Pre- and postnatal testosterone administration induces proliferative epithelial lesions with neuroendocrine differentiation in the dorsal lobe of therat prostate

BACKGROUND. Androgens are implicated in the pathogenesis of prostatic carci noma. We have elucidated the role of pre- and postnatal testosterone admini stration in the occurrence of proliferative lesions as well as neuroendocri ne (NE) cells in the rat prostatic complex. METHODS. Female rats were given a single dose of 9 mg testosterone enantate i.m. on day 15 of pregnancy; it gave a high testosterone exposure to the f etus in the early organogenetic period of the rat prostatic complex. One gr oup of the male offspring was followed without further testosterone treatme nt; a second group received testosterone only in the pubertal period; a thi rd group was given testosterone from puberty and throughout Life (46 weeks) . These groups were compared to parallel groups (1A-1C) of male offspring w ithout a testosterone supplement in pregnancy. RESULTS. The serum testosterone concentrations in the rats receiving testos terone were significantly higher than those of control rats. Histopathologi cally, the testosterone-induced proliferative lesions, mainly hyperplastic, were almost exclusively located in the dorsal lobe. Chromogranin A-immunor eactive (CgA-IR) cells were rarely found normally, but occurred more often in the proliferative lesions (P < 0.001). CONCLUSIONS. The incidence of proliferative lesions in rats exposed to test osterone only in puberty was comparable to the incidence found in those rat s receiving testosterone in puberty and throughout life. This finding may h ave clinical implications for young athletes, who use testosterone as an an abolic drug. The occurrence of CgA-IR cells increased in proliferative lesi ons in the dorsal lobe of the rat prostatic complex. Prostate 40:65-75, 199 9. (C) 1999 Wiley-Liss, Inc.