UMLS:C0028754 - FACTA Search

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Query: UMLS:C0028754 (obesity)
124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adipose tissue undergoes aging process as other tissues and both of quantity and distribution of body fat vary with an older age. Obesity in which body fat accumulates excessively is also influenced by aging. For evaluation of obesity, Kaup's index was most correlated with the thickness of fat tissues. Waist hip ratio (WHR) increased with an older age. From the view point of menarche, a role of body fat in reproductive function was evaluated. Ratio of body fat to body weight in the menarcheal age was between 22 and 24%. The ratio of non-menarcheal girls was smaller than that of the menarcheal of the same age. A proper amount of body fat seemed to be necessary for onset of ovarian function to menstruate. On obesity in reproductive age, two topics were discussed. One was the mechanism of menstrual disorders in obese women, the other complications of pregnancy. Concerning the central mechanism of menstrual disorders, hypothalamic disorders cause overfeeding to obesity and gonadal dysfunction to menstrual disorders because feeding center and control center of gonadal system are located in hypothalamus. For the peripheral mechanism, accumulation of fat soluble steroid hormones in the fat tissue disturbs cyclic state of endocrine fluctuation, and extraglandular estrogen production from androgen by aromatase in adipose tissue causes hyperestrogenism. Besides, hyperandrogenism in obese women was stressed on for a causing factor of menstrual disorders in obesity. Hyperandrogenism of obese women with menstrual disorders was associated with high level of cortisol and was corrected by weight reduction to regularize menstrual cycle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Female obesity in life cycle]. 280 41

Obese men have hyperestrogenemia-induced hypogonadotropic hypogonadism (HHG), due, we believe, to increased rarmatization of adrenal androgens by the increased bulk of aromatase-containing adipose tissue. We studied the effects of corticosuppressive doses of dexamethasone (D) on 24-h mean plasma total and free estradiol (E2), estrone (E1), LH, FSH, total and free testosterone, delta 4-androstenedione (delta 4), and sex-hormone-binding globulin (SHBG) in nine obese men and five normal-weight controls. In the obese men, the following hormones fell: E2 [59 +/- 19 to 39 +/- 11 pg/ml (P less than 0.01)], E1 [93 +/- 41 to 50 +/- 25 pg/ml; (P less than 0.01)], delta 4-androstenedione [120 +/- 80 to 55 +/- 27 ng/dl; (P less than 0.02)]; free E2 [1.6 +/- 0.4 to 1.1 +/- 0.2 pg/ml; (P less than 0.01)], SHBG [12.8 +/- 5.3 to 8.2 +/- 3 nM/l; (P less than 0.04)]. FSH rose from 4.8 +/- 3.2 to 7.6 +/- 4.2 miu/ml (P less than 0.01). LH, total and free testosterone showed no significant change. In the nonobese men, there were decreases in total E2 [(34 +/- 6.8 to 25 +/- 10 pg/ml; P less than 0.04)], SHBG [16.8 +/- 7.5 to 10.4 +/- 2.0 nM/l: P less than .05.], free E2 [0.9 +/- 0.2 to 0.7 +/- 0.3 pg/ml: P less than 0.05], delta 4 [91.4 +/- 3.6 to 33.4 +/- 16.7 ng/dl; P less than .01] and total T [492 +/- 44 to 393 +/- 121 ng/dl; P less than 0.04]. There was no significant change in E1, FSH, LH or free T.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Partial reversal of the hypogonadotropic hypogonadism of obese men by administration of corticosuppressive doses of dexamethasone. 314 62

