In childhood, the most common site of fracture is the distal forearm. To determine whether young girls with these fractures have low bone density more commonly than fracture-free controls, we measured bone density at the radius, spine, hip, and whole body and total body bone mineral content, lean tissue mass, and fat mass by dualenergy X-ray absorptiometry in 100 Caucasian girls aged 3-15 years with recent distal forearm fractures and 100 age-and gender-matched controls. Bone density (age-adjusted ratios of all cases:controls with 95% confidence intervals) was lower in cases at the ultradistal radius 0.

Receiver operating characteristic (ROC) curves were constructed to assess the value of body mass index (BMI) as a screening measure for total adiposity and to examine waist-to-hip ratio (WHR) and waist circumference as measures of central fat distribution. Body fat reference measurements were determined by dual-energy X-ray absorptiometry (DXA). The study population comprised 96 healthy white women aged 16-80 y. A positive reference test was defined as a result at or above the 75th percentile for our study population for all DXA measurements. Sensitivity and specificity were calculated at several percentile cutoffs for BMI, WHR, and waist girth. The areas under the ROC curves were calculated to compare the relative ability of each anthropometric technique to correctly classify subjects according to the reference measurement for that technique. BMI (our 75th percentile = 27.3) performed well as a screening measure of total adiposity, correctly identifying 83% of subjects with a high body fat mass while misclassifying only eight subjects [four false-negatives (subjects with high fat mass who were in the low BMI category) and four false-positives (subjects with a low fat mass who were in the high BMI category)]. The screening performance of WHR (our 75th percentile = 0.81) was lower, accurately categorizing 58% of subjects while misclassifying 28 subjects. By contrast, waist circumference (our 75th percentile = 86.9 cm) was significantly better than WHR at screening for regional fat distribution, accurately classifying 83% of subjects and misclassifying eight subjects (P < 0.05). We conclude that BMI and waist circumference provide simple yet sensitive methods for the estimation of total and central adiposity in groups of adult women.

Testicular development is governed by the combined influence of hormones and proteins, including FSH, inhibins, activins and follistatin (FST). This study documents the expression of these proteins and their corresponding mRNAs, in testes and serum from mice aged 0 through 91 days post partum (dpp), using real-time PCR, in situ hybridisation, immunohistochemistry, ELISA and RIA. Serum immunoactive total inhibin and FSH levels were negatively correlated during development, with FSH levels rising and inhibin levels falling. Activin A production changed significantly during development, with subunit mRNA and protein levels declining rapidly after 4 dpp, while simultaneously levels of the activin antagonists, FST and inhibin/activin b C , increased. Inhibin/activin b A and b B subunit mRNAs were detected in Sertoli, germ and Leydig cells throughout testis development, with the b A subunit also detected in peritubular myoid cells. The a, b A , b B and b C subunit proteins were detected in Sertoli and Leydig cells of developing and adult mouse testes. While b A and b B subunit proteins were observed in spermatogonia and spermatocytes in immature testes, b C was localised to leptotene and zygotene spermatocytes in immature and adult testes. Nuclear b A subunit protein was observed in primary spermatocytes and nuclear b C subunit in gonocytes and round spermatids. The changing spatial and temporal distributions of inhibins and activins indicate that their modulated synthesis and action are important during onset of murine spermatogenesis. This study provides a foundation for evaluation of these proteins in mice with disturbed testicular development, enabling their role in normal and perturbed spermatogenesis to be more fully understood.

To determine whether gender differences in body fat could be detected in prepubertal children using dual energy X-ray absorptiometry (DEXA), body composition was measured in 20 healthy boys aged 3±8 y matched for age, height and weight with 20 healthy girls. Although boys and girls did not differ in age, height, weight, body mass index (BMI) or bone mineral content, the boys had a lower percentage of body fat (13.5 AE 5.1 vs 20.4 AE 6.1%, P`0.01), a lower fat mass (3.2 AE 2.0 vs 4.9 AE 3.1 kg, P`0.01), and a higher bone-free lean tissue mass (18.6 AE 4.3 vs 17.0 AE 3.5 kg, P`0.01) than the girls. Girls had approximately 50% more body fat than the boys. This is the ®rst DEXA study to show that boys aged 3±8 y have less body fat than girls of similar age, height and weight. Thus, this technology demonstrates that signi®cant gender differences in body composition are evident, well before the onset of puberty.

Activin A is a potent growth and differentiation factor whose synthesis and bioactivity are tightly regulated. Both follistatin binding and inhibin subunit heterodimerization block access to the activin receptor and/or receptor activation. We postulated that the activin-␤ C subunit provides another mechanism regulating activin bioactivity. To test our hypothesis, we examined the biological effects of activin C and produced mice that overexpress activin-␤ C . Activin C reduced activin A bioactivity in vitro; in LNCaP cells, activin C abrogated both activin A-induced Smad signaling and growth inhibition, and in L␤T2 cells, activin C antagonized activin A-mediated activity of an follicle-stimulating hormone-␤ promoter. Transgenic mice that overexpress activin-␤C exhibited disease in testis, liver, and prostate. Male infertility was caused by both reduced sperm production and impaired sperm motility. The livers of the transgenic mice were enlarged because of an imbalance between hepatocyte proliferation and apoptosis. Transgenic prostates showed evidence of hypertrophy and epithelial cell hyperplasia. Additionally, there was decreased evidence of nuclear Smad-2 localization in the testis, liver, and prostate, indicating that overexpression of activin-␤ C antagonized Smad signaling in vivo. Underlying the significance of these findings, human testis, liver, and prostate cancers expressed increased activin-␤C immunoreactivity. This study provides evidence that activin-␤ C is an antagonist of activin A and supplies an impetus to examine its role in development and disease.