RESUMEN
BACKGROUND: Mammographic density and sex hormone levels are strong risk factors for breast cancer, but it is unclear whether they represent the same aetiological entity or are independent risk factors. METHODS: Within the Breakthrough Generations Study cohort, we conducted a case-control study of 265 postmenopausal breast cancer cases and 343 controls with prediagnostic mammograms and blood samples. Plasma was assayed for oestradiol, testosterone and sex hormone-binding globulin (SHBG) concentrations and mammographic density assessed by Cumulus. RESULTS: Oestradiol and testosterone were negatively and SHBG positively associated with percentage density and absolute dense area, but after adjusting for body mass index the associations remained significant only for SHBG. Breast cancer risk was independently and significantly positively associated with percentage density (P=0.002), oestradiol (P=0.002) and testosterone (P=0.007) levels. Women in the highest tertile of both density and sex hormone level were at greatest risk, with an odds ratio of 7.81 (95% confidence interval (CI): 2.89-21.1) for oestradiol and 4.57 (95% CI: 1.75-11.9) for testosterone and high density compared with those who were in the lowest tertiles. The cumulative risk of breast cancer in the highest oestradiol and density tertiles, representing 8% of controls, was estimated as 12.8% at ages 50-69 years and 19.4% at ages 20-79 years, and in the lowest tertiles was 1.7% and 4.3%, respectively. Associations of breast cancer risk with tertiles of mammographic dense area were less strong than for percentage density. CONCLUSIONS: Endogenous sex hormone levels and mammographic density are independent risk factors for postmenopausal breast cancer, which in combination can identify women who might benefit from increased frequency of screening and chemoprophylaxis.
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Neoplasias de la Mama/epidemiología , Estradiol/sangre , Glándulas Mamarias Humanas/anomalías , Posmenopausia , Testosterona/sangre , Adulto , Anciano , Densidad de la Mama , Neoplasias de la Mama/sangre , Estudios de Casos y Controles , Femenino , Humanos , Persona de Mediana Edad , Posmenopausia/sangre , Posmenopausia/fisiología , Factores de Riesgo , Globulina de Unión a Hormona Sexual/análisis , Adulto JovenRESUMEN
BACKGROUND: Aromatase inhibitors (AIs) may promote ovarian function recovery (OFR). True incidence, predictors and impact on the outcome of OFR are unknown. PATIENTS AND METHODS: We carried out a prospective study to assess ovarian function in estrogen receptor (ER)-positive BC patients on tamoxifen who had at least 2 years of chemotherapy-induced amenorrhea (CIA) and postmenopausal E2 levels. Patients switched to exemestane and underwent a series of investigations including vaginal ultrasound, antimullerian hormone, follicle stimulating hormone (FSH), and E2. E2 measurements were made using a clinical assay (direct) and a highly sensitive (indirect) immunoassay for comparison. RESULTS: Both E2 assays (indirect versus direct) showed a similar incidence of OFR 32% (95% CI 19.5-44.5) versus 30% (95% CI 17.7-42.3) and median time to OFR 5.4 months (95% CI 1.2-9.6) versus 6.0 months (95% CI 4.8-7.1).On multivariate analysis, the mean age at the start of exemestane treatment was the only marker associated with probability of OFR (OR: 0.44, 0.24-0.78; P = 0.006). According to a receiver operating characteristic (ROC) analysis, age <48 years predicted for OFR (sensitivity: 59%; 1-specificity: 17%; AUC: 0.796; P = 0.001). Patients with OFR had higher mean E2 levels (43.6 versus 5.76 pmol/l; P = 0.001) and a reduced disease-free survival [DFS; HR 9.3 (95% CI 3.3-48.0; P = 0.04)] than those without it. CONCLUSION: Even with a clinical and biochemical profile compatible with menopause, switching from tamoxifen to an AI should be avoided in patients <48 with CIA.