We have found a number of interesting hormonal abnormalities in obese men and women: 1) Obese women have normal levels of estrone, total estradiol, and total testosterone, but as a consequence of their subnormal levels of SHBG, their levels of free estradiol and free testosterone are significantly elevated. 2) Massive weight loss in obese women (to still elevated weight) results in normalization of the previously elevated free estradiol and free testosterone. 3) Obese women have normal plasma DHEA levels, but a significant, age-invariant decrease of the plasma DHEA/T ratio, which could be due to increased tissue activity of 3 beta-hydroxysteroid dehydrogenase. 4) Massive weight loss produces an age-dependent effect on DHEA levels in obese women: the levels increase to supranormal values in women around age 20, with diminishing increases at higher premenopausal ages and no increase at all at perimenopausal age. 5) Obese men have elevated levels of estrone and both free and total estradiol, and subnormal levels of free and total testosterone and of FSH; all these abnormalities are proportional to the degree of obesity. They also have relatively subnormal LH levels, i.e. normal in the face of hypotestosteronemia. The combination of these findings represents a state of mild hypogonadotropic hypogonadism (HHG), which we believe to be induced by the hyperestrogenemia. 6) Normalization of the estrogen levels of obese men, by suppression of adrenocortical secretion of aromatase substrates or by inhibition of aromatase, tends to normalize the HHG. 7) Massive weight loss in obese men normalizes their HHG without any decrease in plasma estrogen levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hormonal abnormalities in obesity. 329 58

Adipose tissue contains both aromatase and 17 beta-steroid dehydrogenase activity. Therefore, to see whether there was a relationship between obesity and certain parameters of androgen and estrogen metabolism we infused 88 women, mean age 51.1 +/- 0.3 years and mean weight 140 +/- 3 lbs, with 3H-testosterone (T)/14C-estradiol (E2) and 3H-androstenedione (A)/14C-estrone (E1) on separate occasions. Blood samples were obtained during the infusion and all urine was collected for 4 days following the start of the infusion. The blood samples were analyzed for radioactivity as A, T, E1, E2, and dihydrotestosterone (DHT) and the urines were analyzed for radioactivity as E1 and E2. From these data we calculated the percent of A converted to T ([rho]A,TBB = percent of A infused measured as T in the blood), [rho]T,ABB [rho]E1,E2BB, and [rho]E2,E1BB. We also measured the ratio of radioactivity as 3H-DHT to radioactivity as 3H-A (CRA,DHT) and 3H-T (CRT,DHT) during the respective androgen infusions. From the ratio of 3H/14C as estrone or estradiol in the urine following 3H-A or 3H-T infusions, we calculated the percent of A or T that was aromatized to E1 or E2 ([rho]A,E1BM; [rho]T,E2BM). When the data from these women were related to weight or Quetelet's Index (QI = wt/ht2) by unweighted linear regression, the only values that were significantly correlated with weight and QI were [rho]T,E2BM and [rho]A,E1BM; for all other [rho] and CR values there was no correlation with weight or QI. We conclude that peripheral aromatization is positively correlated with adiposity but androgen interconversions and estrogen interconversions are not related to adiposity.
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PMID:Androgen and estrogen metabolism: relationship to obesity. 345 82

Recent treatment strategies have been directed toward blockade of estrogen action or inhibition of estrogen biosynthesis as a means of inducing regression of hormone-dependent breast cancer. The major source of estrogen in postmenopausal women is the peripheral conversion of androstenedione to estrone through the enzyme aromatase. It is known that aromatase activity increases proportionately with degree of obesity in women. To test the importance of this modulatory factor, we correlated body weight with estrogen excretion in our population of patients with breast cancer and found significant relationships. In situ production of estradiol from plasma precursors within breast cancer tissue may provide another source of estrogen. Major enzymes mediating estrogen biosynthesis were found to be present in tumor biopsy specimens. Aromatase activity was found to be present in 48/61 human tumors, sulfatase in 35/35, and 17 beta -hydroxysteroid dehydrogenase in 41/41. One inhibitor of aromatase, aminoglutethimide, has been extensively studied in patients with breast cancer. The additional effects of this drug on cholesterol side-chain cleavage and on 11-hydroxylase activity require coadministration of replacement glucocorticoid in treatment regimens. In pilot trials, 37% of patients experienced objective tumor regression with a combination of 1000 mg aminoglutethimide and 40 mg hydrocortisone daily. In randomized clinical trials with this regimen, aromatase inhibition with aminoglutethimide produced tumor regression with similar frequency as did surgical hypophysectomy, surgical adrenalectomy, or tamoxifen administration. The side effects of aminoglutethimide, including lethargy, skin rash, and ataxia complicate its use even though these problems are generally transient. Regimens of low-dose aminoglutethimide are being developed to reduce these side effects. Low-dose aminoglutethimide appears to block aromatase effectively and to have limited side effects, and is undergoing extensive clinical trial. A more specific aromatase inhibitor, 4-hydroxyandrostenedione, is now also being tested clinically, whereas MDL 18962, another new selective inhibitor, is undergoing study in animals.
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PMID:Inhibition of aromatase as treatment of breast carcinoma in postmenopausal women. 354 61

