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

A method is presented for radioimmunological determination of 3alpha, 5beta-tetrahydroaldosterone. It is based upon the reactivity of this steroid with an antiserum induced by the 3-carboxymethyloxime of 18, 21-aldosterone diacetate conjugated with bovine serum albumin. One hundred microliters of urine enzymatically hydrolyzed with an helix pomatia preparation, containing tritiated tetrahydroaldosterone for the yield calculation, were extracted with dichloromethane and chromatographed on a small celite column. The yield after extraction and chromatography was 64 +/- 17%. The radioimmunological determination was carried out in a conventional manner. The method is specific, sensitive (10 pg/tube), exact, reproducible, very simple and extremely rapid. The results showed good agreement with values given by a colorimetric method (p less than 0.001). The median value measured in 45 healthy adult subjects under standard sodium diet was 53.3 microgram/24h (95 % of the population within a 16.6 to 131.1 microgram/24h range). In 78 cases of adrenocortical insufficiency, 60 cases of obesity and 28 cases of hypokalemia, the median values (and the ranges : microgram/24h) were respectively 7.7 (1.0 - 51.0), 80.9 (17.0 - 503.0) and 64.3 (8.0 - 181.0). In 330 hypertensive patients the excretion of tetrahydroaldosterone exceeded the normal range in 115 cases (35%) with a median of 199.7 microgram/24h (131 to 620 microgram/24h).
Steroids 1977 Jun
PMID:Radioimmunological determination of urinary tetrahydroaldosterone. 91 Feb 48

To determine the sensitivity of the overnight 1-mg dexamethasone suppression test in diagnosing Cushing's syndrome, we evaluated the cortisol responses of 55 subjects (25 non-obese individuals with body mass index less than 25 kg/m2, 20 obese individuals with body mass index greater than 30 kg/m2, and 10 patients with surgically proven Cushing's syndrome) following ingestion of 1 mg dexamethasone at midnight. The basal 8 AM plasma cortisol levels among non-obese and obese individuals and patients with Cushing's syndrome were 310 +/- 85, 377 +/- 91, and 813 +/- 270 nmol/L, respectively. Following 1 mg of dexamethasone, Cushing's syndrome patients showed minimal suppression of cortisol to 609 +/- 180 nmol/L (P = 0.79). Non-obese and obese individuals suppressed to 18.7 +/- 6.0 nmol/L (P less than 0.001) and 22 +/- 7.1 nmol/L (P = 0.003), respectively. The results demonstrated similar cortisol responses to overnight dexamethasone suppression in obese and non-obese groups, and clearly distinguished these subjects from those with Cushing's syndrome. Obesity is not a confounding factor in the 1-mg dexamethasone suppression test.
Steroids 1991 Nov
PMID:Overnight (1 mg) dexamethasone suppression testing reliably distinguishes non-cushingoid obesity from Cushing's syndrome. 181 20

A male to female ration of coronary disease of 2:1 has been a consistent finding. This differential persists event when the classic risk factors for coronary disease--hypertension, smoking, obesity, diabetes, and hyperlipidemia--are controlled for gender. The most likely ultimate cause of this phenomenon is male-female differences in sex hormone patterns. Clinical studies in this area have either compared the sex hormone profiles of men and women with and without coronary disease or computed the relative prevalence of disease in populations that differ in their sex hormone patterns. In general, research findings have disputed the hypothesis that persons with coronary disease have low levels of a protective factor such as estrogen or progesterone and high levels of testosterone. Coronary disease patients actually have elevated estrogen levels and low testosterone levels; endogenous progesterone levels are normal before infarction but show a stress-mediated increase in the immediate postinfarction period. Findings of a low prevalence of coronary disease in premenopausal women, a loss of protection after menopause, and a low prevalence of coronary disease in men with cirrhosis-related hyperestrogenemia suggest that natural estrogens are antiatherogenic. The protective effect of pregnancy against myocardial infarction, despite concomitant potentially thrombogenic levels of estrogen at the time, seems to indicate that progesterone, whose levels are also extremely high during pregnancy, plays a major anti-infarction protective effect distinct from that of estrogen. Studies of women oral contraceptive (OC) users and men taking estrogens for brief periods have found that these exogenous hormones produce coronary thrombosis but not atherosclerosis. Finally, the finding of increased coronary disease risk in long-term OC users indicates that synthetic estrogens favor coronary atherosclerosis by suppressing natural estrogen and progesterone production.
Steroids 1990 Aug
PMID:Sex hormones and coronary disease: a review of the clinical studies. 223 42

