Influence of sports participation and menarche on bone mineral density of female high school athletes

Weight-bearing exercise during adolescence may enhance peak bone mineral density (BMD) and reduce osteoporosis risk. The association of sports participation before and after menarche with areal BMD (by central DXA) was investigated in 99 female high school athletes (age 15.5+/-1.3 year). The frequency and duration of structured sports (school-based or other organized team) were assessed using an interviewer-assisted questionnaire. Overall, the average number of years of weight-bearing sport participation was 7.4+/-3.4 years; 72% of the athletes began sport participation before menarche. Training patterns and BMD were examined by tertiles of yearly weight-bearing sport participation (hours/year) before (WBpre), after (WBpost) menarche, and in total (WBtotal). After adjusting for chronological age, gynecological age, and BMI, compared to athletes in the WBtotal low tertile, athletes in the WBtotal high tertile had significantly greater BMD at the spine (p=0.009), total hip (p=0.03), trochanter (p=0.03), and total body (p=0.009). Similar patterns were found by WBpre or WBpost status, separately, with the exception of spine BMD which was significantly different across tertiles in WBpost only (p<0.01). While the number of years of participation was similar across tertiles of WBtotal, the number of months/year was significantly greater among athletes in the high tertile than athletes in the low tertile (9.2+/-3.4 month/year versus 5.0+/-2.9 month/year, respectively (p<0.001)). These results indicate that near year-round participation in structured weight-bearing sports during early adolescence may help young girls optimize bone mineral accrual during these critical years, and may decrease their risk of osteoporosis with advancing age.     

Salivary leptin induces increased expression of growth factors in oral keratinocytes

We investigated the influence of salivary leptin, purified by affinity chromatography, on the proliferation of human oral keratinocytes. Furthermore we determined the time- and dose-dependency of the incubation with salivary leptin on the production of epidermal growth factor (EGF) and keratinocyte growth factor (KGF), which are growth factors relevant to keratinocyte proliferation. The analysis was performed both intra- and extracellularly. The relationship between the three cytokines in cell proliferation was studied by successive blocking with specific antibodies. The incubation of oral keratinocytes with recombinant and native leptin led to a significantly increased, dose-dependent cell proliferation (P<0.001). A further significant increase in proliferation was observed after incubating the cells with sterile filtered saliva (P<0.001). The increase in proliferation could not be observed by simultaneous incubation with salivary leptin and specific antibodies against either leptin or KGF (P<0.001). We found a significant dose-dependency between leptin incubation and production of KGF and EGF at the RNA and protein level. Both cytokines were expressed intracellularly and released into the culture medium, where they could be quantified by ELISA. Furthermore, there was a dose- and time-dependent increase in the phosphorylation of STAT-1 and STAT-3, indicating that Ob-R(b) (the long form of the leptin receptor) expressed by the keratinocytes is functional. It is conceivable that the leptin-induced proliferation in keratinocytes is mediated by this signalling pathway. This is the first study to show a physiological role of salivary leptin as a growth factor for keratinocyte proliferation in the oral cavity. We could demonstrate its influence on the production of other growth factors essential for this proliferative effect. Based on the findings of our study we assume an important role for salivary leptin in wound healing within the vulnerable oral cavity.     

Lipids, lipoproteins, and sexual maturation during adolescence: the Princeton maturation study.

This study encompassed a cross-sectional and longitudinal examination of schoolchildren as they entered into and passed through puberty, examining interrelationships between lipids, lipoproteins, and sexual maturation. In the first year of the study (1976), 529 schoolchildren in grades 5–12 participated; 203 were restudied in 1977, and 141 in 1978. At each yearly visit, the children's stage of sexual maturation was assessed using the Tanner scale. Plasma cholesterol and triglyceride were quantitated each year; high, low, and very low density lipoprotein cholesterol (C-HDL, C-LDL, C-VLDL) levels were measured in the second and third years of the study. In males, cross-sectional decrements in plasma cholesterol were observed with increasing sexual maturation (Tanner stages 1–4), with an increment at Tanner 5 (sexual maturity); plasma triglyceride levels rose at all stages save Tanner 4. The mid-Tanner fall in plasma cholesterol appears (longitudinally) to be accounted for by reduction in C-HDL, while the rise in plasma cholesterol at Tanner 5 may be produced by an increase in C-LDL. Changes in age and Quetelet indices did not appear to relate closely to changes in C-VLDL in 12- and 13-yr-old males, but increasing age and Quetelet indices in 14–15-yr old males accompanied increasing C-VLDL. Cross-sectional studies in females revealed that plasma cholesterol fell at Tanner stages 3 and 4 and rose at stage 5; plasma triglyceride rose during all stages except Tanner 4. Longitudinal studies suggested that the decrements in plasma cholesterol in females may be partially accounted for by reductions in C-HDL; the increase in plasma cholesterol in late sexual development may be accounted for by an increase in C-LDL. In male children, we speculate that the fall in C-HDL and late rise in C-LDL as sexual maturation progresses is associated with increased testosterone production.     