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Amenorrea/inducido químicamente , Androstadienos/uso terapéutico , Antineoplásicos Hormonales/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Ovario/fisiopatología , Tamoxifeno/efectos adversos , Adulto , Amenorrea/mortalidad , Amenorrea/fisiopatología , Antineoplásicos Hormonales/uso terapéutico , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/mortalidad , Supervivencia sin Enfermedad , Sustitución de Medicamentos , Estradiol/sangre , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Menstruación/efectos de los fármacos , Persona de Mediana Edad , Ovario/efectos de los fármacos , Estudios Prospectivos , Curva ROC , Recuperación de la Función , Tamoxifeno/uso terapéutico , Resultado del TratamientoAsunto(s)
Inhibidores de la Aromatasa/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Estradiol/administración & dosificación , Enfermedades Urogenitales Femeninas/inducido químicamente , Enfermedades Urogenitales Femeninas/tratamiento farmacológico , Administración Intravaginal , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/enzimología , Femenino , Enfermedades Urogenitales Femeninas/enzimología , Enfermedades Urogenitales Femeninas/patología , HumanosRESUMEN
BACKGROUND: In postmenopausal women estrogens can be formed by the aromatase pathway, which gives rise to estrone, and the steroid sulfatase (STS) route which can result in the formation of estrogens and androstenediol, a steroid with potent estrogenic properties. Aromatase inhibitors, such as anastrozole, are now in clinical use whereas STS inhibitors, such as STX64, are still undergoing clinical evaluation. STX64 was recently shown to block STS activity and reduce serum androstenediol concentrations in postmenopausal women with breast cancer. In contrast, little is known about the effects of aromatase inhibitors or anti-estrogens on STS activity or serum androgen levels. PATIENTS AND METHODS: Study 1: Blood was collected from ten postmenopausal women with breast cancer before and after two-week treatment with anastrozole and serum concentrations of androstenediol and other androgens and estrogens were assessed. Study 2: Blood samples were collected from 15 breast cancer patients before and after four-week treatment with anastrozole and 10 patients before and after four-week treatment with tamoxifen. Blood was used to assess STS activity in peripheral blood lymphocytes (PBLs) and serum dehydroepiandrosterone sulfate and dehydroepiandrosterone levels. RESULTS: Neither anastrozole nor tamoxifen had any significant effect on STS activity as measured in PBLs. Anastrozole did not affect serum androstenediol concentrations. CONCLUSION: Anastrozole and tamoxifen did not inhibit STS activity and serum androstenediol concentrations were not reduced by aromatase inhibition. As androstenediol has estrogenic properties, it is possible that the combination of an aromatase inhibitor and STS inhibitor may give a therapeutic advantage over the use of either agent alone.
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Andrógenos/sangre , Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/sangre , Neoplasias Hormono-Dependientes/sangre , Nitrilos/uso terapéutico , Esteril-Sulfatasa/metabolismo , Tamoxifeno/uso terapéutico , Triazoles/uso terapéutico , Anastrozol , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/enzimología , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Neoplasias Hormono-Dependientes/enzimología , PosmenopausiaRESUMEN
Trials have shown superiority of aromatase inhibitors (AIs) over tamoxifen for post-menopausal oestrogen receptor-positive advanced breast cancer (ER+ABC). We previously reported the use of goserelin plus anastrozole (G+A) as second-line endocrine therapy for pre-menopausal ER+ABC. We report clinical and endocrine data from G+A as first-line systemic therapy. Thirty-six patients (median age=44 years) with metastatic (N=28) and locally advanced disease were administered G+A for ≥6 months (unless progressed prior). Some (N=13) received further therapy with goserelin plus another AI (steroidal), exemestane (G+E). Serial serum hormone assays (oestradiol, dehydroepiandrosterone sulphate, testosterone, follicle stimulating hormone and luteinising hormone) were performed. Twenty-four patients (67%) derived clinical benefit (CB) (5% complete response, 31% partial response, 31% stable disease for ≥6 months) with median time to progression and duration of CB of 12 (2-47) and 24+(7-78+) months respectively. Ten patients were still receiving first-line G+A at analysis. Amongst 13 patients who went onto receive G+E, 38% achieved CB with a mean duration of 13+(7-32) months. Therapy was well tolerated with no withdrawals. The combination of G+A resulted in 98% reduction (from pre-treatment to 6-month) in median levels of oestradiol (from 574.5 pmol/L; inter-quartile range (IQR)=209-1426; (N=6) to 13.45 pmol/L; IOQ=5.5-31.5 (N=4) whilst the levels of