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甲状腺激素对大鼠肝脏和心脏中β-肾上腺素能受体偶联腺苷酸环化酶的差异调节:皮质类固醇的可能作用。

Differential regulation of beta-adrenergic receptor-coupled adenylate cyclase by thyroid hormones in rat liver and heart: possible role of corticosteroids.

作者信息

Sundaresan P R, Banerjee S P

机构信息

Department of Pharmacology, University of Rochester, School of Medicine and Dentistry, N.Y.

出版信息

Horm Res. 1987;27(2):109-18. doi: 10.1159/000180796.

DOI:10.1159/000180796
PMID:2820855
Abstract

Thyroid hormone regulation of beta-adrenergic receptor-coupled adenylate cyclase activity was studied in rat liver and heart particulate fractions. Thyroidectomy (Tx) increased isoproterenol-stimulated cAMP accumulation in the liver and decreased it in the heart. Administration of L-thyroxine (L-T4) or L-3,3',5-triiodothyronine (L-T3) reversed these changes in both liver and heart. The changes observed in liver beta-receptor-coupled adenylate cyclase activity after Tx were similar to those reported after adrenalectomy (ADX). Thus the hypothesis was considered that these changes with altered thyroid status are produced indirectly through alteration in adrenal corticosteroids. Hydrocortisone in Tx rats decreased liver isoproterenol-stimulated adenylate cyclase activity but had no significant effect on the heart. Serum corticosterone levels were decreased significantly (by 34%) in Tx rats, as compared to euthyroid rats. Administration of L-T4 to Tx rats doubled the serum corticosterone levels. In Tx-ADX rats, L-T4 had no significant effect on liver beta-receptor-coupled adenylate cyclase. However, L-T4 significantly increased heart beta-receptor-coupled adenylate cyclase in these animals. Dexamethasone, but not deoxycorticosterone, decreased liver isoproterenol-stimulated cAMP accumulation in Tx animals to the same extent as was observed with L-T4 and hydrocortisone. Thus overall the results indicate that in the liver, as opposed to the heart, thyroid hormones regulate beta-adrenergic receptor-coupled adenylate cyclase indirectly through corticosteroids. Glucocorticoid rather than mineralocorticoid activity seems to be responsible for this regulation.

摘要

在大鼠肝脏和心脏微粒体部分研究了甲状腺激素对β-肾上腺素能受体偶联的腺苷酸环化酶活性的调节作用。甲状腺切除术(Tx)增加了异丙肾上腺素刺激的肝脏中cAMP的积累,而降低了心脏中的cAMP积累。给予L-甲状腺素(L-T4)或L-3,3',5-三碘甲状腺原氨酸(L-T3)可逆转肝脏和心脏中的这些变化。Tx后肝脏β受体偶联的腺苷酸环化酶活性的变化与肾上腺切除术(ADX)后报道的变化相似。因此,有人认为甲状腺状态改变引起的这些变化是通过肾上腺皮质类固醇的改变间接产生的。Tx大鼠中的氢化可的松降低了肝脏中异丙肾上腺素刺激的腺苷酸环化酶活性,但对心脏没有显著影响。与甲状腺功能正常的大鼠相比,Tx大鼠的血清皮质酮水平显著降低(降低34%)。给Tx大鼠给予L-T4可使血清皮质酮水平加倍。在Tx-ADX大鼠中,L-T4对肝脏β受体偶联的腺苷酸环化酶没有显著影响。然而,L-T4显著增加了这些动物心脏中β受体偶联的腺苷酸环化酶。地塞米松而非脱氧皮质酮,在Tx动物中降低肝脏异丙肾上腺素刺激的cAMP积累的程度与L-T4和氢化可的松相同。因此,总体结果表明,与心脏不同,在肝脏中甲状腺激素通过皮质类固醇间接调节β-肾上腺素能受体偶联的腺苷酸环化酶。这种调节似乎是由糖皮质激素而非盐皮质激素的活性负责。

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