Meeker A K, Sommerfeld H J, Coffey D S
The James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-2101, USA.
Endocrinology. 1996 Dec;137(12):5743-6. doi: 10.1210/endo.137.12.8940411.
Telomeres, the repetitive non-coding DNA sequences found at the ends of all eukaryotic chromosomes, shorten with each cell division. It has been proposed that telomere shortening may be the counting element of a mitotic clock that keeps track of cell divisions; with shortening to a critical length acting as a senescence signal underlying cellular aging. The enzyme telomerase functions to maintain telomere length, thus allowing unlimited cell division, and has been associated with cellular immortalization and cancer. Stem cells have large, perhaps unlimited, replicative capacities. Since these cells are potentially immortal, we reasoned that they might posses active telomerase. We therefore assayed for telomerase activity in the stem cell enriched pools of the androgen-depleted sex accessory tissues in the castrated male rat. Following castration, the ventral prostate and seminal vesicles of the rat involute, losing approximately 90% of their cells by 21 days. These residual glands persist, and are enriched for stem cells, being capable of fully regenerating these glands if testosterone is re-introduced into the animal. We assayed telomerase activity in extracts from normal, involuted, and regenerating ventral prostate and seminal vesicles. Normal glands were found to be telomerase negative, whereas telomerase activity appeared as these glands involuted following castration. Conversely, telomerase activity disappeared during testosterone-induced regeneration of these residual glands. These results provide strong evidence for the ability of androgen to negatively-regulate telomerase activity in stem cell populations of the rat ventral prostate and seminal vesicles. and represent the first in vivo model system for the modulation of telomerase activity.
端粒是在所有真核染色体末端发现的重复非编码DNA序列，其长度会随着细胞的每次分裂而缩短。有人提出，端粒缩短可能是有丝分裂时钟的计数元件，用于记录细胞分裂次数；当缩短到临界长度时，可作为细胞衰老的衰老信号。端粒酶的功能是维持端粒长度，从而允许细胞无限分裂，并且与细胞永生化和癌症相关。干细胞具有强大的、或许是无限的复制能力。由于这些细胞具有潜在的永生性，我们推测它们可能拥有活跃的端粒酶。因此，我们检测了去势雄性大鼠雄激素缺乏的性附属组织中富含干细胞的细胞池中的端粒酶活性。去势后，大鼠的腹侧前列腺和精囊会 involute，到21天时大约失去90%的细胞。这些残留腺体持续存在，并且富含干细胞，如果将睾酮重新引入动物体内，它们能够使这些腺体完全再生。我们检测了正常、involuted和再生的腹侧前列腺及精囊提取物中的端粒酶活性。发现正常腺体的端粒酶呈阴性，而在去势后这些腺体involute时端粒酶活性出现。相反，在睾酮诱导这些残留腺体再生的过程中，端粒酶活性消失。这些结果为雄激素对大鼠腹侧前列腺和精囊干细胞群体中端粒酶活性进行负调控的能力提供了有力证据，并且代表了第一个用于调节端粒酶活性的体内模型系统。 （注：原文中involute这个词在生物学语境下不好直接准确翻译，根据上下文推测这里可能是萎缩、退化之类的意思，但不确定准确含义，所以保留原文未翻译。）
