estrone-sulfate and Obesity

Accumulation of excess body fat increases breast cancer risk after menopause. Whether the localized breast is differently influenced by adipose tissue compared to the rest of the body, has not been well studied. Our purpose was to demonstrate feasibility and preliminarily evaluate serum-based and localized breast biomarker changes resulting from a weight loss intervention among obese postmenopausal women.. We conducted a 12-week pilot controlled dietary and exercise intervention among healthy obese postmenopausal women, collected serum and breast ductal fluid before and after the intervention, and estimated the association with systemic and localized biomarker changes. We recruited 7 obese (mean body mass index = 33.6 kg/m2) postmenopausal women. We collected samples at baseline and the 12th week for: anthropometry; phlebotomy; dual-energy x-ray absorptiometry (lean and fat mass); exercise fitness (maximum oxygen consumption (VO2Max); 1-repetition strength maximum); and breast ductal lavage.. Changes from baseline occurred in body composition and exercise performance including fat mass loss (14% average drop), VO2Max (+36% increase) and strength improvement (+26%). Breast ductal fluid markers declined from baseline with estradiol showing a 24% reduction and IL-6 a 20% reduction. We also observed serum biomarker reductions from baseline including leptin (36% decline), estrone sulfate (-10%), estradiol (-25%), and Il-6 (-33%).. Conduct of the diet and exercise intervention, collection of ductal fluid, and measurement of hormones and cytokines contained in the ductal fluid were all feasible. We preliminarily demonstrated estradiol and IL-6 reductions from baseline in both serum and breast ductal fluid among obese postmenopausal women who participated in the 12-week weight loss diet and exercise intervention.

Topics: Absorptiometry, Photon; Biomarkers; Body Composition; Body Mass Index; Diet; Diet, Reducing; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Estradiol; Estrogens; Estrone; Exercise; Fatty Acids; Feasibility Studies; Female; Fruit; Humans; Interleukin-6; Leptin; Middle Aged; Obesity; Oxygen Consumption; Phlebotomy; Pilot Projects; Postmenopause; Vegetables; Weight Loss

Excessive glucose production by the liver contributes significantly to diabetic hyperglycemia. The enzyme system glucose-6-phosphatase plays a key role in regulating hepatic glucose production and therefore its inhibition is a potential therapeutic target for the correction of hyperglycemia. It has previously been shown that sulfated steroids, such as estrone sulfate and dehydroepiandrosterone sulfate, inhibit the glucose-6-phosphatase system in vitro, principally through inhibition of endoplasmic reticulum glucose-6-phosphate transport. We report here that in the obese/diabetic ob/ob mouse model, orally administered estrone sulfate reduces the abnormally elevated hepatic glucose-6-phosphatase enzyme activity and enzyme protein levels that are characteristic in the ob/ob mouse, and that this reduction is associated with normalization of blood glucose levels. Other sulfated and non-sulfated steroids also reduced, to a lesser extent, glucose-6-phosphatase enzyme activity - with the exception of dehydroepiandrosterone sulfate, which had no apparent effect on this system in ob/ob mice. Estrone sulfate is therefore an effective antihyperglycemic agent in ob/ob mice, and the glucose-6-phosphatase system can be successfully targeted for the therapeutic management of hyperglycemia in this animal model of non-insulin-dependent diabetes mellitus.

Topics: Aging; Animals; Blood Glucose; Dehydroepiandrosterone Sulfate; Diabetes Mellitus; Estradiol; Estrone; Female; Glucose-6-Phosphatase; Hypoglycemic Agents; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Microsomes, Liver; Obesity

The 24 h mean plasma concentrations of estrone sulfate (ES) were measured in 27 healthy obese and nonobese men (BMI: 21.2-89.5). Plasma levels of ES were found to be elevated in obese men, with ES values significantly correlated to the level of obesity (r = 0.60; P less than 0.001). Thus, an increase in plasma ES concentration (from 524 to 1115 pg/ml), compared to the less than 40 percent increases previously found for estrone and estradiol. Because ES is normally present at an approximately tenfold greater concentration than either estrone or estradiol in men, it may serve as a more easily measurable indicator of adipose tissue aromatization of androstenedione.

Topics: Adipose Tissue; Adult; Androstenedione; Estrogens; Estrone; Humans; Male; Middle Aged; Obesity

Topics: Aged; Aging; Castration; Circadian Rhythm; Estrone; Female; Humans; Male; Menopause; Middle Aged; Obesity; Radioimmunoassay