TELOMERASE IS ACTIVATED IN THE PROSTATE AND SEMINAL-VESICLES OF THE CASTRATED RAT

Telomeres, the repetitive non-coding DNA sequences found at the ends o f 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 a ging. The enzyme telomerase functions to maintain telomere length thus allowing unlimited cell division, and has been associated with cellul ar immortalization and cancer. Stem cells have large, perhaps unlimite d, replicative capacities. Since these cells are potentially immortal, we reasoned that they might posses active telomerase. We therefore as sayed for telomerase activity in the stem cell enriched pools of the a ndrogen-depleted sex accessory tissues in the castrated male rat. Foll owing castration, the ventral prostate and seminal vesicles of the rat involute, losing approximately 90% of their cells by 21 days. These r esidual glands persist, and are enriched for stem cells, being capable of fully regenerating these glands if testosterone is re-introduced i nto the animal. We assayed telomerase activity in extracts from normal , involuted, and regenerating ventral prostate and seminal vesicles. N ormal glands were found to be telomerase negative, whereas telomerase activity appeared as these glands involuted following castration. Conv ersely, telomerase activity disappeared during testosterone-induced re generation of these residual glands. These results provide strong evid ence for the ability of androgen to negatively-regulate telomerase act ivity in stem cell populations of the rat ventral prostate and seminal vesicles, and represent the first in vivo model system for the modula tion of telomerase activity.