Viticchi C, Basso A, Grinta R, Piantanelli L
Center of Biochemistry, Gerontologic Research Department INRCA, Ancona, Italy.
Gerontology. 1997;43(5):268-76. doi: 10.1159/000213862.
Up-regulation of brain cortex beta-adrenoceptors (beta ARs) can be induced by very acute stimulation with a single injection of T4 or T3 in young Balb/c-nu mice. We have also shown that this very rapid receptor increase can also be demonstrated in ageing animals when stimulated with T3 but not T4 injection. The aim of the present paper was to verify the capability of the thymus to reverse these impairments which we often observed in other experiments on old mice and young athymic nudes. The up-regulation induced by T4 and T3 was studied in normal and athymic nude young, normal old, and normal old and athymic nude young mice grafted with neonatal thymus 1 month earlier. In addition, since brain cortex bears both beta AR subpopulations, the eventual differential behavior of beta 1AR and beta 2AR subtypes was also investigated. Animals were injected intraperitoneally with saline, or saline containing 0.5 microgram T3 or 6.4 micrograms T4 per g body weight and killed 15 or 60 min after injection. Results show that thymus can recover the modifications of basal levels as well as T3-induced up-regulation of beta ARs in nude and old mice. On the contrary, impaired response to T4 stimulation is corrected in nude but not in old mice. The peripheral conversion of T4 into T3 can explain their differential influence since a correct conversion only occurs in presence of an efficient beta-adrenergic function. Thus, a vicious circle may occur with a decreasing number of beta-adrenoceptors causing in old age altered T4 to T3 conversion, in turn responsible for altered beta-adrenergic responsiveness to T4.
在年轻的Balb/c-nu小鼠中，单次注射T4或T3进行非常急性的刺激可诱导大脑皮质β-肾上腺素能受体（β-ARs）上调。我们还表明，当用T3而非T4注射刺激时，这种非常快速的受体增加在衰老动物中也能得到证实。本文的目的是验证胸腺逆转这些损伤的能力，这些损伤我们在其他关于老年小鼠和年轻无胸腺裸鼠的实验中经常观察到。在正常和无胸腺裸鼠幼龄、正常老龄以及1个月前移植了新生胸腺的正常老龄和无胸腺裸鼠幼龄小鼠中，研究了T4和T3诱导的上调情况。此外，由于大脑皮质同时存在两种β-AR亚群，还研究了β1AR和β2AR亚型最终的差异行为。给动物腹腔注射生理盐水，或每克体重含0.5微克T3或6.4微克T4的生理盐水，并在注射后15或60分钟处死。结果表明，胸腺可以恢复裸鼠和老龄小鼠基础水平的改变以及T3诱导的β-ARs上调。相反，对T4刺激的受损反应在裸鼠中得到纠正，但在老龄小鼠中未得到纠正。T4向T3的外周转化可以解释它们的差异影响，因为只有在有效的β-肾上腺素能功能存在时才会发生正确的转化。因此，可能会出现一个恶性循环，β-肾上腺素能受体数量减少导致老年时T4向T3的转化改变，进而导致对T4的β-肾上腺素能反应性改变。
