Sex Hormones, Gonadotropins, and Sex Hormone-binding Globulin in Infants Fed Breast Milk, Cow Milk Formula, or Soy Formula.

Measurement of endogenous hormones in early life is important to investigate the effects of hormonally active environmental compounds. To assess the possible hormonal effects of different feeding regimens in different sample matrices of infants, 166 infants were enrolled from two U.S hospitals between 2006 and 2009. The children were classified into exclusive soy formula, cow milk formula or breast milk regimens. Urine, saliva and blood samples were collected over the first 12 months of life. Estradiol, estrone, testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) levels were measured in the three matrices. Lower estradiol and LH levels were found in urine and saliva samples of soy formula-fed boys compared to cow formula-fed boys. Higher LH level was found in urine samples of soy formula-fed girls compared to cow formula-fed girls. However, we found neither a neonatal testosterone rise in the boys nor a gender-specific difference in testosterone levels, which suggests that urinary testosterone levels may not accurately reflect blood levels during mini-puberty. Nevertheless, our study shows that blood, urine and saliva samples are readily collectible and suitable for multi-hormone analyses in children and allow examination of hypotheses concerning endocrine effects from dietary compounds.

The uridine diphosphate glucuronosyltransferase 2B15 D85Y and 2B17 deletion polymorphisms predict the glucuronidation pattern of androgens and fat mass in men.

CONTEXT: Previous in vitro studies have demonstrated that the UDP glucuronosyltransferase (UGT)2B15 and UGT2B17 glucuronidate androgens and their metabolites. OBJECTIVE: Our objective was to determine in vivo whether the UGT2B15 D85Y and the UGT2B17 deletion polymorphisms predict androgen glucuronidation and body composition. PARTICIPANTS: Two population-based cohorts including young adult (n = 1068; age = 18.9 yr) and elderly (n = 1001; age = 75.3 yr) men were included in the study. MAIN OUTCOME MEASURES: Serum and urine levels of testosterone (T) and dihydrotestosterone (DHT) were measured by gas chromatography-mass spectrometry, and serum levels of the major glucuronidated androgen metabolites androstane-3alpha,17beta-diol(androstanediol)-3-glucuronide, androstanediol-17-glucuronide, and androsterone-glucuronide were measured by liquid chromatography-tandem mass spectrometry. Body composition was measured by dual-energy x-ray absorptiometry. RESULTS: Both the UGT2B15 D85Y and the UGT2B17 deletion polymorphisms were associated with serum levels of androstanediol-17-glucuronide (P < 0.001) but not with levels of androstanediol-3-glucuronide or androsterone-glucuronide in both cohorts. Glucuronidation of T and DHT was associated with the UGT2B17 deletion but not with the UGT2B15 D85Y polymorphism, suggested by strong associations between the deletion polymorphism and urine levels of these two hormones. Both polymorphisms were associated with several different measures of fat mass (P < 0.01). The UGT2B17 deletion polymorphism was associated with insulin sensitivity (P < 0.05) as indicated by the homeostasis model assessment index. CONCLUSIONS: The UGT2B15 D85Y and the UGT2B17 deletion polymorphisms are both predictors of the glucuronidation pattern of androgens/androgen metabolites. Our findings indicate that UGT2B17 is involved in 17-glucuronidation of mainly T but also of DHT and androstanediol and that UGT2B15 is involved in the 17-glucuronidation of androstanediol. Furthermore, these two polymorphisms are predictors of fat mass in men.

Determinants of bone density in healthy older men with low testosterone levels.