The present study was designed for exploration of hormonal disturbances underlying common forms of amenorrhea. Polycystic ovary syndrome (PCO) patients and obese amenorrheic subjects had significantly elevated estrone (E1) levels, elevated luteinizing hormone/follicle-stimulating hormone ratios, and an exaggerated luteinizing hormone response to luteinizing hormone-releasing hormone. However, androstenedione (delta 4A), the precursor of E1, was elevated only in PCO. Thus, the E1/delta 4A ratio, which provides an indirect index of aromatase activity in extraglandular sites, was raised in obese subjects as a group but not in PCO subjects. These findings suggest that elevated E1 levels, which give rise to abnormal gonadotropin secretion, arise from increased available androgens in PCO but from an increased effect of aromatase (present in adipose tissue) in obese subjects. Measurement of androgens and the E1/delta 4A ratio provides insights into the relative contributions of hyperandrogenemia and enhanced aromatase activity to the genesis of amenorrhea in these groups. In patients with suppressed estradiol levels associated with hyperprolactinemia or weight loss, follicle-stimulating hormone levels were suppressed, while luteinizing hormone was not elevated. Prolactin excess explains these findings in hyperprolactinemia. Plasma E1 levels and the E1/delta 4A ratio were suppressed in patients with weight loss, possibly as a consequence of reduced adiposity. This finding suggests that hypothesis that a minimum level of E1, dependent upon adequate adiposity, is critical for the normal mature function of the hypothalamic-pituitary-ovarian axis. Abnormal E1/delta 4A ratios, high in obesity-associated amenorrhea and suppressed in weight loss-associated amenorrhea, may provide specific markers for these groups of patients.
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PMID:Altered androstenedione and estrone dynamics associated with abnormal hormonal profiles in amenorrheic subjects with weight loss or obesity. 388 79

This article reviews current knowledge of the effect of obesity on ovulation and reproductive potential. Although only a minority of obese women are affected, it seems certain that there is a link between obesity and anovulation. This interrelationship is suggested by the apparent effectiveness of weight reduction in suppressing the hyperandrogenemia observed with obesity and restoring ovulation. The increased aromatase activity and hyperinsulinemia observed in obese women is believed to play a major role in causing the hyperandrogenemia, either by stimulating luteinizing hormone secretion or directly stimulating the ovary. In addition to ovarian hyperandrogenemia, pituitary hypothalamic dysfunction has been observed in response to obesity. Inadequate central serotonin stimulation, excessive dopamine stimulation, and insensitivity to endorphins may all be involved in the pituitary hypothalamic dysfunction, as well as resistance to weight reduction. Few data are available on the efficacy of weight loss in restoring ovulatory function in obese women; nonetheless, weight reduction should be regarded as a central component of any attempt to induce ovulation. In terms of fertility, even a short-term weight loss can be beneficial. Ileal jejunal bypass surgery to effect weight reduction appears to place a fetus at risk; thus, avoidance of pregnancy for at least 2 years after such surgery is advised.
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PMID:Obesity and its effect on reproductive function. 390 6

Adipose tissue is the principal site of estrogen formation in postmenopausal women; with advancing age as well as with increased body weight, there is an increase in the fractional conversion of circulating androstenedione to estrone. We have studied the effects of aging as well as body weight on aromatase activity of adipose tissue specimens taken from 50 women of various ages and weights. Since aromatase activity of adipose tissue is detectable primarily in stromal cells, these cells were incubated with [1-3H]androstenedione (150 nM), and estrogen formation was assayed by measuring the incorporation of tritium into [3H]water. The aromatization rate, when normalized on the basis of equal numbers of cells, increased with increasing age (P less than 0.03; r = 0.43). In contrast, when expressed as a function of body weight, no change in aromatase activity of adipose stromal cells were found. Aromatization of androstenedione by cells from young women who had undergone oophorectomy was not increased compared with that of cells from young women with normal ovarian function, indicating that the onset of menopause per se and the accompanying increase in circulating gonadotropin levels were not causative factors in the increased aromatase activity of adipose stromal cells. We conclude, therefore, that increased estrone production associated with aging may result from an increase in the specific activity of the aromatase enzyme in adipose stromal cells and is not affected by changes in gonadotropin concentrations associated with menopause. On the other hand, the increase in estrogen formation as a function of obesity is probably due to increased numbers of adipose cells, rather than to an increase in the specific activity of aromatase in those cells.
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PMID:Effects of aging and obesity on aromatase activity of human adipose cells. 396 90