other hormones had minimal fluctuations during therapy. The combinations of ovarian function suppression (using G) and AIs produce sustained CB and minimal side effects in pre-menopausal ER+ABC with significant reduction in oestradiol levels. Within the limitations of being a non-randomised study, they should be considered in appropriate patients with hormone-sensitive ABC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Ovario/efectos de los fármacos , Adulto , Anastrozol , Androstadienos/administración & dosificación , Inhibidores de la Aromatasa/administración & dosificación , Femenino , Hormona Liberadora de Gonadotropina , Goserelina/administración & dosificación , Hormonas/metabolismo , Humanos , Persona de Mediana Edad , Nitrilos/administración & dosificación , Premenopausia , Tamoxifeno/administración & dosificación , Triazoles/administración & dosificaciónRESUMEN
Several adjuvant endocrine strategies exist for postmenopausal women with breast cancer. This study compared the effect of two sequences of aromatase inhibitor use [steroidal (exemestane) and non-steroidal (anastrozole)] on serological and pathological biomarkers when given in the neoadjuvant setting to postmenopausal women with breast cancer. Thirty women were assigned to receive exemestane 25 mg or anastrozole 1 mg each given for 8 weeks in a randomized sequence. The effect of this treatment on serum estrone sulfate and estradiol levels, as well as tumor changes in the proliferation biomarker Ki67 were evaluated at baseline, 8 weeks and 16 weeks. WHO clinical response criteria, patient preference, and quality of life were also assessed. Assessable data was available from 28 patients. There were no differences in concentration changes of serum estradiol or Ki67 between patients in the two arms. Overall clinical response rate was 68% (19/28 assessable patients) and clinical benefit was 93% (26/28 assessable patients). There was no significant difference in toxicity or quality of life scores. The majority of patients expressed a personal preference for anastrozole over exemestane. Results suggest that the order of steroidal and non-steroidal aromatase inhibitors has little effect on outcome. The majority of patients express clear preferences for drug treatments.
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Androstadienos/uso terapéutico , Biomarcadores/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Quimioterapia Adyuvante , Nitrilos/uso terapéutico , Triazoles/uso terapéutico , Anciano , Anciano de 80 o más Años , Anastrozol , Inhibidores de la Aromatasa/uso terapéutico , Proliferación Celular , Esquema de Medicación , Estradiol/sangre , Femenino , Humanos , Antígeno Ki-67/biosíntesis , Persona de Mediana Edad , Posmenopausia , Resultado del TratamientoRESUMEN
CONTEXT: Little is known of associations between hip geometry and skeletal regulators. This is important because geometry is a determinant of both hip function and resistance to fracture. OBJECTIVE: We aimed to determine the effects of sex hormone status and other candidate regulators on hip geometry and strength. SUBJECTS AND METHODS: A random sample of 351 women aged 67-79 had two to four hip dual-energy x-ray absorptiometry scans performed over 8 yr of follow-up. Hip structural analysis software was used to measure subperiosteal diameter (PD) and the distance from the center of mass to the lateral cortical margin (d-lat) on three 5-mm-thick cross-sectional regions: narrow neck, intertrochanter, and shaft. Section modulus (Z), bone mineral density (grams per centimeter squared), and an index of bone mineral content (cross-sectional area) were calculated as estimators of bone strength. Serum analytes measured at baseline included SHBG, estradiol, PTH, creatinine, albumin, vitamin D metabolites, and glutamate- and gamma-carboxyglutamate-osteocalcin (OC). A linear mixed model was used to model associations with predictor variables, including testing whether the predictors significantly modified the effect of aging. RESULTS: Aging was associated with increasing PD and d-lat, and higher baseline SHBG significantly modified this effect, in the case of PD, increasing the rates of change at the narrow neck region by 19% for SHBG level 2 sd higher than population mean (P = 0.026). Higher baseline creatinine was independently associated with faster increases in PD and d-lat with aging (P < 0.041). Z declined faster with aging if baseline PTH was higher, and higher albumin had a contrary effect. Z was positively associated with free estradiol and inversely associated with SHBG and glutamate-OC. CONCLUSION: These results show large effects of SHBG on the regulation of proximal femur expansion and bending resistance, probably acting as a surrogate for low bioavailable estrogen. Potentially important effects for fracture resistance in old age were also revealed for PTH, markers related to renal function and the nutritional markers albumin and undercarboxylated OC.