BACKGROUND: Osteoporosis is a significant problem in older men, 30% of all hip fractures occur in men and the mortality rate following hip fracture exceeds that of women. Testosterone is thought to be important in the development of peak bone mass hut its role in age-related bone loss is not established. The purpose of this study was to define the predictors of bone mass ill healthy older men with low testosterone levels but without symptomatic osteoporosis. METHODS: Eighty-three community-dwelling white men, aged more than 65 years old, selected for low bioavailable testosterone levels (< or = 4.44 nmol/l) participated in a cross-sectional study located at a university general clinical research center. Sex hormone concentrations and markers of bone turnover were assayed in serum and urine. Risk factors for osteoporosis and physical activity were ascertained by physical examination and questionnaire, including the Physical Activity Scale in the Elderly (PASE) questionnaire. Bone mineral densities of the femoral neck (FN BMD), spine, and whole body were measured by dual x-ray absorptiometry. Lower extremity muscle strength (1 repetition maximum) was measured using a leg press machine. RESULTS: Mean bone mineral density values were 0.93 +/- 0.14 g/cm2 for femoral neck, 1.31 +/- 0.23 g/cm2 for spine, and 1.22 +/- 0.12 g/cm2 for whole body. Thirty-one of the 82 subjects (37%) had t scores < -1 and 12 of 82 subjects (15%) had t scores < -2.5 at the femoral neck. Multiple linear regression analysis demonstrated that bioavailable testosterone, body mass index (BMI), and PASE scores were positively correlated with, and significant predictors of, femoral neck BMD, accounting for 34.4% of the variance in FN BMD (F = 10.10, p = .001). Examining each variable independently, bioavailable testosterone accounted for 20.7%, physical activity score for 9.0%, and BMI for 6.5% of FN BMD. Using analysis of variance, mean values for FN BMD were significantly different between men grouped by tertile of bioavailable testosterone (F = 6.192, p = .003). FN BMD mean values were 0.86 +/- 0.14 g/cm2 for the lowest tertile, 0.94 +/- 0.16 for the middle tertile, and 0.99 +/- 0.14 for the highest tertile. Markers of bone turnover were inversely correlated, and strength directly correlated with BMD, but did not contribute to the multiple regression model. CONCLUSIONS: Fifty-two percent of older men with low bioavailable testosterone levels had BMD levels below the young adult normal range and are likely at an increased risk of fracture. Bioavailable testosterone, BMI, and physical activity scores were significant determinants of FN BMD in these men. These variables are potentially modifiable and, therefore, amenable to intervention. Hence, our results suggest the need for testosterone replacement and physical activity intervention trials in men at risk for osteoporotic fractures.

Human sex hormone-binding globulin gene expression in transgenic mice.

The sex hormone-binding globulin gene (shbg) is expressed in the liver and testis as well as in several other tissues that play important roles in reproduction. Expression of shbg in the human liver results in the production of plasma sex hormone-binding globulin (SHBG), which regulates the bioavailability of sex steroids in the blood. Although shbg is not expressed in rodent livers postnatally, it gives rise to the androgen-binding protein in their testes upon sexual maturation. Human shbg is also expressed in the testis, but its products and their function are less well characterized. To study the expression of human shbg in different tissues and the consequences of overexpressing this gene in vivo, we have produced several lines of mice containing approximately 11-kilobase (kb; shbg11) or 4.3-kb (shbg4) human shbg genomic fragments that comprise all eight exons encoding SHBG as well as approximately 6 kb or approximately 0.9 kb of 5'-flanking DNA, respectively. Northern blots indicated that human shbg transcripts were most abundant in liver, kidney, and testis of the shbg11 mice. The 4.3-kb shbg transgenes were expressed at similar levels in liver and kidney, but the abundance of human shbg transcripts in their testes was much lower than that in shbg11 mice. Primer extension analysis indicated that transcription starts 60 bp from the translation initiation codon for SHBG in liver and kidney of shbg11 mice, and that the shbg transcripts in their testis are derived from a separate promoter flanking an alternative exon that replaces the exon containing the translation initiation codon for SHBG or androgen-binding protein. At the cellular level, the human shbg transgenes are expressed in clusters of hepatocytes located mainly within the periportal region of hepatic lobules and in the epithelial cells lining the proximal convoluted tubules of the kidney. This results in high levels of human SHBG in serum (1.45-1.72 nmol/ml) and urine (6-16 pmol/ml) of mature male shbg mice. The abundance and distribution of human shbg transcripts in the Sertoli cells of shbg11 mice vary throughout the spermatogenic cycle, with levels increasing in the Sertoli cell cytoplasm until stage VII of spermatogenesis and declining after stage IX. At stages X-XII of spermatogenesis, these transcripts concentrate at the adluminal compartment of the Sertoli cells, and this suggests that they have a role in the elongation phase of spermiogenesis. The presence of human SHBG in the blood of shbg transgenic mice may result in serum levels of testosterone that are 10-100 times higher than those in wild-type littermates. Despite this, their reproductive performance is normal, and there is no obvious phenotypic abnormalities even in animals homozygous for the transgenes.

Urine excretion of androgen hormones in professional racing cyclists.

This study was performed on 16 professional racing cyclists to examine changes in urine concentrations of androgen hormones (testosterone, epitestosterone, androsterone, etiocholanolone, 11-hydroxy-androsterone and 11-hydroxy-etiocholanolone) and plasma sex hormone binding globulin (SHBG) after training and after competition. The urinary concentrations of androgen hormones decreased during the period of training and increased during competition, this being the reverse of what happened to SHBG plasma concentrations. These changes would suggest that physical activity may have an influence on the elimination of androgen hormones and on the synthesis of its transporting protein SHBG.