Gresik E W, Wenk-Salamone K, Onetti-Muda A, Gubits R M, Shaw P A
Mech Ageing Dev. 1986 Apr;34(2):175-89. doi: 10.1016/0047-6374(86)90033-3.
We have compared the responsiveness of the submandibular glands of mature (12 month old) and senescent (26-28 month old) male C57BL/6 mice to dihydrotestosterone (DHT) or triiodothyronine (T3) in terms of steady state levels of epidermal growth factor (EGF) protein and EGF mRNA. Northern blot analyses did not disclose any differences with age in the apparent sizes of EGF mRNA species. In untreated animals, submandibular glands of 26-28-month-old mice contained approximately 50% less EGF, and 75% less EGF mRNA than those of 12-month-old males. With advanced age, there was a 20% reduction in the absolute volume of the granular convoluted tubule (GCT) compartment, which is the exclusive site of EGF and EGF mRNA in the gland. In general, GCTs of old mice were composed of smaller cells with fewer secretion granules, but there was considerable cell-to-cell variation. In addition, there was greater variation in the intensity of immunocytochemical staining for EGF in senescent GCT cells, which also gave a lower and more variable in situ hybridization signal for EGF mRNA. After hormonal stimulation for 1 week with either tri-iodothyronine (T3) or dihydrotestosterone (DHT), EGF protein concentration in the glands was induced to the same level at both ages. However, EGF mRNA was 50% less abundant in old hormonally stimulated glands, compared to similarly treated young ones. Although many GCT cells in treated glands of senescent males respond to hormonal stimulation by increases in size and in content of secretion granules, there was cell-to-cell variation in responsiveness, especially after treatment with T3. These findings indicate that the decreases seen in the entire gland in EGF and EGF mRNA are caused by a wide-spread deterioration of the GCT cells themselves, which apparently can be reversed in many but not all GCT cells by stimulation with supraphysiologic doses of either T3 or DHT.
我们比较了成熟（12个月大）和衰老（26 - 28个月大）的雄性C57BL/6小鼠下颌下腺对二氢睾酮（DHT）或三碘甲状腺原氨酸（T3）的反应，检测指标为表皮生长因子（EGF）蛋白和EGF mRNA的稳态水平。Northern印迹分析未发现EGF mRNA种类的表观大小随年龄有任何差异。在未经处理的动物中，26 - 28个月大小鼠的下颌下腺中EGF含量比12个月大的雄性小鼠少约50%，EGF mRNA少75%。随着年龄增长，颗粒曲管（GCT）部分的绝对体积减少了20%，而GCT是腺体中EGF和EGF mRNA的唯一产生部位。一般来说，老年小鼠的GCT由较小的细胞组成，分泌颗粒较少，但细胞间存在相当大的差异。此外，衰老GCT细胞中EGF免疫细胞化学染色强度的变化更大，其EGF mRNA的原位杂交信号也更低且更易变。用三碘甲状腺原氨酸（T3）或二氢睾酮（DHT）激素刺激1周后，两个年龄段腺体中的EGF蛋白浓度均被诱导至相同水平。然而，与同样处理的年轻腺体相比，老年激素刺激腺体中的EGF mRNA丰度低50%。尽管老年雄性小鼠经处理的腺体中的许多GCT细胞对激素刺激有反应，表现为细胞大小和分泌颗粒含量增加，但反应存在细胞间差异，尤其是在用T3处理后。这些发现表明，整个腺体中EGF和EGF mRNA的减少是由GCT细胞自身广泛的退化引起的，超生理剂量的T3或DHT刺激显然可以使许多但并非所有GCT细胞的这种退化得到逆转。
