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)

Serum binding capacity of sex-hormone binding globulin (SHBG-BC), steroid concentrations, and secretion patterns of LH and FSH were compared between groups of seven nonobese and seven obese patients with polycystic ovarian disease (PCOD). Obese patients with PCOD differed from those with normal weight in having very low SHBG-BC and elevated serum levels of free and albumin bound testosterone. Compared to healthy women in the follicular phase, both nonobese and obese patients with PCOD showed equally elevated serum levels of androstenedione, estrone, and albumin-bound and free estradiol. Pattern of gonadotropin secretion was studied from blood samples taken at 15 min intervals for 6 h. In 6 patients of both groups low pulses of FSH were found coincidently with pulses of LH. Serum level of LH showed a clear pulsatile pattern in all patients with PCOD, varying from 4.5 to 7.5 pulses per 6 h. The mean pulse rate in the groups of nonobese and obese patients with PCOD was similar, 5.9 pulses per 6 h. In the obese patients the mean LH levels were, however, less elevated and the pulse amplitudes were smaller than those in the nonobese patients. We suggest that this difference is due to high levels of biologically active testosterone in obese patients with PCOD.
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PMID:Obesity, serum steroid levels, and pulsatile gonadotropin secretion in polycystic ovarian disease. 622 11

Insulin resistance (IR) in polycystic ovary syndrome (PCO) has been linked to hyperandrogenism and elevated luteinizing hormone (LH) levels. Fourteen patients with idiopathic hirsutism (IH), 13 with PCO, and 6 control subjects were investigated for assessment of the effects of serum LH, peripheral tissue androgens, and sex hormone-binding globulin (SHBG) on fasting immunoreactive insulin (IRI) levels. Serum LH, dehydroepiandrosterone sulfate, dihydrotestosterone, and 3 alpha-androstanediol, SHBG, and unbound testosterone (uT) were measured. Serum testosterone (T) showed a positive correlation with IRI (P less than 0.05), and SHBG showed a negative correlation (P less than 0.02). Unbound T showed a highly significant positive correlation (P less than 0.001), whereas dehydroepiandrosterone sulfate, dihydrotestosterone, and 3 alpha-androstanediol did not correlate. Gonadotropin-releasing hormone, administered to patients with IH, raised LH levels but did not change IRI levels. Spironolactone did not affect T or IRI in patients with IH but significantly lowered T and IRI in patients with PCO. It is suggested that IR is not related to LH or peripheral androgen metabolism but highly correlated with uT and SHBG, thus coupling two important factors in IR, obesity and the androgen level.
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PMID:The influence of androgens on insulin resistance. 623 Feb 59

In menopause, estrogens are produced almost exclusively through peripheral aromatization of androgens, especially androstenedione. Obesity increases the production rate of estrogens by means of the same mechanism. In postmenopause, plasma levels of SHBG diminish significantly. Obesity even further decreases the levels of SHBG, thus increasing "free" E2 available to target tissues. The increase in circulating estrogenic activity in menopause, whether as a result of obesity or of ingestion of estrogens, implies a risk factor for endometrial and breast cancer not only because of the permissive and stimulating effects of estrogens but also due to the special circumstance that they may act on target tissues in the almost absolute absence of the "protecting effect" of progesterone. The modifications performed by obesity on the values of SHBG and circulating estrogens are reversible, since they tend to normalize with weight loss.
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PMID:Peripheral aromatization as a risk factor for breast and endometrial cancer in postmenopausal women: a review. 631 45

