Direct response of the murine prostate gland and seminal vesicles to estradiol.
In the prostate, testosterone action depends on conversion to bioactive metabolites dihydrotestosterone and 17beta-estradiol (E2) via the 5alpha-reductase and aromatase enzymes, respectively. Exogenous estrogen inhibits prostate growth by indirect effects caused by suppression of pituitary gonadotropins and testicular testosterone output, but direct effects are less well known. Direct effects of estrogens were evaluated using the hypogonadal (hpg) mouse model, which has postnatal deficiency in gonadotropins and testosterone but remains hormone sensitive. Mature hpg mice were implanted sc with implants filled with E2. After 6 wk, prostate lobe [anterior prostate (AP) and ventral prostate (VP)] and seminal vesicle (SV) organ volumes were significantly increased (P < 0.05) but remained smaller than wild-type mice. Analysis of the relative volumes (the proportional composition) of each tissue compartment in these organs showed significant increases in cellular and luminal volumes (P < 0.05) in AP (but not VP) and in SVs. Stromal fibroblasts proliferated, whereas smooth muscle cells were reduced in the AP and SVs. In the epithelia, basal cells proliferated and became metaplastic in the AP and VP. In the AP, luminal debris accumulated, together with an inflammatory response, but there was no evidence of malignant changes. The current study unequivocally demonstrates direct proliferative responses to E2 in the hpg mouse AP and VP lobes and SVs, characterized by discrete lobe-specific changes, including smooth-muscle regression, fibroblast proliferation, inflammation, and basal epithelial cell proliferation and metaplasia.
Bianco
Joseph John
JJ
Centre for Urological Research, Monash University, Clayton, Victoria, 3168, Australia.
Handelsman
David J
DJ
Pedersen
John Stuart
JS
Risbridger
Gail Petuna
GP
D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D015820:Cadherins / Q000032:analysis; D002455:Cell Division; D002467:Cell Nucleus / Q000737:chemistry; D004343:Drug Implants; D004847:Epithelial Cells / Q000473:pathology; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D005347:Fibroblasts / Q000473:pathology; D007006:Hypogonadism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009130:Muscle, Smooth / Q000473:pathology; D011467:Prostate / Q000187:drug effects* / Q000473:pathology; D011960:Receptors, Estrogen / Q000032:analysis; D012669:Seminal Vesicles / Q000187:drug effects* / Q000473:pathology; D017154:Stromal Cells / Q000473:pathology
D015820:Cadherins; D004343:Drug Implants; D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D004958:Estradiol