Näntö-Salonen K, Muller H L, Hoffman A R, Vu T H, Rosenfeld R G
Department of Pediatrics, Stanford University Medical Center, California 94305.
Endocrinology. 1993 Feb;132(2):781-8. doi: 10.1210/endo.132.2.7678799.
Normal somatic growth requires that both the thyroid hormone axis and GH axis be intact. Thyroid hormone stimulates GH secretion, and many thyroid hormone actions on the insulin-like growth factor (IGF) system can be explained by this mechanism. We have previously described distinct changes in IGF binding protein (IGFBP) expression in experimental hypothyroidism in the rat; these changes could be completely corrected by thyroid hormone replacement. To see if the effects of thyroid hormone on IGFBP expression are, in fact, indirect GH effects, we rendered both newborn and adult rats hypothyroid with methimazole treatment, and investigated whether we could correct the resulting IGF and IGFBP changes with GH replacement. The prolonged high expression of serum IGFBP-2 and liver IGFBP-2 messenger RNA (mRNA) during the perinatal period in hypothyroid rat pups could not be normalized by GH therapy, although serum IGF-I values (reduced to 54% of control levels in the hypothyroid animals) were brought up to control level. In adult hypothyroid rats, serum IGF-I concentrations (51% of control levels), were increased up to 79% of control levels, but not totally corrected, by GH therapy. Reduced IGFBP-3 expression (80% of control serum and 50% of control liver mRNA levels) in adult hypothyroid animals was normalized by GH, but there was no correction of the reduced IGFBP-4 serum levels (50% of control levels). Hepatic mRNA levels for the type 1 and 2 IGF receptors were not altered by hypothyroidism, or by thyroid or GH replacement. Somatic growth in hypothyroid pups and adults was only partially corrected by GH therapy. We conclude that GH treatment of hypothyroid animals normalized serum IGF-I levels in the hypothyroid rat pup, but did not correct their prolonged IGFBP-2 expression. In the mature animal, serum IGF-I levels were partially corrected and IGFBP-3 levels were normalized by GH, but no change could be induced in the reduced serum IGFBP-4 levels. All the above changes were normalized by thyroid hormone replacement. Thus, the effects of thyroid hormone on serum IGF levels and IGFBP-3 expression seem to be mediated indirectly via GH. The effects on IGFBP-2 ontogeny, and IGFBP-4 expression in the mature animal, however, are either direct thyroid hormone effects, or mediated by some other route, independent of GH, IGFs, or IGF receptors.
正常的体细胞生长要求甲状腺激素轴和生长激素（GH）轴均保持完整。甲状腺激素刺激GH分泌，甲状腺激素对胰岛素样生长因子（IGF）系统的许多作用都可以用这一机制来解释。我们之前已经描述了大鼠实验性甲状腺功能减退时IGF结合蛋白（IGFBP）表达的明显变化；这些变化可以通过甲状腺激素替代完全纠正。为了确定甲状腺激素对IGFBP表达的影响实际上是否是GH的间接作用，我们用甲巯咪唑处理新生和成年大鼠使其甲状腺功能减退，并研究是否能用GH替代来纠正由此导致的IGF和IGFBP变化。尽管甲状腺功能减退大鼠幼崽围生期血清IGFBP - 2和肝脏IGFBP - 2信使核糖核酸（mRNA）的持续高表达不能通过GH治疗恢复正常，但血清IGF - I值（甲状腺功能减退动物降至对照水平的54%）被提高到了对照水平。在成年甲状腺功能减退大鼠中，血清IGF - I浓度（对照水平的51%）通过GH治疗提高到了对照水平的79%，但未完全纠正。成年甲状腺功能减退动物中降低的IGFBP - 3表达（对照血清的80%和对照肝脏mRNA水平的50%）通过GH恢复正常，但降低的IGFBP - 4血清水平（对照水平的50%）未得到纠正。1型和2型IGF受体的肝脏mRNA水平不受甲状腺功能减退、甲状腺激素或GH替代的影响。甲状腺功能减退幼崽和成年动物的体细胞生长仅通过GH治疗得到部分纠正。我们得出结论，对甲状腺功能减退动物进行GH治疗可使甲状腺功能减退大鼠幼崽的血清IGF - I水平恢复正常，但不能纠正其持续的IGFBP - 2表达。在成年动物中，血清IGF - I水平得到部分纠正，IGFBP - 3水平通过GH恢复正常，但降低的血清IGFBP - 4水平未发生变化。上述所有变化通过甲状腺激素替代均恢复正常。因此，甲状腺激素对血清IGF水平和IGFBP - 3表达的影响似乎是通过GH间接介导的。然而，对IGFBP - 2个体发育以及成年动物中IGFBP - 4表达的影响，要么是甲状腺激素的直接作用，要么是由其他途径介导的，独立于GH、IGF或IGF受体。
