Campos-Barros A, Meinhold H, Stula M, Müller F, Köhler R, Eravci M, Putzien O, Baumgartner A
Psychiatrische Klinik and Poliklinik (Universitätsklinikum Rudolf-Virchow, Berlin, Germany.
J Pharmacol Exp Ther. 1994 Mar;268(3):1143-52.
The effect of the antidepressant desipramine (DMI) on the activities of the three iodothyronine deiodinase isoenzymes involved in the central metabolism of thyroid hormones were investigated in 11 brain regions and 3 peripheral tissues in the rat. The investigations were carried out at three different times during the light/dark cycle: 5 A.M., 1 P.M. and 11 P.M. Interest is focused on changes in the two enzymes that catalyze: i) the 5'deiodination of T4 to the biologically active T3, i.e., type II 5'deiodinase (5'D-II), and ii) the 5 (or inner-ring) deiodination of T3 to the biologically inactive 3,3'T2, i.e., type III 5 deiodinase (5D-III). Fourteen days' treatment with 20 mg/kg DMI, but not with 5 mg/kg DMI, induced significant increases in 5'D-II in eight different areas of the CNS. The regions affected were identical to those that receive noradrenergic input from the locus coeruleus. Even control animals showed a circadian rhythm of 5'D-II activity in some brain regions, and the effects of DMI also depended on the time of death within the 24-hr rhythm. 5D-III was not affected. Serum T4 were lower after administration of DMI, most probably because of enhanced tissue uptake of T4. This is in line with the corresponding finding in depressed patients, indicating that similar changes in both central and peripheral thyroid hormone metabolism may occur after antidepressant pharmacotherapy in both humans and rats. These data support the hypothesis that interactions with the CNS metabolism of the thyroid hormones may be involved in the mechanisms of action of DMI.
在大鼠的11个脑区和3个外周组织中，研究了抗抑郁药地昔帕明（DMI）对参与甲状腺激素中枢代谢的三种碘甲状腺原氨酸脱碘酶同工酶活性的影响。研究在光/暗周期的三个不同时间进行：上午5点、下午1点和晚上11点。研究重点是催化以下反应的两种酶的变化：i）将T4 5'脱碘生成生物活性T3，即II型5'脱碘酶（5'D-II）；ii）将T3进行5（或内环）脱碘生成生物无活性的3,3'T2，即III型5脱碘酶（5D-III）。用20mg/kg DMI治疗14天，但5mg/kg DMI未产生此效果，可使中枢神经系统八个不同区域的5'D-II显著增加。受影响的区域与那些接受来自蓝斑去甲肾上腺素能输入的区域相同。即使是对照动物，某些脑区的5'D-II活性也表现出昼夜节律，DMI的作用也取决于24小时节律内的死亡时间。5D-III未受影响。给予DMI后血清T4降低，很可能是由于T4的组织摄取增加。这与抑郁症患者的相应发现一致，表明在人类和大鼠中，抗抑郁药物治疗后中枢和外周甲状腺激素代谢可能会发生类似变化。这些数据支持了一种假说，即与甲状腺激素中枢代谢的相互作用可能参与了DMI的作用机制。
