Estradiol causes a dose-dependent stimulation of prostate growth in castrated beagle dogs.
BACKGROUND
Previous studies have shown that chronic treatment of castrate dogs with androgen and estrogen results in significant prostate growth. Estrogen treatment of castrate dogs in the absence of androgen has resulted in conflicting data as reported by several authors. The purpose of this experiment was to evaluate the effect of a physiological dose of estradiol on prostate growth in dogs, using ultrasound to study size changes over time.


METHODS
Dogs (n = 25) were randomly divided into groups (n = 5) and treated as follows: castration alone (CC), castration plus low dose estradiol (E(2) low), castration plus high estradiol (E(2) high), castration plus estradiol and androstanediol (E(2)A), or no treatment (normal controls, NC). Silastic implants containing 5alpha-androstan-3alpha-17beta-diol (3alphadiol), and/or 17beta-estradiol were used for continous delivery of steroids. Prostate volume was measured by transrectal ultrasonography, and blood was drawn for hormone and sex hormone binding globulin (SHBG) determinations.


RESULTS
Results show that serum estradiol and SHBG levels were fairly constant over 12 weeks in all groups. Estradiol-treated groups had mean serum estradiol values of approximately 40 and 60 pg/ml, respectively. Initially, all groups had similar prostate volumes. Over 12 weeks the castrate dogs had a decline in prostate volume, whereas the intact dogs and those treated with E(2) and 3alpha-diol maintained a constant prostate volume. Estradiol treatment caused a large, late onset (week 7), dose-dependent increase in prostate volume relative to the intact group (P < 0.01). At 12 weeks, animals were euthanized and prostates weighed. The mean prostate weights in each group were: NC 14.8 +/- 2. 9, CC 2.4 +/- 0.5, E(2)A 9.7 +/- 2.0, E(2) low 21.7 +/- 4.3, and E(2) high 63.6 +/- 12.6 g (geometric mean +/- SEM). Histologically, prostates of estrogen-treated dogs showed metaplastic squamous epithelium.


CONCLUSIONS
These results demonstrate that estradiol causes marked dose-dependent stimulation of prostate growth in the castrate dog.
Rhodes
L
L
Department of Clinical Development, Merial Ltd., Iselin, New Jersey, USA.
Ding
V D
VD
Kemp
R K
RK
Khan
M S
MS
Nakhla
A M
AM
Pikounis
B
B
Rosner
W
W
Saunders
H M
HM
Feeney
W P
WP
D045930:Anabolic Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D015113:Androstane-3,17-diol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D013196:Dihydrotestosterone / Q000097:blood; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D006651:Histocytochemistry; D008297:Male; D009919:Orchiectomy / Q000662:veterinary; D011467:Prostate / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000254:growth & development; D011897:Random Allocation; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood; D014463:Ultrasonography
D045930:Anabolic Agents; D004343:Drug Implants; D012738:Sex Hormone-Binding Globulin; D013196:Dihydrotestosterone; D015113:Androstane-3,17-diol; D013739:Testosterone; D004958:Estradiol