Biomedical subjects

Pamela A Clark

Publications and source records attributed to Pamela A Clark.

4 recordsLinked to original sources

PubMed2005

Pubertal alterations in growth and body composition: IX. Altered spontaneous secretion and metabolic clearance of growth hormone in overweight youth.

Deconvolution analysis was used to determine 12-hour spontaneous nocturnal growth hormone (GH) secretion and GH half-life in lean (body mass index, <85th percentile; n = 39) and overweight (body mass index, > or =85th percentile; n = 18) youth. The integrated GH concentration, GH burst mass, and half-life were lower (P < .05) in overweight than in lean youth. For each unit increase in percentage of body fat, integrated serum GH concentrations, secretory burst mass, and half-life declined by 83.6 microg/L per minute (r = -0.39, P < .01), 0.22 microg/L (r = -0.28, P < .05), and 0.2 minute (r = -0.38, P < .01), respectively. The effect of overweight on GH secretion was independent of pubertal status. Hierarchical regression models tested the hypothesis that altered GH secretion in youth is more related to total adiposity than abdominal visceral fat. When age, sex, fat-free mass, testosterone, and estradiol were held constant, the sequential addition of abdominal visceral fat did not increase R2 for any GH secretion variable. Sequential addition of percentage of body fat increased R2 (P < .05) for integrated GH concentration, total secretory rate, secretory burst mass, and pulsatile production rate. We conclude that serum GH concentrations are reduced in overweight youth primarily because of reduced GH burst mass with no change in the number of secretory events and secondarily to reduced GH half-life. Based on the model that GH-releasing hormone predominantly increases GH pulse amplitude whereas somatostatin primarily controls GH pulse frequency, these results suggest that overweight in youth diminishes GH-releasing hormone stimulation resulting in truncated GH bursts but does not alter the number of somatostatin withdrawal intervals so that GH burst frequency is conserved.

Abdomen↗

PubMed2003

Relationship of leptin to bone mineralization in children and adolescents.

Serum leptin concentrations and bone mass are concordant in several respects. Obesity is associated with increased serum leptin concentrations and bone mineral, whereas undernutrition reduces serum leptin concentrations and bone mineral. Furthermore, both bone mineral and serum leptin concentrations increase at the initiation of puberty. However, there is a lack of empirical evidence of an independent association of serum leptin concentrations and bone mineral in youth. Thus, we used hierarchical regression to determine whether serum leptin concentrations were related to bone mineral in boys (n = 28) and girls (n = 31). Bone mineral content, density, and apparent density of the total body and body regions were measured by dual-energy x-ray absorptiometry and statistically adjusted for chronological age, fat mass, bone-free fat-free mass, and serum IGF-I and estradiol concentrations. Sequential addition of serum log((10)) leptin concentrations to the block of body size variables and the block of hormone variables did not increase R(2) for any of the total or regional bone mineral content, bone mineral density, and bone mineral apparent density variables. We conclude that serum leptin concentrations do not add to the prediction of bone mineral in youth after accounting for age, fat mass, bone-free fat-free mass, and serum IGF-I and estradiol concentrations.

Adipose Tissue↗

PubMed2002

Growth at puberty.

Somatic growth and maturation are influenced by a number of factors that act independently or in concert to modify an individual's genetic potential. The secular trend in height and adolescent development is further evidence for the significant influence of environmental factors on an individual's genetic potential for linear growth. Nutrition, including energy and specific nutrient intake, is a major determinant of growth. Paramount to normal growth is the general health and well-being of an individual; in fact, normal growth is a strong testament to the overall good health of a child. More recently the effect of physical activity and fitness on linear growth, especially among teenage athletes, has become a topic of interest. Puberty is a dynamic period of development marked by rapid changes in body size, shape, and composition, all of which are sexually dimorphic. One of the hallmarks of puberty is the adolescent growth spurt. Body compositional changes, including the regional distribution of body fat, are especially large during the pubertal transition and markedly sexually dimorphic. The hormonal regulation of the growth spurt and the alterations in body composition depend on the release of the gonadotropins, leptin, the sex-steroids, and growth hormone. It is very likely that interactions among these hormonal axes are more important than their main effects, and that alterations in body composition and the regional distribution of body fat actually are signals to alter the neuroendocrine and peripheral hormone axes. These processes are merely magnified during pubertal development but likely are pivotal all along the way from fetal growth to the aging process.

Adipose Tissue↗

PubMed2002

A novel mutation in helix 12 of the vitamin D receptor impairs coactivator interaction and causes hereditary 1,25-dihydroxyvitamin D-resistant rickets without alopecia.

Hereditary vitamin D-resistant rickets (HVDRR) is a genetic disorder most often caused by mutations in the vitamin D receptor (VDR). The patient in this study exhibited the typical clinical features of HVDRR with early onset rickets, hypocalcemia, secondary hyperparathyroidism, and elevated serum concentrations of alkaline phosphatase and 1,25-dihydroxyvitamin D [1,25-(OH)(2)D(3)]. The patient did not have alopecia. Assays of the VDR showed a normal high affinity low capacity binding site for [(3)H]1,25-(OH)(2)D(3) in extracts from the patient's fibroblasts. However, the cells were resistant to 1,25-dihydroxyvitamin D action as demonstrated by the failure of the patient's cultured fibroblasts to induce the 24-hydroxylase gene when treated with either high doses of 1,25-(OH)(2)D(3) or vitamin D analogs. A novel point mutation was identified in helix H12 in the ligand-binding domain of the VDR that changed a highly conserved glutamic acid at amino acid 420 to lysine (E420K). The patient was homozygous for the mutation. The E420K mutant receptor recreated by site-directed mutagenesis exhibited many normal properties including ligand binding, heterodimerization with the retinoid X receptor, and binding to vitamin D response elements. However, the mutant VDR was unable to elicit 1,25-(OH)(2)D(3)-dependent transactivation. Subsequent studies demonstrated that the mutant VDR had a marked impairment in binding steroid receptor coactivator 1 (SRC-1) and DRIP205, a subunit of the vitamin D receptor-interacting protein (DRIP) coactivator complex. Taken together, our data indicate that the mutation in helix H12 alters the coactivator binding site preventing coactivator binding and transactivation. In conclusion, we have identified the first case of a naturally occurring mutation in the VDR (E420K) that disrupts coactivator binding to the VDR and causes HVDRR.

Alopecia↗