This review examines the relationship between renal transplantation and two important metabolic consequences: hyperlipidemia and glucose intolerance. Before cyclosporine, hypertriglyceridemia and hypercholesterolemia were common abnormalities that worsened in the cyclosporine era. In addition to obesity, steroid use, and reduced renal function, cyclosporine plays an independent role in elevating cholesterol levels, with particular reference to the modulation of the low-density lipoprotein receptor. Management includes maintaining low levels of steroid, manipulation of cyclosporine appropriately, diets low in fat and cholesterol, and an exercise program. Pharmacologic management in general revolves around the HMG-COA reductase drugs, which can be used safely if liver function tests and muscle enzymes are monitored. The unmasking of clinically important glucose intolerance occurs in 5 to 10% of patients in the cyclosporine era, not different from the earlier experience. Steroids and cyclosporine independently can worsen glucose tolerance to unmask a genetic predisposition to Type II diabetes in some and to even create glucose intolerance in otherwise normal individuals. Management is based on dietary and immunosuppressive drug dosing manipulations and the judicious use of oral hypoglycemic agents. Half of these recipients may ultimately need insulin. In summary, hyperlipidemia and glucose intolerance remain important metabolic consequences of renal transplantation that affect long-term patient survival unless recognized and treated.
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PMID:Hyperlipidemia and glucose intolerance in the post-renal transplant patient. 819 94

Human and some other primates are unique since their adrenals secrete large amounts of dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), which are converted into androstenedione (4-dione) and then into potent androgens and estrogens in peripheral tissues, therefore providing autonomous intracrine control to target tissues that can adjust the formation and metabolism of active sex steroids according to local requirements. Knowledge in this area has recently made rapid progress with the elucidation of the structure of most of the tissue-specific cDNAs and genes that encode the steroidogenic enzymes responsible for the transformation of these inactive precursor steroids into androgens and/or estrogens. It is estimated that 30 to 50% of total androgens in men are synthesized in peripheral intracrine tissues from inactive adrenal precursors while, in women, peripheral estrogen formation is even more important, the best estimate being 75% before menopause and 100% after menopause. The marked reduction in the formation of DHEA-S by the adrenals during aging, especially before the age of 50 years, results in a dramatic fall in the formation of active sex steroids in peripheral target tissues, a situation which is thought to be associated with a long series of age-related decreases such as insulin resistance, obesity, osteoporosis, cardiovascular diseases, loss of muscle mass, cancer and other diseases. We have demonstrated for the first time a series of medically important beneficial effects of DHEA administered for 12 months to post-menopausal women. Most interestingly, the bone mineral density significantly increased. This relatively rapid change was associated with an increase in plasma osteocalcin, a marker of bone formation, while a decrease in bone resorption reflected by a decrease in urinary hydroxyproline excretion was observed in parallel. In addition, the estrogenic stimulation of vaginal cytology in the absence of any sign of stimulatory effect on the endometrium is also of potentially major interest for the prevention and management of menopause. Furthermore, the inhibitory effect of DHEA on the growth of human breast cancer xenografts in vivo in nude mice supports the beneficial use of DHEA as hormone replacement therapy in women.
Steroids
PMID:DHEA and the intracrine formation of androgens and estrogens in peripheral target tissues: its role during aging. 961 95

The role of glucocorticoids in obesity is poorly understood. Observations in obese men suggest enhanced inactivation of cortisol by 5alpha-reductase and altered reactivation of cortisone to cortisol by 11betahydroxysteroid dehydrogenase type 1 (11betaHSD1). These changes in glucocorticoid metabolism may influence corticosteroid receptor activation and feedback regulation of the hypothalamic-pituitary-adrenal axis (HPA). We have compared corticosterone metabolism in vivo and in vitro in male obese and lean Zucker rats, aged 9 weeks (n = 8/group). Steroids were measured in 72-h urine and 0900 h trunk blood samples. 5alpha-Reductase type 1 and 11betaHSD activities were assessed in dissected tissues. Obese animals were hypercorticosteronemic and excreted more total corticosterone metabolites (2264+/-623 vs. 388+/-144 ng/72 h; P = 0.003), with a greater proportion being 5alpha-reduced or 11-oxidized. 11-Dehydrocorticosterone was also elevated in plasma (73+/-9 vs. 18+/-2 nM; P = 0.001) and urine (408+/-111 vs. <28 ng/72 h; P = 0.01). In liver of obese rats, 5alpha-reductase type 1 activity was greater (20.6+/-2.7% vs. 14.1+/-1.5%; P<0.04), but 11betaHSD1 activity (maximum velocity, 3.43+/-0.56 vs. 6.57+/-1.13 nmol/min/mg protein; P = 0.01) and messenger RNA levels (0.56+/-0.08 vs. 1.03+/-0.15; P = 0.02) were lower. In contrast, in obese rats, 11betaHSD1 activity was not different in skeletal muscle and sc fat and was higher in omental fat(36.4+/-6.2 vs. 19.2+/-6.6; P = 0.01), whereas 11betaHSD2 activity was higher in kidney (16.7+/-0.6% vs. 11.3+/-1.5%; p = 0.01). We conclude that greater inactivation of glucocorticoids by 5alpha-reductase in liver and 11betaHSD2 in kidney combined with impaired reactivation of glucocorticoids by 11betaHSD1 in liver may increase the MCR of glucocorticoids and decrease local glucocorticoid concentrations at these sites. By contrast, enhanced 11betaHSD1 in omental adipose tissue may increase local glucocorticoid receptor activation and promote obesity.
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PMID:Understanding the role of glucocorticoids in obesity: tissue-specific alterations of corticosterone metabolism in obese Zucker rats. 1065 Sep 36

