ABSTRACT
BACKGROUND: In males with end stage renal disease biochemical hypogonadism is a frequent finding. Testosterone and sex hormone binding globulin (SHBG) have been associated with insulin resistance, a well-known condition in uremia. The aim of the present study was to investigate in males on chronic hemodialysis the relationship of testosterone and SHBG serum levels with insulin resistance. METHODS: In a cross-sectional study we enrolled men treated with chronic hemodialysis who did not suffer from an acute illness or other endocrinopathy, as well as primary hypogonadism, and were not hospitalised. Diabetes mellitus, diabetic nephropathy or previous transplantation were not exclusion criteria. As controls we used a community-based group of healthy males matched for age and Body Mass Index (BMI). We assessed the BMI (kg/m2) from body weight and height, the body fat content (%) by bioelectrical impedance and serum testosterone (ng/ml), SHBG (nmol/L) and estradiol (pg/ml) by standard methods. Testosterone < 3.25 ng/ml defined biochemical hypogonadism. In non-diabetic males, we calculated the homeostasis model assessment index (HOMA-R), an estimate of insulin resistance, from serum fasting insulin and glucose. RESULTS: 27 men (age 54.4 ± 19 years) on chronic hemodialysis (treatment duration 29.1 ± 14.4 months) and 51 healthy men (age 47.1 ± 9.6 years) were included. In men on hemodialysis vs. healthy men there were increased serum levels of SHBG (40.9 ± 26.9 vs. 27.6 ± 11.9 nmol/L; p = 0.031) and a significantly enhanced frequency of biochemical hypogonadism (22.2 vs. 3.9%; p = 0.011). In cases without diabetes (n = 22) a significant correlation was observed between the HOMA-R (r = -0.586, p = 0.004) and the fasting insulin levels (r = -0.650, p = 0.001) on the one hand and the serum SHBG levels on the other. CONCLUSIONS: Our findings confirm enhanced prevalence of biochemical hypogonadism in males on chronic hemodialysis. In non-diabetic cases the serum levels of SHBG correlated with serum insulin and insulin resistance.
ABSTRACT
Corticotropin-releasing hormone, which is the predominant regulator of neuroendocrine responses to stress, attenuates inflammation through stimulation of glucocorticoid release. Enhanced corticotropin-releasing hormone expression has been detected in inflammatory cells of the vascular endothelium, where it acts as a local regulator of endothelial redox homeostasis. Estrogens have beneficial effects on endothelial integrity and function, though the mechanism underlying their antioxidative effect remains as yet largely unknown. We therefore investigated the effect of 17ß-estradiol on pro-oxidant action of corticotropin-releasing hormone in vitro in macroendothelial cells, and, more specifically, the role of 17ß-estradiol on corticotropin-releasing hormone-induced activities/release of the antioxidant enzymes namely, endothelial nitric oxide synthase, superoxide dismutase, catalase, and glutathione. We observed that 17ß-estradiol abolished the stimulatory effect of corticotropin-releasing hormone on intracellular reactive oxygen species levels and counteracted its inhibitory effect on endothelial nitric oxide synthase activity and nitric oxide release. In addition, 17ß-estradiol significantly induced superoxide dismutase and catalase activity, an effect that was not significantly influenced by corticotropin-releasing hormone. Finally, 17ß-estradiol significantly increased glutathione levels and the glutathione/glutathione + glutathione disulfide ratio, an action that was partially blocked by corticotropin-releasing hormone. Our results reveal that 17ß-estradiol counterbalances corticotropin-releasing hormone-mediated pro-inflammatory action and thereby maintains the physiological threshold of the endothelial cell redox environment. These observations may be of importance, considering the protective role of estrogen in the development of atherosclerosis.
ABSTRACT
OBJECTIVE: Plasma total adiponectin reveals a sexual dimorphism indicating that gonadal steroids may be involved in its secretion and/or metabolism. However, results from previous reports are conflicting and data regarding the influence of ovarian steroids on adiponectin's multimer forms are scarce. The objective of the study was to assess if total adiponectin and its isoforms are affected by the changes of estradiol and progesterone during the normal menstrual cycle and the association of total adiponectin and its isoforms with the gonadal steroid levels. MATERIALS/METHODS: Quantitative determination of plasma adiponectin and its multimers was conducted in the three phases of an ovulatory cycle in 13 premenopausal women, in the follicular phase of 10 more premenopausal women, in 20 postmenopausal women and in 21 men. Moreover, serum levels of FSH, LH, prolactin, estradiol, progesterone, and testosterone, sex hormone binding globulin, glucose, and insulin were measured. RESULTS: The circulating levels of total adiponectin and its multimers were not affected by the normal variation of estradiol and progesterone across the ovulatory menstrual cycle. In the whole number of participants, the total adiponectin and high molecular weight adiponectin levels were significantly different between genders and associated positively with age and sex hormone binding globulin levels, and negatively with testosterone and progesterone levels and the waist/hip ratio. In the multiple logistic regression analysis, after adjustment for age, gender, and sex hormone binding globulin and progesterone levels, significant predictors of total adiponectin levels were the waist/hip ratio and testosterone levels, and of high molecular weight adiponectin the testosterone levels. CONCLUSIONS: Normal menstrual cycle ovarian steroids are not involved directly in the regulation of secretion and/or metabolism of total adiponectin and its multimers. Testosterone seems to be responsible for the adiponectin's sexual dimorphism.