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Envejecimiento/metabolismo , Fémur/anatomía & histología , Hormonas Esteroides Gonadales/sangre , Anciano , Densidad Ósea , Femenino , Humanos , Osteocalcina/sangre , Hormona Paratiroidea/sangre , Globulina de Unión a Hormona Sexual/análisisRESUMEN
BACKGROUND: Aromatase inhibitors (AI) are increasingly used in early breast cancer and there is a growing interest in associated long-term side-effects of profound estrogen suppression. Urogenital side-effects due to atrophic vaginitis are often managed with vaginal estrogen preparations. These are generally perceived to result in minimal systemic absorption of estrogen. We followed serum estradiol, follicle stimulating hormone (FSH) and luteinising hormone (LH) levels in seven postmenopausal women using vaginal estrogen preparations whilst on AIs for breast cancer. PATIENTS AND METHODS: Serum was analysed for estradiol, FSH and LH at baseline then 2, 4, 7-10 and 12 weeks since commencement of vaginal estradiol. Estradiol was measured on an assay specifically developed for measuring low levels in postmenopausal women. RESULTS: Serum estradiol levels rose from baseline levels < or = 5 pmol/l consistent with AI therapy to a mean 72 pmol/l at 2 weeks. By 4 weeks this had decreased to < 35 pmol/l in the majority (median 16 pmol/l) although significant further rises were seen in two women. CONCLUSIONS: The vaginal estradiol tablet Vagifem significantly raises systemic estradiol levels, at least in the short term. This reverses the estradiol suppression achieved by aromatase inhibitors in women with breast cancer and is contraindicated.
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Inhibidores de la Aromatasa/uso terapéutico , Estradiol/administración & dosificación , Posmenopausia , Vagina , Contraindicaciones , Vías de Administración de Medicamentos , Interacciones Farmacológicas , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Hormona Luteinizante/sangre , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
AIM/HYPOTHESIS: Increased proximal renal sodium re-absorption is associated with central adiposity and insulin resistance in white men. Our study examined whether this association also exists in other ethnic groups with different prevalences of insulin resistance and associated metabolic abnormalities. METHODS: We studied the association between fractional renal excretion of endogenous lithium (FELi) and metabolic syndrome in a population study of 1190 randomly selected men and women who where 40 to 59 years of age (426 white, 397 of African and 367 of South Asian origin). Anthropometric values, blood pressure, biochemical values, questionnaire data and timed urine collections were obtained with standardised techniques. Endogenous lithium in serum and urine was measured by absorption spectrophotometry. Metabolic markers were the homeostasis model assessment (HOMA) index, waist circumference, serum triglycerides, serum HDL cholesterol and metabolic syndrome as defined by Adult Treatment Panel III criteria. RESULTS: In white men and women a higher rate of proximal sodium re-absorption was inversely associated with higher waist circumference, serum triglycerides and HOMA index, and with lower serum HDL cholesterol (all p< or =0.001). No associations were found in people of African or South Asian origin. The former had lower FELi than the other groups. White people with the metabolic syndrome had a lower FELi than those without (15.9% vs 19.0%; p=0.003). No difference was found in people of African or South Asian origin. CONCLUSIONS/INTERPRETATION: Increased proximal sodium re-absorption is associated with the metabolic syndrome in white men and women. This relationship is not seen in people of African or South Asian origin, despite a greater degree of insulin resistance.
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Etnicidad , Riñón/fisiología , Síndrome Metabólico/epidemiología , Sodio/orina , Adulto , África/etnología , Asia/etnología , Glucemia/metabolismo , Presión Sanguínea , Índice de Masa Corporal , Colesterol/sangre , Inglaterra/epidemiología , Femenino , Humanos , Resistencia a la Insulina/fisiología , Riñón/fisiopatología , Litio/farmacocinética , Masculino , Síndrome Metabólico/metabolismo , Síndrome Metabólico/fisiopatología , Persona de Mediana Edad , Triglicéridos/sangreRESUMEN
In vitro evidence suggests that the 'recycling' of K(+) ions through luminal K(+) channels in the thick ascending limb of the loop of Henle (TALH) is essential for the normal operation of the luminal Na(+)-K(+)-2Cl(-) co-transporter. In the present study these channels were investigated in vivo by perfusing superficial loops of Henle in anaesthetised rats with and without the K(+) channel blocker barium. Using a standard perfusate, intraluminal barium (5 mmol l(-1)) reduced sodium reabsorption (J(Na)) from 1887 +/- 50 to 1319 +/- 53 pmol min(-1) (P < 0.001). When the experiment was repeated using a low-Na(+) perfusate, designed to inhibit reabsorption in the pars recta (the initial segment of the loop of Henle), a similar reduction in J(Na) was observed (from 698 +/- 47 to 149 +/- 23 pmol min(-1), P < 0.001), strongly suggesting that the effect of barium is localised to the TALH. The magnitude of the reduction in J(Na) during blockade of K(+) channels confirms the importance of K(+) recycling in facilitating Na(+) reabsorption in the TALH in vivo. However, the reduction in J(Na) was not associated with a fall in the K(+) concentration of the fluid collected at the early distal tubule. When bumetanide, an inhibitor of the Na(+)-K(+)-2Cl(-) co-transporter, was included in the low-Na(+) perfusate, net K(+) secretion was observed. Addition of barium to this perfusate reduced, but did not abolish, the secretion, suggesting that bumetanide-induced K(+) secretion results partly from paracellular transport. Experimental Physiology (2001) 86.4, 469-474.
