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外源性甲状腺素和地塞米松对肝脏铜蓝蛋白mRNA及血清活性的发育调控

Developmental regulation of hepatic ceruloplasmin mRNA and serum activity by exogenous thyroxine and dexamethasone.

作者信息

Fitch C A, Song Y, Levenson C W

机构信息

Department of Nutrition, Food, and Exercise Sciences, Florida State University, Tallahassee, Florida 32306-4340, USA.

出版信息

Proc Soc Exp Biol Med. 1999 May;221(1):27-31. doi: 10.1046/j.1525-1373.1999.d01-50.x.

DOI:10.1046/j.1525-1373.1999.d01-50.x
PMID:10320628
Abstract

Ceruloplasmin (Cp) is a copper-dependent oxidase with roles that include the regulation of iron metabolism, participation in the acute-phase response to inflammation, and antioxidant systems. Although developmental increases in hepatic Cp gene expression and serum activity have been described, the molecular mechanisms that are responsible for this regulation are not fully understood. The studies described here explored the possible role of glucocorticoids and thyroxine (T4) in the early neonatal development of Cp by the administration of these hormones on postnatal Day 1 (24 hr after birth), and the measurement of both hepatic Cp mRNA and serum activity through postnatal Day 10. Administration of the synthetic glucocorticoid hormone, dexamethasone (2 micrograms/g body wt), resulted in an increase in Cp mRNA on Days 3-7 that was accompanied by an increase in serum Cp activity that reached statistical significance at Day 10. Exogenous T4 (2 micrograms/g body wt) significantly increased Cp mRNA 24 hr after administration. Serum Cp activity was also significantly elevated by the early neonatal administration of T4. Furthermore, gestational hypothyroidism resulted in a significant decrease in Cp activity after postnatal Day 3. These data suggest a role for thyroid hormone and possibly glucocorticoids in the normal developmental regulation of Cp.

摘要

铜蓝蛋白(Cp)是一种铜依赖性氧化酶,其作用包括调节铁代谢、参与炎症的急性期反应以及抗氧化系统。尽管已有研究描述了肝脏中Cp基因表达和血清活性在发育过程中的增加,但负责这种调节的分子机制尚未完全了解。本文所述的研究通过在出生后第1天(出生后24小时)给予糖皮质激素和甲状腺素(T4),并在出生后第10天测量肝脏Cp mRNA和血清活性,探讨了它们在Cp新生儿早期发育中的可能作用。给予合成糖皮质激素地塞米松(2微克/克体重)后,第3 - 7天Cp mRNA增加,同时血清Cp活性增加,在第10天达到统计学显著水平。外源性T4(2微克/克体重)给药后24小时,Cp mRNA显著增加。新生儿早期给予T4也显著提高了血清Cp活性。此外,妊娠期甲状腺功能减退导致出生后第3天以后Cp活性显著降低。这些数据表明甲状腺激素以及可能的糖皮质激素在Cp的正常发育调节中发挥作用。

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