Quantitative estimations of the contribution of different bile acid pathways to total bile acid synthesis in the rat

BACKGROUND & AIMS: Cholesterol degradation to bile acids occurs via "classic" or "alternative" bile acid biosynthetic pathways. The aim of this study was to assess the contributions of these two pathways to total bile acid synthesis in vivo. METHODS: Rats with biliary fistulas were infused with squalestatin for 24 and 48 hours; specific activities of cholesterol 7 alpha-hydroxylase (C7 alpha H) and sterol 27- hydroxylase (S27H) and rates of bile acid synthesis were determined. RESULTS: Continuous squalestatin infusion (15 micrograms/h) decreased C7 alpha H specific activities to 4% and 12% of paired biliary fistula controls at 24 and 48 hours, respectively (P < 0.05) without any changes in S27H specific activities (82% and 95% of controls). At 24 hours, bile acid synthesis decreased to 43% (P < 0.05) but returned to 87% at 48 hours (P = NS). Cholic acid synthesis decreased at 24 hours but returned to control levels at 48 hours. Similar changes in C7 alpha H, S27H, and bile acid synthesis were observed in primary rat hepatocytes after addition of squalestatin (1.0 mumol/L). CONCLUSIONS: In the face of persistent suppression of C7 alpha H and the classic pathway, an alternative pathway becomes a main pathway of bile acid synthesis capable of generating cholic and chenodeoxycholic acids. The observed induction of bile acid synthesis via an alternative pathway or pathways represents an important mechanism for maintenance of cholesterol homeostasis in the rat. (Gastroenterology 1997 Dec;113(6):1949-57)     

7 alpha-dehydroxylating bacteria enhance deoxycholic acid input and cholesterol saturation of bile in patients with gallstones

BACKGROUND & AIMS: Excessive deoxycholic acid (DCA) in the bile acid pool with cholesterol supersaturation of bile is prevalent in patients with cholesterol gallstones (CGs). This study examined whether this is caused by enhanced conversion of cholic acid (CA) to DCA by intestinal bacteria. METHODS: Ten patients with CGs with DCA excess (DCA/CA pool ratio, > 1.5) and 10 patients with low DCA (ratio, < 1.0) were compared for CA and DCA kinetics, ileal absorption of 75-Se-homotaurocholic acid (75-SeHCAT), and CA-7 alpha-dehydroxylation activity of the fecal microflora; the effects of ampicillin treatment on DCA excess were studied in 7 patients. RESULTS: Patients with DCA excess and low DCA differed (P < 0.01) in the pool size of CA (mean, 5.8 vs. 34) and DCA (28 vs. 11 mumol/kg) and DCA input (8.8 vs. 3.5 mumol.kg-1.day-1. Whereas 75-SeHCAT excretion was similar, CA-7 alpha-dehydroxylation activity and levels of fecal 7 alpha-dehydroxylation bacteria were 3- fold and 1000-fold higher (P < 0.01) in patients with DCA excess, respectively. Ampicillin treatment decreased (P < 0.02) CA-7 alpha- dehydroxylation activity and DCA pool size, expanded the CA pool to normal size, and lowered cholesterol saturation of bile. CONCLUSIONS: Increased CA-7 alpha-dehydroxylation activity of the intestinal microflora may be an important factor for CG formation or growth in these patients. (Gastroenterology 1996 Dec;111(6):1611-20)