A possible role for increased androgenic/estrogenic activity in the pathogenesis of upper body fat localization and its accompanying cellular and metabolic characteristics was examined. Eighty healthy, nonhirsute, premenopausal, caucasian women with a wide range of body fat topography [waist to hips girth ratio (WHR), 0.64 to 1.02] and obesity level (percentage of ideal body weight, 92-251%) were studied. Increasing androgenicity, as reflected by a decrease in plasma sex hormone-binding globulin capacity and an increase in the percentage of free testosterone, was accompanied by 1) increasing WHR, this relationship being independent of and additive to that of obesity level; 2) increasing size of abdominal, but not femoral, adipocytes; 3) increasing plasma glucose and insulin levels, both basally and in response to oral glucose loading; and 4) diminished in vivo insulin sensitivity, as revealed by increasing steady state plasma glucose levels at comparable plasma insulin levels, attained by the infusion of somatostatin, insulin, and glucose. No association was found between total plasma testosterone, androstenedione, dehydroepiandrosterone sulfate, or estradiol concentrations and WHR, fat cell size, or metabolic profiles. We, therefore, propose that in premenopausal women, a relative increase in tissue exposure to unbound androgens may be responsible in part for localization of fat in the upper body, enlargement of abdominal adipocytes, and the accompanying imbalance in glucose-insulin homeostasis.
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PMID:Relationship of androgenic activity to body fat topography, fat cell morphology, and metabolic aberrations in premenopausal women. 634 69

Comparisons are made of the plasma binding capacity and concentration of sex hormone binding globulin. Concentration was measured by electroimmunodiffusion standardised in terms of mass of the protein and binding capacity by two methods measuring the binding of 5 alpha-dihydrotestosterone. Isolation of steroid bound by SHBG was by either ammonium sulphate precipitation or cellulose filter discs. Both binding methods correlate highly with electroimmunodiffusion indicating they respond similarly to changes in the plasma concentration of the protein. However, they do not equally reflect the actual concentration. Estimates of the molecular mass of the protein of 188000 and 100000 from the precipitation and disc methods respectively, suggest the former measures less of the protein present than does the latter. A parallel reduction in binding capacity and concentration is seen in obese post-menopausal females. This previously unreported finding suggests that the reduced plasma binding capacity of sex hormone binding globulin in obesity is not due to altered or impaired steroid binding.
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PMID:Comparative measurements of plasma binding capacity and concentration of human sex hormone binding globulin. 642 22

Blood production rates of testosterone, dihydrotestosterone (DHT), and 3 alpha-androstanediol (3 alpha-diol) were found to be approximately 2-fold elevated in morbidly obese, nonhirsute, normally menstruating women. Values were intermediate between those found in normal women and those in a group of nonobese normally menstruating women with idiopathic hirsutism. Elevated androgen production rates in obese women were associated with 2- to 3-fold increases in MCRs, presumably due to decreased levels of sex hormone-binding globulin. Thus, increased production rates were offset by increased MCRs, resulting in plasma testosterone, DHT, and 3 alpha-diol concentrations that were similar in the obese and normal women. By contrast, women with hirsutism had increased production rates associated with elevated plasma androgens as well as increased MCRs. Urinary excretion of testosterone glucuronide and 3 alpha-diol glucuronide (3 alpha-diol G) were elevated in both obese and hirsute women, paralleling the increased androgen production rates. Despite increased production rates and excretion of androgens, obese women exhibited no menstrual abnormalities, hirsutism, or other signs of virilism. To explore the apparent ineffectiveness of increased androgen production to produce virilizing symptoms, we measured plasma 3 alpha-diol G levels as a measure of peripheral androgen action. The mean +/- SE plasma 3 alpha-diol G was 53 +/- 8 ng/dl in obese women and 36 +/- 6 in normal women; by contrast, women with idiopathic hirsutism had levels of 440 +/- 99, a 12-fold elevation. Plasma testosterone glucuronide in obese and hirsute women were only 2- to 3-fold elevated, while plasma DHT glucuronide was not increased in obese women and was only 2-fold elevated in hirsute women. Thus, obesity is a state of increased androgen production and accelerated clearance. 3 alpha-diol G levels in obese women were only minimally elevated, in contrast to values in the hirsute women, perhaps reflecting the apparent androgen ineffectiveness.
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PMID:Elevated production and metabolic clearance rates of androgens in morbidly obese women. 648 Aug 13

