Baron J, Klein K O, Colli M J, Yanovski J A, Novosad J A, Bacher J D, Cutler G B
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Endocrinology. 1994 Oct;135(4):1367-71. doi: 10.1210/endo.135.4.7925098.
In humans and other mammals, the release from growth-inhibiting conditions, such as glucocorticoid excess, leads to supranormal linear growth. The prevailing explanation for this catch-up growth involves a central nervous system mechanism that compares actual body size to an age-appropriate set-point and adjusts growth rate accordingly via a circulating factor. Although such a neuroendocrine "sizostat" was hypothesized more than 30 yr ago, its existence has never been confirmed experimentally. Here we show that suppression of growth within a single growth plate by locally administered glucocorticoid is followed by local catch-up growth that is restricted to the affected growth plate. Thus, the catch-up growth cannot be explained by neuroendocrine mechanism but, rather, must arise from a mechanism intrinsic to the growth plate. To explain this finding, we propose that the normal senescent decline in growth plate function depends not on age per se, but on the cumulative number of stem cell divisions, and that glucocorticoid administration, by suppressing stem cell proliferation, delays senescence, resulting in catch-up growth after the growth-inhibiting agent is removed.
在人类和其他哺乳动物中，从生长抑制状态（如糖皮质激素过量）中释放出来会导致超常的线性生长。对于这种追赶性生长的普遍解释涉及一种中枢神经系统机制，该机制将实际身体大小与适合年龄的设定点进行比较，并通过一种循环因子相应地调整生长速率。尽管这种神经内分泌“大小调节器”在30多年前就已被提出，但其实验存在性从未得到证实。在这里，我们表明，局部施用糖皮质激素对单个生长板内生长的抑制之后会出现仅限于受影响生长板的局部追赶性生长。因此，追赶性生长不能用神经内分泌机制来解释，而必须源于生长板固有的一种机制。为了解释这一发现，我们提出生长板功能的正常衰老下降并非取决于年龄本身，而是取决于干细胞分裂的累积数量，并且糖皮质激素的施用通过抑制干细胞增殖来延迟衰老，从而在生长抑制因子被去除后导致追赶性生长。
