Pre- and postnatal testosterone administration induces proliferative epithelial lesions with neuroendocrine differentiation in the dorsal lobe of the rat prostate.
BACKGROUND
Androgens are implicated in the pathogenesis of prostatic carcinoma. We have elucidated the role of pre- and postnatal testosterone administration in the occurrence of proliferative lesions as well as neuroendocrine (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 fetus in the early organogenetic period of the rat prostatic complex. One group of the male offspring was followed without further testosterone treatment; a second group received testosterone only in the pubertal period; a third group was given testosterone from puberty and throughout life (46 weeks). These groups were compared to parallel groups (1A-1C) of male offspring without a testosterone supplement in pregnancy.


RESULTS
The serum testosterone concentrations in the rats receiving testosterone were significantly higher than those of control rats. Histopathologically, the testosterone-induced proliferative lesions, mainly hyperplastic, were almost exclusively located in the dorsal lobe. Chromogranin A-immunoreactive (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 testosterone only in puberty was comparable to the incidence found in those rats receiving testosterone in puberty and throughout life. This finding may have clinical implications for young athletes, who use testosterone as an anabolic drug. The occurrence of CgA-IR cells increased in proliferative lesions in the dorsal lobe of the rat prostatic complex.
Angelsen
A
A
Department of Urology/Surgery, University Hospital of Trondheim, Norway. Anders.Angelsen@medisin.ntnu.no
Falkmer
S
S
Sandvik
A K
AK
Waldum
H L
HL
D000375:Aging; D000818:Animals; D001835:Body Weight; D002454:Cell Differentiation; D004848:Epithelium / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D009490:Neurosecretory Systems / Q000473:pathology*; D009929:Organ Size; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012741:Sexual Maturation; D012835:Silver Nitrate; D016622:Silver Staining; D013739:Testosterone / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*
D013739:Testosterone; D012835:Silver Nitrate