CONSTITUTIVE TELOMERASE ACTIVITY IN CELLS WITH TISSUE-RENEWING POTENTIAL FROM ESTROGEN-REGULATED RAT-TISSUES

To investigate the role of telomerase in estrogen-regulated rodent tis sues, we assayed the activity levels of this enzyme and measured cell proliferation and indicators of cellularity in vagina, mammary gland, and uterus from virgin, pregnant, ovariectomized, and ovariectomized e stradiol-treated rats. No association was observed between telomerase activity and increased cell proliferation. Telomerase activity was sig nificantly higher (P=0.003) in vagina obtained from ovariectomized rat s (very low proliferation) than in vagina from ovariectomized and estr adiol-treated rats (high proliferation, high differentiation). The hig h telomerase levels observed in vagina from ovariectomized rats indica tes that the same epithelial compartment (i.e., basal layer) that has the potential to reconstitute the epithelium also contains the cells t hat express telomerase. The lower telomerase activity in the keratiniz ed (differentiated) vagina was probably due to dilution of the number of telomerase-producing cells by the terminally differentiated non-tel omerase-producing cells. Similar results were observed in uterus from ovariectomized ver sus ovariectomized and estradiol-treated rats. Telo merase activity was highest in uterus from pregnant rats. Telomerase l evels in samples from total mammary gland fat pads varied considerably between groups and appeared to be representative of the amount of epi thelium present in the sample. Interestingly, when mammary gland sampl es from the same animals were obtained from pure epithelial organoid p reparations, no differences in telomerase activity could be distinguis hed between animals or groups. Overall these data suggest that telomer ase activity, particularly in rat vagina and uterus, appears to be ass ociated with a cell subpopulation showing proliferative and tissue rec onstitution potential and not directly associated with proliferation s tatus per se.