Paternostro M A, Meisami E
Department of Molecular & Integrative Physiology, University of Illinois, Urbana 61801, USA.
Brain Res Dev Brain Res. 1996 Oct 23;96(1-2):173-83. doi: 10.1016/0165-3806(96)00110-1.
Our recent studies have shown that restoration of thyroid function in developing hypothyroid rats results in upregulation of olfactory neurogenesis and compensatory proliferation of olfactory receptor neurons (ORN) in the olfactory epithelium (OE) (Paternostro and Meisami, Dev. Brain Res., 76 (1993) 151-161; ibid., 83 (1994) 151-162). It was not clear, however, whether the newly forming ORNs undergo complete maturational stages. To determine the effects of restoration of thyroid function on maturation of ORNs, the density and total number of mature ORNs were estimated in the OE of euthyroid and hypothyroid rats at postnatal days 1, 12, 25 and 90 and the results were compared with those in rats allowed to recover from early thyroid deficiency at weaning (day 25). As a marker for mature ORNs, and on the basis of one olfactory dendritic knob per ORN, the density and total number of the olfactory knobs were determined in the entire extent of the OE covering the nasal septum. Hypothyroidism was induced by adding propylthiouracil (PTU) to the drinking water (1 g/l) from birth until days 12, 25 or 90 of age. Recovery from hypothyroidism was induced by withdrawal of PTU at day 25, leading to restoration of thyroid function and somatic growth recovery. The density of olfactory knobs was determined in 1 microm semi-thin sections stained with toluidine blue. In the normal rats, the number of olfactory knobs (= mature ORNs) increased 8.5- and 3-fold during postnatal days 1-25 and 25-90 respectively, reaching a mean value of 4 X 10(6)/septal OE, compared to 2.8- and 1.4-fold, respectively, for the hypothyroid rats. This led to deficits of 51% and 76% in the number of mature ORNs in the 25- and 90-day-old hypothyroid rats. In rats allowed to recover, the number of mature ORNs increased 4.5-fold during postnatal days 25-90 (3 X > hypothyroid rats and 1.5 X > controls). The results indicate marked upregulation of the maturational process of the ORNs and their compensatory accretion within the OE of the recovery group. The recovery process was not complete however, as indicated by a remaining deficit of about 25% in the total number of mature ORN, compared to normal 90-day controls. Thus thyroid hormones are essential for accretion of new mature ORNs in both the suckling and postweaning rats. Also, the ORNs show a remarkable ability to recover from severe early hypothyroid-induced growth retardation and attain normal mature state.
我们最近的研究表明，在发育中的甲状腺功能减退大鼠中恢复甲状腺功能会导致嗅觉神经发生上调，以及嗅上皮（OE）中嗅觉受体神经元（ORN）的代偿性增殖（Paternostro和Meisami，《发育脑研究》，76（1993）151 - 161；同上，83（1994）151 - 162）。然而，尚不清楚新形成的ORN是否经历完整的成熟阶段。为了确定甲状腺功能恢复对ORN成熟的影响，在出生后第1、12、25和90天，对甲状腺功能正常和甲状腺功能减退大鼠的OE中成熟ORN的密度和总数进行了估计，并将结果与在断奶时（第25天）从早期甲状腺功能减退中恢复的大鼠进行了比较。作为成熟ORN的标志物，基于每个ORN有一个嗅觉树突小球，在覆盖鼻中隔的整个OE范围内确定嗅觉小球的密度和总数。从出生到12、25或90日龄，通过在饮用水中添加丙硫氧嘧啶（PTU）（1 g/l）诱导甲状腺功能减退。在第25天停用PTU诱导甲状腺功能减退的恢复，导致甲状腺功能恢复和体细胞生长恢复。在甲苯胺蓝染色的1微米半薄切片中测定嗅觉小球的密度。在正常大鼠中，出生后第1 - 25天和25 - 90天期间，嗅觉小球（=成熟ORN）的数量分别增加了8.5倍和3倍，达到平均4×10⁶/鼻中隔OE，相比之下，甲状腺功能减退大鼠分别增加了2.8倍和1.4倍。这导致25日龄和90日龄甲状腺功能减退大鼠中成熟ORN数量分别减少了51%和76%。在恢复的大鼠中，出生后第25 - 90天期间成熟ORN的数量增加了4.5倍（比甲状腺功能减退大鼠多3倍，比对照组多1.5倍）。结果表明，恢复组的ORN成熟过程明显上调，且在OE内有代偿性增加。然而，恢复过程并不完整，与正常90日龄对照组相比，成熟ORN总数仍有大约25%的不足。因此，甲状腺激素对于哺乳期和断奶后大鼠中新的成熟ORN的增加至关重要。此外，ORN显示出从严重的早期甲状腺功能减退诱导的生长迟缓中恢复并达到正常成熟状态的显著能力。