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Bario/farmacología , Asa de la Nefrona/metabolismo , Bloqueadores de los Canales de Potasio , Potasio/farmacocinética , Sodio/farmacocinética , Animales , Presión Sanguínea , Bumetanida/farmacología , Diuréticos/farmacología , Asa de la Nefrona/efectos de los fármacos , Masculino , Perfusión , Canales de Potasio/metabolismo , Ratas , Ratas Sprague-Dawley , Agua/metabolismoRESUMEN
BACKGROUND: The study of ion transport along the renal tubule in vivo or in vitro requires a technique capable of analyzing ion concentrations in sample volumes of only a few nanoliters. This article describes a method for the analysis of cations at physiological concentrations in samples of tubular fluid taken from single renal tubules in vivo. Method. A background electrolyte composed of 2-[N-Morpholino] ethane-sulfonic acid (MES) (50 mmol/liter) and L-histidine (50 mmol/liter; pH congruent with 6.2), with the additives 18-crown-6 (1 mmol/liter) and methanol (30%) was used for the cation separation combined with conductivity detection. RESULTS: Capillary zone electrophoresis was used to separate NH4, K, Na, Ca, Li, Mg, and Ba in six minutes. Simultaneous quantitative analysis was performed for sodium and potassium, providing detection limits of 0.2 pmol for sodium and 30 fmol for potassium. The calibration plots were linear over three orders of magnitude, including the range of interest to clinical analysis. Data on the reproducibility and repeatability of peak areas and of the repeatability of migration times are reported. CONCLUSION: The results for sodium and potassium are in close agreement with those obtained by atomic absorption spectrometry, indicating that this is a suitable technique for the routine measurement of these cations in tubule fluid samples.
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Líquidos Corporales/química , Cationes/análisis , Electroforesis Capilar , Túbulos Renales/metabolismo , Automatización , Calibración , Electrólitos/análisis , Electroforesis Capilar/instrumentación , Potasio/análisis , Reproducibilidad de los Resultados , Sodio/análisis , Espectrofotometría Atómica , Factores de TiempoRESUMEN
1. In order to examine the electrochemical gradient for potassium reabsorption across the S2 segment of the proximal convoluted tubule, transepithelial potential differences and transepithelial potassium concentrations were measured in anaesthetized potassium-replete and potassium-depleted rats. 2. Potassium-depleted rats were markedly hypokalaemic (plasma potassium, 1.4 +/- 0.1 vs. 4.1 +/- 0.1 mmol l-1 in potassium-replete rats) and had a significantly reduced muscle potassium content. In confirmation of previous reports, glomerular filtration rate was slightly reduced, while fractional reabsorption in the proximal convoluted tubule was enhanced. 3. In potassium-replete animals, the transepithelial potential difference (PD) at the late proximal convoluted tubule was +2.1 +/- 0.3 mV (lumen positive) and the tubular fluid to plasma ultrafiltrate concentration ratio for potassium (TFK/UFK) at the same site was 1. 03 +/- 0.01. In potassium-depleted rats, there was a striking reversal of the transepithelial PD (to -4.0 +/- 0.4 mV), while the TFK/UFK was increased to 1.19 +/- 0.03. 4. The data from both potassium-replete and potassium-depleted animals are consistent with accumulating evidence that potassium reabsorption in the proximal convoluted tubule is passive in nature and depends partly on diffusion down an electrochemical gradient.
