Cycling activity of benign prostatic epithelial cells during long-term androgen blockade: evidence for self-renewal of luminal cells.

Combined androgen blockade (CAB) therapy (LHRH agonist and flutamide) for 6 months leads to marked regressive changes of the prostate gland. This is associated with a reduction in the ratio of luminal to basal cells in the peripheral zone (PZ) in hyperplastic glands of the transitional zone (TZ). To examine the cycling activity of luminal and basal cells, double immunostaining was performed. For precise definition of basal cells, the basal cell-specific antibody 34 beta E12 was used, while cycling cells were identified by the MIB-1 antibody. In 6-month-treated specimens, the fraction of cycling luminal cells increased from 0.3 to 2.5 per cent in the PZ and from 0.2 to 3.9 per cent in the TZ. This was associated with an inversion of the ratio of MIB-1-labelled luminal to basal cells, with values of 5.7:1 (PZ) and 3.9:1 (TZ), compared with 1:4 (PZ) and 1:5 (TZ) in untreated specimens. The predominance continued for at least 11 years of CAB. The findings strongly suggest that luminal cells are capable of self-renewal under conditions of low androgen levels. The substantial decrease of prostatic volume on long-term CAB implies that cell loss outweighs cell proliferation.