Open Journal of Endocrine and Metabolic Diseases最新文献

Estrogen has various physiological functions and the estrogen receptor (ER) is a key regulator of those functions. ERα is a ligand-dependent transcription factor and that activity is mediated by the transactivating function-1 (AF-1) in the N-terminal domain and transactivating function-2 (AF-2) in the C-terminal ligand-binding domain. The functions of ERα AF-1 and AF-2 have been characterized by various in vitro experiments, however, there is still less information about the in vivo physiological functions of ERα AF-1 and AF-2. Recently, we established a genetically mutated ERα AF-2 knock-in mouse (AF2ERKI) that possesses L543A, L544A mutated-ERα. This AF-2 core mutation disrupted AF-2 function and resulted in ERα null phenotypes. This mouse model revealed that proper AF-2 core structure and function are indispensable for ERα-mediated physiological responses and AF-1 functionality. AF2ER mutation reverses the ERα antagonists to agonists and that activity is mediated by AF-1 solely. The pure antagonist, ICI182780/fulvestrant, activated several estrogen-mediated physiological responses in the AF2ERKI mouse. The AF2ERKI mouse model will be able to discern estrogen physiological functions which involve AF-1.

Background: Obesity is associated with higher end-stage renal disease incidence, but associations with earlier forms of kidney disease remain incompletely characterized.

Methods: We studied the association of body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) with rapid kidney function decline and incident chronic kidney disease in 4573 non-diabetic adults with eGFR ≥ 60 ml/min/1.73m² at baseline from longitudinal Multi-Ethnic Study of Atherosclerosis cohort. Kidney function was estimated by creatinine and cystatin C. Multivariate analysis was adjusted for age, race, baseline eGFR, and hypertension.

Results: Mean age was 60 years old, BMI 28 kg/m², baseline eGFR_Cr 82 and eGFR_Cys 95 ml/min/1.73m². Over 5 years of follow up, 25% experienced rapid decline in renal function by eGFR_Cr and 22% by eGFR_Cys. Incident chronic kidney disease (CKD) developed in 3.3% by eGFR_Cys, 11% by eGFR_Cr, and 2.4% by both makers. Compared to persons with BMI < 25, overweight (BMI 25 - 30) persons had the lowest risk of rapid decline by eGFR_Cr (0.84, 0.71 - 0.99). In contrast, higher BMI categories were associated with stepwise higher odds of rapid decline by eGFR_Cys, but remained significant only when BMI ≥ 35 kg/m² (1.87, 1.41 - 2.48). Associations of BMI with incident CKD were insignificant after adjustment. Large WC and WHR were associated with increased risk of rapid decline only by eGFR_Cys, and of incident CKD only when defined by both filtration markers.

Conclusions: Obesity may be a risk factor for kidney function decline, but associations vary by filtration marker used.

Objectives: While researchers are increasingly recognizing the importance of adjusting waist circumference (WC) for height, no standard has yet been established. In this study we contrast three standard methods for indexing WC by height (using height, root-height and height-squared) via comparisons with age-specific optimal indices.

Study design and setting: Measurements from 722 male and 746 female Caucasian participants in the Fels Longitudinal Study were used. The three standard waist-circumference indices (as well as an optimal index) were determined for ages 2 through 18, and for every decade thereafter to 70 years of age. Pearson correlations were used to assess the suitability of all indices.

Results: The three standard indices remain correlated with the original WC measures, though each was associated with height at some ages. Waist-to-height ratio is suitable for some childhood ages (boys: 5 - 9, 13 - 16; girls: 4 - 7, 9, 11 - 14) but not for adult ages; Root-height works well mostly for older teenage children and adults but not in early childhood and adolescence; Height-squared is nowhere suitable. In both men and women, the optimal indexing factor ranged between root-height and height-squared in childhood, and is close to root-height in adulthood.

Conclusions: No one index is most suitable, as WC indexed by root-height is suitable for use with measurements from teenage children and adults, while waist-to-height ratio is generally suitable for use in children. WC indexed by height-squared is nowhere suitable.