| Budget Amount *help |
¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1990: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1989: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
The roles of the hypothalamus and pituitary in somatic growth and development from the perinatal period to puberty were examined. The ontogenic studies of hypothalamic hormones in rats revealed that neuropeptide Y (NPY) appeared in the arcuate nuclei early at the 14.5th day of gestation, both somatostatin (SRIF) and proopiomelanocortin (POMC) were detected on the next day, and then growth hormone-releasing factor (GRF), luteinizing hormone-releasing hormone (LHRH) and dopamine were finally seen. NPY containing-neurons form many synapses with SRIF-neurons,LHRH-neurons and other hypothalamic neurons. Inaddition, NPY molecules were abundant at the early phase of ontogeny but gradually decreased in the latter phase. These results suggest that NPY may possess an important role in normal development of the hypothalamus. We also demonstrated that messenger (m) RNA of basic fibroblast growth factor (bFGF) were present in the hypothalamus as well as the hippocampus and brain stem by the norther
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n blot analysis. Relationship between NPY-neurons and bFGF mRNA remains to be investigated. Besides. both bFGF and acidic fibroblast growth factor (aFGF) increascd the mRNA levels, synthesis and contents of prolactin (PRL) in GH_3 cells, but not of growth hormone (GH). Neither bFGF nor aFGF affected the cell growth, assessed by thymidine incorporation and DNA contents. Using a monolayer culture system of rat anterior pituitary, we observed that insulin-like growth factor (IGF) -I and -II stimulated of LH and FSH as well as TSH, suggesting a physiological role of IGF-I and -II in pubertal development. On the other hand, GH plays a principal role in normal somatic growth. Although hypothalamic GRF is absolutely necessary for GH gene expression in the pituitary, our studies revealed that SRIF unexpectedly possesses a permissive action for stimulating GH gene expression in collaboration with GRF. Various stimuli could influence somatic growth ; for instance, chronic stress like immobilization causes severe retardation of skeletal growth with pubertal development, and malnutrition also induces growth failure.Under these circumstances, pituitary GH mRNA levels were markedly decreased, the amounts of secreted GH diminished and serum IGF-I levels were exclusively low. The plausible changes in the hypothalamus are expected in these conditions, but the precise mechanisms remain unclarified. Less
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