related decline in androgen levels.
 ...
PMID:Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. 1183 90


1 2 Next >>