Telomerase is activated in the prostate and seminal vesicles of the castrated rat.

Abstract

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.

Wild‐type but not mutant androgen receptor inhibits expression of the hTERT telomerase subunit: a novel role of AR mutation for prostate cancer development

“…Furthermore, androgen treatment of castrated animals reversed this effect and led to downregulation of telomerase activity (23). These data suggest not only that telomerase activity is repressed by androgens and that reducing androgen levels leads to its activation but also that cancer cells may overcome this repression.…”

“…Interestingly, and in line with the role of androgens as a protective agent, androgen ablation in animal model systems led to induction of telomerase activity (8,22,23). Furthermore, androgen treatment of castrated animals reversed this effect and led to downregulation of telomerase activity (23).…”

Prevention of critical telomere shortening by oestradiol in human normal hepatic cultured cells and carbon tetrachloride induced rat liver fibrosis

“…[26][27][28][29][30][31] Testosterone is a negative regulator of TA. Meeker and colleagues 31 demonstrated that TA is activated in the prostate and seminal vesicles of castrated male rats.…”

“…Meeker and colleagues 31 demonstrated that TA is activated in the prostate and seminal vesicles of castrated male rats. 31 hTERT is upregulated by direct interaction with activated OR. 26 Although the molecular mechanisms of the action of oestradiol have been well studied in HSC, those on hepatocytes have been unclear even though they have high affinity, low capacity, saturable, and specific OR.…”

“…Some indirect and direct evidence has been documented for a possible association between hormonal systems and telomere length. [26][27][28][29][30][31] It is well known that administration of exogenous oestradiol suppresses the progression of hepatic fibrosis and decreases serum levels of hepatic transaminase. 15 22 Oestradiol downregulates the release of extracellular matrix components and fibrosis implementing factors in HSCs.…”