Estrogen replacement therapy (ERT) increases a woman's risk of developing endometrial cancer approximately 120% for each 5 years of use. ERT increases a woman's risk of developing breast cancer approximately 10% for each 5 years of use. To reduce the greatly increased endometrial cancer risk, progestins have been added to ERT (estrogen-progestin replacement therapy; EPRT) for between 5 and 15 days (usually 7 or 10 days) per month in a sequential fashion (sequential EPRT; SEPRT) or with each dose of ERT (continuous-combined EPRT; CEPRT). We conducted two large case-control studies in postmenopausal women in Los Angeles to evaluate the effects of these changes on endometrial and breast cancer risks. As expected CEPRT was not associated with any increased risk of endometrial cancer. SEPRT with the progestin being given for 10 days per month also did not increase endometrial cancer risk. SEPRT with the progestin being given for 7 days per month did increase endometrial cancer risk with only a relatively slight reduction in risk compared to ERT effectively proportional to the reduction in the number of days of unopposed estrogen. The sharp contrast between the effects of 7 days and 10 days of progestin in SEPRT suggests that the extent of endometrial sloughing or of 'terminal' differentiation at the completion of the progestin phase may play a critical role in determining endometrial cancer risk. This may provide an explanation of why endometrial cancer risk increases so sharply with age in young women even in countries where obesity-associated anovulation is very uncommon; extended periods of unopposed estrogen is not an explanation but less than 10 days of an 'adequate' progesterone level may be. EPRT significantly increased the risk of breast cancer. EPRT was associated with an approximately 24% increase in risk for each 5 years of use; the effect was some 212-fold greater than the effect of ERT, which we had previously predicted on theoretical grounds. This effect could also be predicted from the results on mammographic densities seen in the PEPI randomized trial of different forms of hormone replacement therapy (HRT). In the PEPI trial EPRT increased mammographic densities to a much greater extent than ERT. Progestins need to be given to protect the endometrium. They need to be delivered to the endometrium in a manner that will have the least effect on the breast. This can be carried out by using a vaginal or direct endometrial route of administration. The vaginal route will provide adequate endometrial progestin levels with low blood levels so that the effects of the progestin on the breast should be small; with the direct endometrial route the blood progestin levels are even lower, and the effects of the progestin on the breast will be effectively zero. If this is unacceptable to a woman, then giving progestins by mouth (or transdermally) for 10 days every 3 to 4 months should provide satisfactory protection of the endometrium when used with standard-dose conjugated estrogen (CE). This regimen has much less effect on the breast than monthly SEPRT or CEPRT. Two clinical trials of 10 mg per day of MPA for 14 days every 3 months and 0.625 mg/day of CE have been published. Both studies suggest that this approach may be satisfactory in that the extent of hyperplasia was minimal. More studies of this approach are urgently needed.
Steroids
PMID:Progestins and menopause: epidemiological studies of risks of endometrial and breast cancer. 1110 73

There is scarce information about the factors associated with estrogen receptors (ER) at menopause. In 113 volunteers pre- and post-menopausal healthy women, grouped as with and without obesity, estrogen receptors-alpha and -beta, and progesterone receptor (PR) were measured by immunohistochemistry in skin punch biopsies obtained from the external gluteal area. In pre-menopausal women, biopsies and a blood sample were performed between days 7 and 14 of the cycle. Serum hormone levels were measured by immunoradiometric assay or radioimmunoassay. After menopause, ER and PR amounts decreased significantly. At pre-menopause, obese women had lower PR levels than non obese (P<.006). In the post-menopausal group, obese women showed higher ER-alpha (P<.03) and ER-beta (P<.02) levels than the non obese group. In the analysis of factors associated with the amount of steroid receptors for the total group, log[ER-alpha], log[ER-beta], and log[PR] were associated with age (P<.002, <.005, and <.004, respectively). The log[ER-alpha] was also associated with log[FSH] (P<.0008); meanwhile, the log[PR] showed a marginal correlation with log[FSH]. In pre-menopausal women no factor associated with any of the three receptors was found. In post-menopausal women log[ER-alpha] was associated with log[estrone] and log[DHEAS] (P<.003 and <.02, respectively). log[PR] was associated with BMI (P<.002), years since menopause (P<.05), and log[DHEAS] (P<.003). We concluded that ER and PR diminish sharply at post-menopause. At this stage the amount of receptors depends on several factors such as BMI, years since menopause, and androgen precursors.
Steroids 2006 Jun
PMID:Factors associated with estrogen receptors-alpha (ER-alpha) and -beta (ER-beta) and progesterone receptor abundance in obese and non obese pre- and post-menopausal women. 1656 54

