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

An increasing incidence of endometrial cancer caused by a higher life expectancy and a number of other facters (i.e. obesity, diabetes, hypertension, lower pregnancy rate) as well as the unfavorable location for early detection when compared with cervical cancer has initiated this review in order to single out women with increased risk. Clinical characteristics of patients with endometrial cancer represented by age, menstrual disorders, reduced fertility, obesity, diabetes, hypertension, hirsutism, hyperplasia of the ovarian stroma or hilus cells in connection with an increased oestrogen effect in the vaginal smear and proliferative changes of the endometrium can be explained by extraglandular respectively peripheral aromatization of androgens to oestrogens, particular by the conversion of androstenedione to oestrone. This is supported by an increased plasma oestrone/oestradiol-ratio and increased conversion rate with age and overweight. In vivo- and in vitro-investigations have demonstrated the participation of adipose tissue in peripheral oestrogene production. The compiled data point towards the importance of the extraglandular oestrone production for the etiology of endometrial cancer by effecting the endometrium over a long period of time. The counter action of the normally cyclic changes of oestradiol and progesterone is lacking. Therefore, a dysoestrogenic effect of oestrone upon the endometrium can be fully effective, depending on the hormone receptor content of the respective endometrium. Based upon these data including recent publications, pre- and postmenopausal oestrogen therapy has to be critically reevaluated.
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PMID:[Endometrial cancer and extraglandular oestrogen biosynthesis (author's transl)]. 32 98

The factors that increase the risk of development of endometrial cancer are reviewed. Many of these conditions are frequently associated with an elevated production of estrone in peripheral (nonendocrine) tissues from circulating androstenedione. Elevated estrone production may occur in young, anovulatory or postmenopausal women whose ovaries secrete higher than normal amounts of androstenedione. Alternatively, conditions such as obesity and liver disease are associated with higher than normal rates of conversion of androstenedione to estrone, resulting in high estrone levels. Neither the exact tissue site(s) of conversion nor the normal function of this process has yet been established. Much less information concerning steroid hormone receptor measurements in endometrial cancer than in breast cancer is available. However, it seems certain that measurement of progesterone receptors will provide a useful guide in the selection of progestational therapy.
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PMID:Steroid hormones and endometrial cancer. 35 36

The techniques used for determination of hormone receptors have provided a biochemical basis to the concept of hormone-dependence in breast cancer. By medical experience clinical factors were established for determination of hormonal treatment in breast tumors. The criteria used need now to be re-evaluated in terms of hormone receptor contents. We analysed a group of 155 patients with histologically confirmed breast carcinoma in which estradiol receptor determination was performed. Of these tumors 54% had more than 10 fmol of estradiol per mg protein. Menopause, advanced age, late first childbirth, obesity, early menopause and nuliparity were associated, in that order, with the presence of estrogen receptors in breast tumors. Prognostic stratification analysis brought out polar groups of estrogen receptor contents. Young, premenopausal women with children had only 16% estrogen receptor-positive tumors. Postmenopausal women, either without children or with late first childbirth had as much as 81% of estrogen receptor containing tumors. Clinical variables related to the presence of estrogen receptor positive tumors in the breast cancer population were coincident to risk factors for breast cancer in the healthy population. Possible implications of this coincidences are discussed.
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PMID:Clinical factors related to the presence of estrogen receptors in breast cancer: a prognostic stratification analysis. 713 36

A historical prospective study was conducted at the Mercy Hospital of Pittsburgh, Pennsylvania (USA), to study the role of post-menopausal obesity in the recurrence and survival of breast cancer. Records from 301 post-menopausal women diagnosed with breast cancer from 1977 to 1985 were followed for at least 5 years from data supplied by the Tumor Registry and medical records. Data collected included age, height, weight, race, hormone receptor status, stage and size of tumour, number of positive nodes, site of distant metastasis, first course of treatment, and 5 year recurrence and survival. Forty-five per cent of patients were obese (n = 136), while 55% were non-obese (n = 165). Obesity was defined by the Quetelet index (patients with values > 27 were considered obese). The recurrence rates for the obese and non-obese groups were 40% and 39% respectively, and were not significantly different. Univariate and multivariate analyses showed that there was no significant association between obesity in post-menopausal women and likelihood of recurrence of or death from breast cancer.
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PMID:An examination of obesity and breast cancer survival in post-menopausal women. 794 99

In 22 patients with endometrial carcinoma, Stage I-III (mean age 57.8 years) with obesity, initial and reactive hyperinsulinemia (during glucose load) was revealed. Significant correlations between values of "peak" and field-square of the insulin secretion curve and cytoplasmatic receptors to Estradiol and Progesterone in the tumor were found. In a group of the patients with high values of reactive hyperinsulinemia significantly larger amounts of steroid hormone receptors in the tumor were determined as compared to the group of the patients who had low insulinemia values. On considering these data a possible conclusion was reached as to the modifying influence of hyperinsulinemia on sensitivity of endometrial carcinoma to hormone receptor synthesis in the tumor by insulin.
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PMID:Hyperinsulinemia as a factor modifying sensitivity of endometrial carcinoma to hormonal influences. 850 Apr 94