It has become conventional wisdom that estrogenic stimulation of breast tissue has something to do with the causation of breast cancer and that the reason obesity is a risk factor for breast cancer is that obese women are hyperestrogenized. However, it has been very difficult to demonstrate that excessive exogenous estrogen increases the incidence of breast cancer, that endogenous estrogen excess is present in breast cancer, or that obese women are hyperestrogenized. We have examined the last question by measuring 24-hr mean plasma estrone and estradiol levels in the midfollicular phase in 18 healthy, regularly cycling, very obese (53 to 218% above ideal weight) women and 16 regularly cycling, age matched, nonobese control women. Unlike obese men, the obese women showed no significant elevation of either estrone or estradiol. Their average estrone level was 72 compared with 64 pg/ml in controls; their average estradiol level was 65 compared with 57 pg/ml in controls. In the combined group (obese plus nonobese), there was a significant correlation of percentage of deviation from ideal weight with plasma estrone (y = 63 + 0.12x; p less than 0.05) but not with estradiol. This correlation supports the current hypothesis that there is increased androstenedione leads to estrone conversion (i.e., increased aromatase activity) in obesity. The reason plasma estrone levels are not significantly elevated in obese women is that the small amount derived from androstenedione is swamped by the much larger amount derived from ovarian secretion, which is apparently unaffected by obesity. Unless there is increased local formation of estrogens in the breast tissue of obese women, the absence of elevated plasma estrogens in them means that their breasts are not "seeing" increased estrogen levels. Thus, endogenous hyperestrogenization is unlikely to be a causative factor of breast cancer in obese women.U
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PMID:Relationship of obesity to blood estrogens. 708 89

Two long and broad streams of medical literature, from the 1950's to date, have established the existence of two unrelated abnormalities of androgen production in women with breast cancer. One is the genetically determined presence of subnormal production of adrenal androgens (i.e. DHEA and DHEAS) in women with premenopausal breast cancer and their sisters, who are at increased risk for breast cancer. The other is excessive production of testosterone, of ovarian origin, in subsets of women with either premenopausal or postmenopausal breast cancer and women with atypical breast-duct hyperplasia, who are at increased risk for breast cancer; along with the hypertestosteronism, there is frequently chronic anovulation in the premenopausal patients. The combination of ovarian hypertestosteronism and chronic anovulation is characteristic of the polycystic ovary syndrome and is also frequently seen in women with abdominal ("android") obesity; both PCOS and abdominal obesity are known to be characterized by high risk for postmenopausal cancer. The elevated testosterone levels and the increased levels of insulin, IGF-I, and IGF-II that are seen in PCOS and abdominal obesity could favor the development of breast cancer in several ways, all of which have been demonstrated experimentally: binding of testosterone to cancer cells bearing testosterone receptors, with direct stimulation; intratissular aromatization of testosterone to estradiol, with stimulation of estrogen-sensitive cells; stimulation of the production of epithelial growth factor (EGF) by testosterone, with direct mitogenic effect of EGF on cancer cells; stimulation of aromatase by insulin and IGF-I; direct mitogenic stimulation of cancer cells by insulin, IGF-I, and IGF-II; and stimulation by IGF-I and IGF-II of the intratissular reduction of estrone to estradiol. Since PCOS is probably largely genetically determined, and abdominal obesity may also be, the hypertestosteronism of these conditions may represent a second genetically determined hormonal risk factor for breast cancer.
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PMID:Abnormal production of androgens in women with breast cancer. 784 May 9

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