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Túbulos Renales Proximales/metabolismo , Deficiencia de Potasio/metabolismo , Absorción , Animales , Líquidos Corporales/metabolismo , Electroquímica , Electrofisiología , Epitelio/metabolismo , Epitelio/fisiología , Tasa de Filtración Glomerular/fisiología , Hipopotasemia/sangre , Túbulos Renales Proximales/fisiología , Masculino , Potasio/sangre , Potasio/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
The aims of the present study were to investigate the effects of changes in sodium intake in patients with untreated mild essential hypertension on the hormonal (plasma renin activity and aldosterone) and renal tubular responses to short-term hyperinsulinemia as achieved by an oral glucose tolerance test (OGTT). Fourteen patients with essential hypertension (mean age, 46 years; average blood pressure (BP), 151/96 mm Hg) were studied. After a 1 week run-in period on their usual diet they entered a randomized double-blind crossover study of a week of low (10 mmol/day) vs a week of high (350 mmol/day) sodium intake. On the last day of each diet they underwent a standard 2-h OGTT. Blood and urines were taken hourly and segmental tubular sodium handling was assessed by the endogenous lithium clearance. The results demonstrate that the plasma insulin and glucose response to a short-term oral glucose load were not influenced significantly by the changes in dietary sodium intake. However, the glucose load was associated with marked renal sodium retention in the absence of any change in systemic BP. The reduction in renal sodium excretion was independent of circulating aldosterone but appeared to be due to an increase in renal distal tubular re-absorption.
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Dieta Hiposódica/normas , Prueba de Tolerancia a la Glucosa/métodos , Glucosa/análisis , Hipertensión/etiología , Hipertensión/fisiopatología , Riñón/metabolismo , Sodio/metabolismo , Sodio/orina , Adolescente , Adulto , Aldosterona/sangre , Péptido C/sangre , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Hiperinsulinismo/fisiopatología , Insulina/sangre , Masculino , Persona de Mediana Edad , Renina/sangreRESUMEN
We compared endogenous with exogenous lithium clearance (CLi) and studied the effects of dietary salt intake on endogenous CLi in healthy volunteers. Lithium was detectable within a narrow fourfold range in serum and in urine in all 25 subjects studied [serum (n = 25), mean 0.27 +/- 0.02 mumol/l, range 0.13-0.55 mumol/l; urine (n = 20), range 1.49-7.32, mean 4.09 +/- 0.36 mumol/24 h]. Mean clearance and fractional excretion of endogenous lithium were lower (15.2 +/- 2.0 ml/min and 16.4 +/- 2.1%, respectively) compared with results obtained using the exogenous CLi technique (25.5 +/- 1.7 ml/min and 27.9 +/- 2.1%; P < 0.01 and P < 0.05, respectively; n = 17). In a separate group of six normal subjects, absolute (8.7 +/- 2.9 vs. 20.7 +/- 3.8 ml/min) and fractional excretion of lithium (8.3 +/- 2.9 vs. 18.0 +/- 5.1%) were significantly lower on 5 days of low (31 +/- 10 mmol/day) vs. high sodium intake (357 +/- 78 mmol/day; P < 0.05). Use of endogenous CLi precludes the need for lithium tablets. This could be a particular advantage in population studies and permits serial measurement of CLi on different days. Our results show that it is important to take dietary sodium intake into account in studies of endogenous CLi. Lower values for endogenous compared with exogenous CLi could reflect differences in renal handling depending on the plasma lithium concentration. This clearly requires further study.
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Dieta Hiposódica , Litio/sangre , Litio/orina , Femenino , Humanos , Litio/análisis , Masculino , Persona de Mediana Edad , Agua/químicaAsunto(s)
Hipertensión/orina , Túbulos Renales Distales/efectos de los fármacos , Natriuresis/efectos de los fármacos , Nifedipino/farmacología , Sodio en la Dieta/administración & dosificación , Adulto , Anciano , Presión Sanguínea/efectos de los fármacos , Peso Corporal , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Hipertensión/fisiopatología , Túbulos Renales Distales/fisiopatología , Masculino , Persona de Mediana EdadRESUMEN
The activity of 17 beta hydroxysteroid dehydrogenase (170HSD) was measured in adipose tissue adjacent to benign or malignant breast tumours. 170HSD activity was significantly correlated with tumour size in malignant tumours (r = 0.75) but not with benign tumours (r = 0.28). Enzyme activity was reduced in adipose tissue adjacent to tumours obtained from inferior breast quadrants.
