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  • 學位論文

胎兒時期分泌之類固醇賀爾蒙對小鼠腎上腺及下視丘腦垂腺腎上腺軸生長發育的影響

Development of Hypothalamic-Pituitary-Adrenal Axis and Adrenal Requires Fetal Steroids Synthesis

指導教授 : 鍾邦柱 郭應誠

摘要


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並列摘要


During pregnancy, fetal corticosterone is derived both from that transferred from mother and that secreted from their own adrenal. The P450scc (Cyp11a1) enzyme, which catalyzes the first step of steroidogenesis, contributes to de novo synthesis of steroid hormones. Thus, the corticosterone in Cyp11a1 null embryos all comes from their mother through placenta, and this provides an animal model to study the disorder due to the lack of de novo synthesis of steroid hormones. The normal level of plasma corticosterone in the Cyp11a1 null mice indicates the transplacental corticosterone provides enough corticosterone level in fetal circulation. Even so, the developmental disorders were still detected. The null mice had enlarged and randomly distributed oil droplets in the adrenal at 16.5 dpc and the structure of adrenal was altered in parallel with random distribution of proliferating cells. The medulla migration was normal in the Cyp11a1 null mice, but this null adrenal could not synthesize epinephrine. In HPA axis of null mice, pituitary POMC had higher expression than the wildtype, which was consistent with the higher ACTH level in the plasma. Our results suggest that: (1) Inability of the fetal steroid synthesis during pregnancy affects adrenal organization. (2) The development of adrenal medulla required de novo corticosterone, which synthesize from vicinal cortex. (3) The de novo synthesis of steroid hormone is essential for normal development of the negative feedback function in HPA axis.

並列關鍵字

HPA axis Cyp11a1 corticosterone fetal development adrenal P450scc

參考文獻


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