Inflammation and epithelial alterations in rat prostate: impact of the androgen to oestrogen ratio.
Chronic non-bacterial prostatitis may offer new insights into the pathogenesis of human benign prostatic hyperplasia and prostate cancer and the strategies for their treatment and prevention. The potential significance of androgen replacement therapy in terms of the reversal of oestradiol (E(2))-induced inflammatory reaction was studied in the dorsolateral prostate (DLP) of the Noble rat. Castrated Noble rats were treated with E(2) and different doses of androgens [dihydrotestosterone (DHT) and testosterone (T)] to achieve an elevated concentration of E(2) and a wide range of the androgen-to-oestradiol ratios in serum. After the 3-week treatment, inflammatory changes in the DLP were classified and counted. Oestrogen receptor alpha (ER alpha), progesterone receptor (PR), fos-related antigen-2 (Fra2), Ki-67 and P63 were immunocytochemically stained. T, E(2) and prolactin concentrations in serum were measured and the relative weights of the seminal vesicles and pituitary glands and microscopic structures of the DLP and seminal vesicle ducts were determined. Hypoandrogenic doses of DHT (judged on the basis of seminal vesicle weight gain), dose-dependently increased the number of perivascular and stromal inflammatory infiltrates. T and DHT were anti-inflammatory at the doses which normalized or over stimulated the growth of the seminal vesicles. As signs of anti-oestrogenicity, androgens dose-dependently decreased the number and distribution of the ER alpha and PR-positive cells at proinflammatory concentrations. Anti-inflammatory concentrations were needed to reduce the expression of Fra2, E(2)-increased prolactin concentration in serum and pituitary weight. The androgen concentrations required to prevent proinflammatory and epithelial responses to E(2) in the presence of elevated E(2) concentrations may subject the accessory sex glands to more intense androgenic stimulation than is normal for the male. The androgen-resistant endpoints of oestrogen action (body weight reduction and hyperplasia of seminal vesicle ducts) further indicate limitations in the possible preventive effects of androgen-replacement therapy.
Yatkin
Emrah
E
Department of Cell Biology and Anatomy, Institute of Biomedicine, University of Turku, Turku, Finland. emrah.yatkin@utu.fi
Bernoulli
Jenni
J
Talvitie
Eva-Maria
EM
Santti
Risto
R
D000818:Animals; D013196:Dihydrotestosterone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood; D047628:Estrogen Receptor alpha / Q000378:metabolism; D051921:Fos-Related Antigen-2 / Q000378:metabolism; D020249:Hormone Replacement Therapy; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D009919:Orchiectomy; D009929:Organ Size; D010902:Pituitary Gland / Q000187:drug effects / Q000473:pathology; D011388:Prolactin / Q000097:blood; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011472:Prostatitis / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D011980:Receptors, Progesterone / Q000378:metabolism; D012669:Seminal Vesicles / Q000187:drug effects / Q000473:pathology; D013739:Testosterone / Q000008:administration & dosage* / Q000097:blood
D004343:Drug Implants; D047628:Estrogen Receptor alpha; D051921:Fos-Related Antigen-2; C497874:Fosl2 protein, rat; D019394:Ki-67 Antigen; D011980:Receptors, Progesterone; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; D011388:Prolactin