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17-Hidroxiesteroide Deshidrogenasas/análisis , Neoplasias de la Mama/enzimología , Tejido Adiposo/enzimología , Adulto , Anciano , Peso Corporal , Neoplasias de la Mama/patología , Estradiol/metabolismo , Estrona/metabolismo , Femenino , Humanos , Persona de Mediana EdadRESUMEN
Of the 24 samples of leiomyoma tissues examined 14 were shown to have aromatase activity in vitro. In contrast only 1 of 12 samples of myometrium had any demonstrable activity. Measurements of tissue oestrogen levels showed no correlation with the amount of aromatase activity although oestradiol levels were consistently higher in the tumour tissues compared with the normal myometrium.
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Aromatasa/metabolismo , Leiomioma/enzimología , Miometrio/enzimología , Oxidorreductasas/metabolismo , Neoplasias Uterinas/enzimología , Androstenodiona/metabolismo , Estradiol/metabolismo , Estrona/análogos & derivados , Estrona/metabolismo , Femenino , Humanos , Colagenasa Microbiana/metabolismoRESUMEN
Using slices of human adipose tissue maintained in medium 199 for 40 h at 37 degrees C, it was observed that in the absence of any other additions, the presence of foetal calf serum (10%) inhibits basal levels of aromatase activity. Including dexamethasone (1 X 10(-7) M) in the medium increases aromatase activity approximately 10-fold in the presence of foetal calf serum but has only a small stimulatory effect in its absence. The combined addition of dexamethasone (1 X 10(-7) M) and human prolactin (0.8 ng/ml) has a marked additional incremental effect in the presence or absence of foetal calf serum. In contrast, the addition of prolactin to the medium without glucocorticoid did not stimulate oestrogen production. The possibility that prolactin could be the substance in foetal calf serum responsible for mediating the stimulatory effect of glucocorticoids on oestrogen production is considered.
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Tejido Adiposo/enzimología , Aromatasa/metabolismo , Dexametasona/farmacología , Oxidorreductasas/metabolismo , Prolactina/farmacología , Androstenodiona/metabolismo , Estrona/biosíntesis , Femenino , Humanos , CinéticaRESUMEN
The activity of 17 beta-hydroxysteroid dehydrogenase and aromatase was studied in adipose tissue taken from women aged between 22 and 83 years with benign or malignant breast lesions. The benign and malignant groups showed no significant differences in the mean activities of either of the enzymes studied. Under the experimental conditions used, the rate of conversion of oestrone to oestradiol varied markedly between subjects (6-169 ng oestradiol/mg protein/h), and there was a positive correlation between oestrone reduction and the total body weight of the tissue donor. In contrast, although the apparent Km for oestradiol (0.1-2.6 mumol/l) was lower than that for oestrone (9-14 mumol/l) the maximum velocity for oestrone production was very low (10-50 pmol/mg protein/h), and there was no obvious correlation with the age or body weight of the tissue donor. Aromatase activity in breast fat was at the lower end of the normal range of activity previously reported for abdominal adipose tissue, and there was no correlation between oestrone production and age or body weight.
Asunto(s)
17-Hidroxiesteroide Deshidrogenasas/metabolismo , Tejido Adiposo/enzimología , Aromatasa/metabolismo , Neoplasias de la Mama/enzimología , Mama/enzimología , Oxidorreductasas/metabolismo , Adulto , Factores de Edad , Anciano , Androstenodiona/metabolismo , Peso Corporal , Estradiol/metabolismo , Estrona/metabolismo , Femenino , Humanos , Persona de Mediana EdadRESUMEN
The action of glucocorticoids on aromatase activity in human adipose tissue has been investigated. Oestrogen production was increased in tissue maintained in the presence of dexamethasone and cortisol. Dexamethasone was effective at concentrations as low as 1 nmol/l. In contrast, over the 40 h incubation period, cortisol was only effective at concentrations in excess of 500 nmol/l, although after conditions of prolonged incubation, induction of aromatase activity was measurable using cortisol concentrations as low as 28 nmol/l. There were apparent variations in both basal levels of aromatic activity and in response to glucocorticoids in adipose tissue taken from various sites within the body.