Wasco Emily C, Martinez Elena, Grant Katherine S, St Germain Emily A, St Germain Donald L, Galton Valerie Anne
Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756-0001, USA.
Endocrinology. 2003 Oct;144(10):4253-61. doi: 10.1210/en.2003-0490. Epub 2003 Jul 10.
The deiodinase types 2 and 3 (D2, D3), which convert T4 to active and inactive metabolites, respectively, are expressed in the rodent uterus and highly induced during pregnancy. To examine the factors regulating the expression of these enzymes in this tissue, we studied D2 and D3 activity in pregnant rats, in pseudopregnant rats before and after the induction of artificial decidualization, and in ovariectomized rats treated with 17beta-estradiol (E2) and/or progesterone (P). Our results demonstrate that induction of D3 activity begins immediately after implantation and increases markedly over the next 72 h. A similar time course and magnitude of D3 induction is noted in the artificially decidualized uterus in pseudopregnant rats, whereas only minimal increases in activity are observed in the nondecidualized control uterine horns in the same animal. In contrast, D2 activity is not induced by a decidualization stimulus. In spontaneously cycling female rats, both D2 and D3 were observed to be 3- to 8-fold higher in proestrus, compared with diestrus. Furthermore, levels of D2 and D3 activity were greatly increased in ovariectomized rats given E2 and P in various combinations. D2 activity was stimulated primarily by E2, whereas E2 and P acted synergistically to increase D3 activity. These results demonstrate that E2 and P regulate thyroid hormone metabolism in the uterus, and that the implantation process is a potent stimulus for the induction of D3 activity in this organ. Such precise and profound changes in deiodinase expression are likely to play important physiological roles in fetal development and may influence uterine function.
2型和3型脱碘酶（D2、D3）分别将甲状腺素（T4）转化为活性和非活性代谢产物，在啮齿动物子宫中表达，且在孕期高度诱导表达。为研究调控这些酶在该组织中表达的因素，我们研究了妊娠大鼠、人工诱导蜕膜化前后的假孕大鼠以及用17β-雌二醇（E2）和/或孕酮（P）处理的去卵巢大鼠的D2和D3活性。我们的结果表明，D3活性在着床后立即开始诱导，并在接下来的72小时内显著增加。在假孕大鼠人工蜕膜化的子宫中观察到类似的D3诱导时间进程和幅度，而在同一动物未蜕膜化的对照子宫角中仅观察到活性的最小增加。相反，蜕膜化刺激不会诱导D2活性。在自发周期的雌性大鼠中，与动情间期相比，在动情前期观察到D2和D3均升高3至8倍。此外，给予不同组合E2和P的去卵巢大鼠中，D2和D3活性水平大幅增加。D2活性主要由E2刺激，而E2和P协同作用增加D3活性。这些结果表明，E2和P调节子宫中的甲状腺激素代谢，并且着床过程是该器官中诱导D3活性的有效刺激。脱碘酶表达的这种精确而深刻的变化可能在胎儿发育中发挥重要生理作用，并可能影响子宫功能。