The present study consists of 1,238 women with unilateral breast cancer treated with modified radical mastectomy living in the geographic area of Haukeland Hospital. Their weight and height had been measured years before presentation of the disease. Age-adjusted Quetelet's index (weight/height2) showed that obese women had a 49% higher risk of dying from breast cancer than lean ones. The relative risk decreased slightly when adjusted for tumour diameter, lymph node status, and mean nuclear area of the tumour cells. The prognostic effect of Quetelet's index was examined according to the estrogen and/or progesterone receptor status of the tumour. In patients with a hormone receptor positive tumour, obese women had a risk that was more than three times higher than lean ones. In patients with hormone receptor negative tumour, the effect of obesity was reversed, lean patients having a risk that was more than six times higher than obese ones, even after adjustment for lymph node status, tumour diameter, and mean nuclear area. Quetelet's index, while being a prognostic variable in its own right, thus acts differently in patients with hormone receptor positive and negative tumours.
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PMID:Pre-morbid body-mass-index in breast cancer: reversed effect on survival in hormone receptor negative patients. 894 30

Dominant alleles at the agouti locus (A) cause an obesity syndrome in the mouse, as a consequence of ectopic expression of the agouti peptide. This peptide, normally only found in the skin, is a high-affinity antagonist of the melanocyte-stimulating hormone receptor (MC1-R), thus explaining the inhibitory effect of agouti on eumelanin pigment synthesis. The agouti peptide is also an antagonist of the hypothalamic melanocortin-4 receptor (MC4-R). To test the hypothesis that agouti causes obesity by antagonism of hypothalamic melanocortin receptors, we identified cyclic melanocortin analogues that are potent agonists or antagonists of the neural MC3 (refs 11, 12) and MC4 receptors. Intracerebroventricular administration of the agonist, MTII, inhibited feeding in four models of hyperphagia: fasted C57BL/6J, ob/ob, and A(Y) mice, and mice injected with neuropeptide Y. Co-administration of the specific melanocortin antagonist and agouti-mimetic SHU9119 completely blocked this inhibition. Furthermore, administration of SHU9119 significantly enhanced nocturnal feeding, or feeding stimulated by a prior fast. Our data show that melanocortinergic neurons exert a tonic inhibition of feeding behaviour. Chronic disruption of this inhibitory signal is a likely explanation of the agouti obesity syndrome.
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PMID:Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. 899 Jan 9

The mahogany (mg) locus originally was identified as a recessive suppressor of agouti, a locus encoding a skin peptide that modifies coat color by antagonizing the melanocyte-stimulating hormone receptor or MC1-R. Certain dominant alleles of agouti cause an obesity syndrome when ectopic expression of the peptide aberrantly antagonizes the MC4-R, a related melanocyte-stimulating hormone receptor expressed in hypothalamic circuitry and involved in the regulation of feeding behavior and metabolism. Recent work has demonstrated that mg, when homozygous, blocks not only the ability of agouti to induce a yellow coat color when expressed in the skin of the lethal yellow mouse (AY), but also the obesity resulting from ectopic expression of agouti in the brain. Detailed analysis of mg/mg AY/a animals, presented here, demonstrates that mg/mg blocks the obesity, hyperinsulinemia, and increased linear growth induced by ectopic expression of the agouti peptide. Remarkably, however, mg/mg did not reduce hyperphagia in the AY/a mouse. Furthermore, mg/mg induced hyperphagia and an increase in basal metabolic rate in the C57BL/6J mouse in the absence of AY. Consequently, although mahogany is broadly required for agouti peptide action, it also appears to be involved in the control of metabolic rate and feeding behavior independent of its suppression of agouti.
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PMID:Mahogany (mg) stimulates feeding and increases basal metabolic rate independent of its suppression of agouti. 977 May 50

Insulin degradation is a regulated process that plays a role in controlling insulin action by removing and inactivating the hormone. Abnormalities in insulin clearance and degradation are present in various pathological conditions including type 2 diabetes and obesity and may be important in producing clinical problems. The uptake, processing, and degradation of insulin by cells is a complex process with multiple intracellular pathways. Most evidence supports IDE as the primary degradative mechanism, but other systems (PDI, lysosomes, and other enzymes) undoubtedly contribute to insulin metabolism. Recent studies support a multifunctional role for IDE, as an intracellular binding, regulatory, and degradative protein. IDE increases proteasome and steroid hormone receptor activity, and this activation is reversed by insulin. This raises the possibility of a direct intracellular interaction of insulin with IDE that could modulate protein and fat metabolism. The recent findings would place intracellular insulin-IDE interaction into the insulin signal transduction pathway for mediating the intermediate effects of insulin on fat and protein turnover.
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PMID:Insulin degradation: progress and potential. 979 60

The fat gene in mice represents a recessive mutation at the carboxypeptidase E (Cpe) locus. The mutant allele (Cpe(fat)) encodes a highly unstable enzyme and produces an obesity phenotype characterized by attenuated processing of prohormones such as proinsulin that require this exopeptidase for full maturation. This article presents a preliminary physiologic and endocrinologic characterization of the stock of C57BLKS/LtJ-Cpe(fat)/Cpe(fat) mice at the backcross generation (N10) currently distributed by The Jackson Laboratory. Although previously reported not to be diabetogenic at N5, an additional five backcrosses to the C57BLKS/J background resulted in a male-biased development of both obesity and diabetes. Major differences distinguishing this mutant stock from the phenotypes produced by either the diabetes (Lepr(db)) or obese (Lep(ob)) mutations on the same inbred strain background are lack of hyperphagia and hypercorticism, sensitivity of diabetic males to exogenous insulin, and a milder and male-biased diabetes syndrome that is not associated with widespread beta-cell necrosis and islet atrophy, and that often remits with age.
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PMID:Physiologic and endocrinologic characterization of male sex-biased diabetes in C57BLKS/J mice congenic for the fat mutation at the carboxypeptidease E locus. 1040 72


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