We examined plasma and fat tissue sex steroid levels in a sample of 28 men aged 24.8-62.2 years (average BMI value of 46.3 +/- 12.7 kg/m(2)). Abdominal adipose tissue biopsies were obtained during general or obesity surgery. Omental and subcutaneous adipose tissue steroid levels were measured by gas chromatography and chemical ionization mass spectrometry after appropriate extraction procedures. BMI and waist circumference were negatively correlated with plasma testosterone (r = -0.49 and -0.50, respectively, p < 0.01) and dihydrotestosterone (r = -0.58 and -0.56, respectively, p < 0.01), and positively associated with estrone levels (r = 0.64 and 0.62, respectively, p < 0.001). Regional differences in adipose tissue steroid levels were observed for dihydrotestosterone (p < 0.005), androstenedione (p < 0.0001) and dehydroepiandrosterone levels (p < 0.05), which were all significantly more concentrated in omental versus subcutaneous fat. Positive significant associations were found between circulating level of a steroid and its concentration in omental and subcutaneous adipose tissue, for estrone (r = 0.72 and 0.57, respectively, p < 0.01), testosterone (r = 0.66 and 0.58, respectively, p < 0.01) and dihydrotestosterone (r = 0.58 and 0.45, respectively, p < 0.05). Positive correlations were observed between plasma dehydroepiandrosterone-sulfate and omental (r = 0.56, p < 0.01) as well as subcutaneous adipose tissue dehydroepiandrosterone level (r = 0.38, p = 0.05). Positive significant associations were found between omental adipocyte responsiveness to positive lipolytic stimuli (isoproterenol, dibutyryl cyclic AMP and forskolin) and plasma or omental fat tissue androgen levels. In conclusion, although plasma androgen or estrogen levels are strong correlates of adipose tissue steroid content both in the omental and subcutaneous fat depots, regional differences may be observed. Androgen concentration differences in omental versus subcutaneous adipose tissue suggest a depot-specific impact of these hormones on adipocyte function and metabolism.
Steroids 2006 Aug
PMID:Omental and subcutaneous adipose tissue steroid levels in obese men. 1676 84

The loss of estrogen associated with menopause is suspected to play an important regulatory role in changes of fat metabolism and obesity. To evaluate the relationship between obesity and the ratio of estrogen receptor subtypes (ERalpha/ERbeta) in adipose tissues in pre- and postmenopausal women, we measured the anthropometric indices of 31 premenopausal women and 12 postmenopausal women. Serum samples, subcutaneous and omental adipose tissues were also obtained from study participants. Serum leptin, adiponectin, IL-6, and TNF-alpha levels were measured using ELISA methods. Real-time RT-PCR analysis was performed to detect and to compare mRNA levels of leptin and estrogen receptor subtypes (ERalpha and ERbeta) from adipose tissues. The ratio of abdominal subcutaneous to omental adipose tissue for the ER subtypes (Sc-Om ratio of the ER subtypes), i.e., subcutaneous ERalpha/ERbeta over omental ERalpha/ERbeta, showed significant correlations with anthropometric indices including BMI (r=0.801, p<0.05) and waist circumference (r=0.696, p<0.05) in both pre- and postmenopausal women. The Sc-Om ratio of the ER subtypes also had a significant correlation with the serum leptin level (r=0.735, p<0.05) as well as the mRNA level of leptin in omental adipose tissue (r=0.753, p<0.05). However, there were no significant differences between the pre- and postmenopausal groups with regard to the expressed level of ER subtypes. In conclusion, our study results showed that the ratio of ERalpha to ERbeta in adipose tissue was associated with obesity as well as the serum level and production of leptin in omental adipose tissue.
Steroids 2007 Jun
PMID:The ratio of estrogen receptor alpha to estrogen receptor beta in adipose tissue is associated with leptin production and obesity. 1750 33


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