LNCaP cells represent a useful tool to explore the mechanism of sex hormone action on cell proliferation in an “in culture-in animal” model. Results indicated that: (a) these cells were inhibited from proliferating for extended periods (up to 30 days) when placed in charcoal-dextran-stripped sera; they remained, however, viable because they proliferated when sex hormones were added to this medium; (b) the inhibitory effect of sera was reversed by the addition of 5α-dihydrotestosterone at 3 × 10-10m, 17β-estradiol at 3 × 10-8m and higher concentrations, and progesterone at 3 × 10-10m and higher concentrations; (c) while the dose response to androgens was biphasic (i.e., 5α-dihydrotestosterone at concentrations higher than 3 × 10-10m resulted in progressively lower cell yields), estrogens and progestagens exhibited a monophasic pattern; (d) these cells were exceedingly sensitive to the nutritional environment in which they grew; (e) while these cells have androgen receptors (68 fmol/mg protein; Kd = 2 × 10-9m), estrogen and progestagen receptors could not be detected by biochemical and immunocytochemical techniques; (f) tumors grew at the site of inoculation in castrated nude mice carrying 17β-estradiol and progesterone pellets and in intact male nude mice implanted with placebo pellets, while tumors did not grow in castrated nude mice implanted with a 5α-dihydrotestosterone pellet. Taken together the data collected are compatible with the following conclusions: (a) the proliferative response in LNCaP cells seems not to be directly mediated by their intracellular androgen receptors; (b) plasma-borne trypsin-sensitive inhibitors of the proliferation of these cells (androcolyone I) appear to play a significant role in the proliferative event; (c) natural and synthetic androgens, estrogens, and progestagens cancelled the inhibition by charcoal-dextran-stripped human sera; (d) only androgens were able to trigger an inhibition of cell proliferation (shutoff effect) at concentrations higher than those that affected maximal cell yields (direct negative hypothesis); and (e) a faulty shutoff response is probably a crucial event for the tumorigenesis of these human prostate cells.


This work was supported in part by Grants USPHS NIH CA13410 and NSF DCB8711746.

This content is only available via PDF.