We hypothesize that alterations in growth, 4 compartment of body composition (BC), regional distribution of body fat (RDBF; via MRI, anthropometry), and bone mineralization (BM; via DEXA) in boys and girls are driven by alterations in GH and gonadal and adrenal steroid hormone levels, and are modified by energy and nutrient intake (nonconsecutive, 7 day, 24 hr diet recall), energy expenditure (EE; via doubly labeled water, indirect calorimetry, 7 day physical activity recall) and physical fitness (via V02 peak), which act on the genetic background. A better understanding of the factors that control the pubertal changes in BC, RDBF and BM can lay the ground work for the comprehension, prevention and treatment of various disease processes including non insulin-dependent diabetes mellitus (NIDDM), cardiovascular diseases (CVD) and osteopenia, whose antecedents likely occur during childhood and adolescence. However, valid and precise data for BC, RDBF, and BM and the factors controlling them are lacking for children and adolescents. Girls with the Turner Syndrome (n=8) receiving GH for at least one year, prior to estrogen replacement, and boys with constitutional delay of growth (n=8) not on androgen therapy will serve as models for adolescent growth in the presence of adequate GH, but physiologically deficient sex hormones. Girts with precocious puberty (n=8) on GnRH analogue therapy for at least one year provide a model for pubertal growth, with accompanying high levels of GH and gonadal steroids, at an inappropriately early age. Control data will be provided by a cohort of 44 normally growing children at all stages of puberty followed in a parallel protocol. With these clinical models of hormonal influence and normal controls we shall determine the hormonal and nutritional mechanisms that stimulate growth and induce the alterations in BC, RDBF and BM in boys and girls at puberty. This model will also provide insights into the role of hormonal and nutritional factors in progressive diseases (CVD, NIDDM, osteopenia). Both the boys and girls with clinical growth disorders and the controls will be entered as staggered, mixed longitudinal groups. Specific hypotheses to be tested include: 1) somatic growth and maturation will be directly related to GH, IGF-1 and gonadal and adrenal steroid levels; 2) % body fat (%BF) and visceral fat will be directly related to energy and fat intake and inversely related to EE and pre- and late-pubertal GH secretion; 3) gender differences in RDBF will be related to changes in gonadal steroid levels; 4) despite increases in GH secretion during puberty, % BF and visceral fat will increase due to the over-riding effects of gonadal steroids; 5) BM will be directly related to physical activity, calcium intake, gonadal steroids and GH secretion; and 6) EE, energy and nutrient intake, and physical fitness will modulate hormonal influences on BC, RDBF, and BM. Interactions to be tested include: 1) increased aerobic fitness will increase GH secretion and reduce %BF and visceral fat but, dietary fat intake will reduce GH secretion causing an increase in % BF and visceral fat; 2) physical activity will increase BM, but inadequate energy and calcium intake and/or excessive activity will reduce gonadal steroids and reduce BM.
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