The important finding was that sex hormone-binding globulin (SHBG) binds 5 alpha-dihydrotestosterone (DHT) with more efficacy than 17 beta-estradiol in patients with breast cancer and that SHBG binds it with less efficacy than 17 beta-estradiol in normal women. An unexpected finding was that there was no correlation between SHBG-binding capacity for 17 beta-estradiol and that for DHT of the same plasma. On the basis of these findings, we confirmed that SHBG-binding capacity for 17 beta-estradiol was a useful predictive index of hormone dependence of human breast cancer. We studied the correlation between SHBG-binding capacity for 17 beta-estradiol and Kaup Index as an index of obesity to examine the interaction between obesity and carcinogenesis of hormone-dependent breast cancer. Significant positive correlation between SHBG-binding capacity for 17 beta-estradiol and Kaup Index was achieved in premenopausal patients. Our results indicate that obesity is an important risk factor for carcinogenesis of hormone-dependent breast cancer.
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PMID:Plasma sex hormone-binding globulin (SHBG) and obesity in breast cancer patients. 668 84

We have measured the plasma concentrations of sex steroids and sex hormone-binding globulin (SHBG) in twenty-three massively obese women and ten age-matched lean female volunteers. In the obese women increased plasma testosterone (obese 3.2 +/- 0.5 nmol/l controls 1.7 +/- 0.5 nmol/l, P less than 0.3) and androstenedione concentrations (obese 9.7 +/- 1.2 nmol/l, controls 4.4 +/- 0.6 nmol/l, P = less than 0.01) an increased ratio of oestrone:oestradiol (obese 2.4 +/- 0.4, controls 1.0 +/- 0.1, P = less than 0.1) and decreased SHBG levels (obese 30 +/- 4 nmol/l, controls 60 +/- 8 nmol/l, P = less than 0.001) were found. Obesity differed from the polycystic ovary syndrome (in which a similar pattern of changes of sex steroid concentrations and binding are seen) in that it was associated with normal increases in serum luteinizing hormone (LH) follicle stimulating hormone (FSH) levels in response to the administration of LHRH. We conclude that the common occurrence of menstrual abnormalities in obesity results from abnormal secretion and binding of sex steroids. In addition, the unaltered secretion of LH and FSH in the presence of such changes is evidence for a disorder of hypothalamic function.
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PMID:Abnormal sex steroid secretion and binding in massively obese women. 676 12

Virilization in women is associated with increased production of testosterone as well as a variety of androgenic prehormones, including androstenedione, androstenediol, DHEA, DHEA-sulfate, dihydrotestosterone and androstanediol. Of these hormones, it is likely that testosterone is the androgen which initiates a series of androgen-receptor mediated events resulting in stimulation of 5 alpha reductase in the skin and hair follicles, producing dihydrotestosterone locally. The metabolism of testosterone to dihydrotestosterone within the hair follicle results in increased clearance of testosterone, however at the expense of hair follicle stimulation. Increased 5 alpha reductase of the skin and hair allows other prehormones to be metabolized to dihydrotestosterone and androstanediol, further stimulating the hair follicle (multiplier effect). In obese women, androgen production rates are elevated and SHBG levels are depressed, in many cases to the same magnitude as that observed in hirsute women. Increased androgen production rates in obesity, however, are associated with major increases in clearance rates of these androgens. Resultant androgen blood levels are even lower than observed in the non-obese population. It appears likely that adipose tissue is the site of the increased clearance rates and metabolism of prehormones to dihydrotestosterone and androstanediol. A delicate balance likely exists between production and clearance of these biologically active hormones. Minor aberrations in this balance may result in the increased incidence of hirsutism seen in the obese female population.
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PMID:A comparison of androgen production and clearance in hirsute and obese women. 688 88

In comparison with matched nonvegetarian women, postmenopausal vegetarian women were found to have lower urinary levels of estriol and total estrogens, lower plasma prolactin levels, and higher plasma sex hormone-binding globulin (SHBG) levels. These differences were not explained by differences in body weight or obesity. Plasma SHBG levels were highly correlated with plasma high-density lipoprotein cholesterol levels, which were also higher in vegetarians than in nonvegetarians. These hormonal differences may explain the lower rates of endometrial and possibly breast cancer that have been observed previously in vegetarian women.
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PMID:Diet and reproductive hormones: a study of vegetarian and nonvegetarian postmenopausal women. 694 45


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