Donda A, Lemarchand-Béraud T
Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Endocrinology. 1989 Mar;124(3):1305-9. doi: 10.1210/endo-124-3-1305.
Aging is characterized by a decreased secretion of thyroid hormones in rats associated with unchanged plasma TSH suggestive of impairments in the hypothalamo-pituitary-thyroid axis. Since it is known that pituitary T3 is more determinant on TSH secretion than plasma T3, we measured in young (4 months) and old (26 months) male rats the concentration of T3 in the anterior pituitary gland and found that it was similar in young and old animals despite the low circulating levels of thyroid hormones. This was suggestive of age-related differences in the intrapituitary T4 to T3 conversion. We therefore determined the activity of 5'-deiodinase (5'-D, type I and type II) in the adenohypophysis and investigated possible age-related changes in this enzyme activity in peripheral tissues by its determination in the thyroid gland and liver (type I) of young and old rats. Intrapituitary 5'-D activity was increased in old compared to young rats (type I 5'-D: 4.59 +/- 0.13 vs. 2.92 +/- 0.33 pmol rT3/h x mg protein; type II: 0.54 +/- 0.5 vs. 0.21 +/- 0.03 pmol rT3/h x mg protein; P less than 0.001). In contrast, in the thyroid gland and in the liver, type I 5'-D was reduced with age (4.7 +/- 0.6 vs. 7.4 +/- 0.8 and 3.1 +/- 0.4 vs. 5.6 +/- 0.5 nmol rT3/h x mg protein, respectively; P less than 0.01). These data are illustrative of age-related changes in the activity of 5'-D, different according to the tissues in agreement with the known tissue-specific regulation of the 5'-Ds. The reduced activity of 5'-D in the thyroid and liver of old rats is indicative of an impaired thyroid hormones disposal in peripheral tissues with age. In contrast, in the adenohypophysis of old rats, the increase in the activity of 5'-D is similar to that reported in hypothyroid animals and suggests the development with age of an adaptative mechanism in the presence of low circulating thyroid hormones; this mechanism leads to unchanged intrapituitary concentration of T3 and consequently to unaltered plasma levels of TSH in old rats.
衰老的特征是大鼠甲状腺激素分泌减少,同时血浆促甲状腺激素(TSH)水平不变,提示下丘脑-垂体-甲状腺轴存在功能障碍。由于已知垂体中的三碘甲状腺原氨酸(T3)对TSH分泌的决定性作用大于血浆T3,我们测定了年轻(4个月)和年老(26个月)雄性大鼠垂体前叶中T3的浓度,发现尽管甲状腺激素的循环水平较低,但年轻和年老动物的T3浓度相似。这表明垂体内部甲状腺素(T4)向T3的转化存在年龄相关差异。因此,我们测定了腺垂体中5'-脱碘酶(5'-D,I型和II型)的活性,并通过测定年轻和年老大鼠甲状腺和肝脏(I型)中该酶的活性,研究了外周组织中可能存在的与年龄相关的变化。与年轻大鼠相比,年老大鼠垂体内部5'-D的活性增加(I型5'-D:4.59±0.13对2.92±0.33皮摩尔反三碘甲状腺原氨酸/h×毫克蛋白质;II型:0.54±0.5对0.21±0.03皮摩尔反三碘甲状腺原氨酸/h×毫克蛋白质;P<0.001)。相反,在甲状腺和肝脏中,I型5'-D随年龄增长而降低(分别为4.7±0.6对7.4±0.8和3.1±0.4对5.6±0.5纳摩尔反三碘甲状腺原氨酸/h×毫克蛋白质;P<0.01)。这些数据说明了5'-D活性的年龄相关变化,根据组织不同而有所差异,这与已知的5'-D的组织特异性调节一致。年老大鼠甲状腺和肝脏中5'-D活性降低表明随着年龄增长外周组织中甲状腺激素的代谢出现障碍。相反,在年老大鼠的腺垂体中,5'-D活性的增加与甲状腺功能减退动物中报道的情况相似,提示在循环甲状腺激素水平较低的情况下,随着年龄增长会形成一种适应性机制;这种机制导致垂体内部T3浓度不变,从而使年老大鼠的血浆TSH水平保持不变。